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Sample records for antimicrobial photodynamic therapy

  1. Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy.

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    Jeffersson Krishan Trigo Gutierrez

    Full Text Available Curcumin (CUR has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT. However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA and non-parametric (Kruskal-Wallis tests (α = 0.05. CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR.

  2. Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy

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    Trigo Gutierrez, Jeffersson Krishan; Zanatta, Gabriela Cristina; Ortega, Ana Laura Mira; Balastegui, Maria Isabella Cuba; Sanitá, Paula Volpato; Pavarina, Ana Cláudia; Barbugli, Paula Aboud

    2017-01-01

    Curcumin (CUR) has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT). However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP) and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO) as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species) cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA) and non-parametric (Kruskal-Wallis) tests (α = 0.05). CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR. PMID:29107978

  3. Physical and mathematical modeling of antimicrobial photodynamic therapy

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    Bürgermeister, Lisa; López, Fernando Romero; Schulz, Wolfgang

    2014-07-01

    Antimicrobial photodynamic therapy (aPDT) is a promising method to treat local bacterial infections. The therapy is painless and does not cause bacterial resistances. However, there are gaps in understanding the dynamics of the processes, especially in periodontal treatment. This work describes the advances in fundamental physical and mathematical modeling of aPDT used for interpretation of experimental evidence. The result is a two-dimensional model of aPDT in a dental pocket phantom model. In this model, the propagation of laser light and the kinetics of the chemical reactions are described as coupled processes. The laser light induces the chemical processes depending on its intensity. As a consequence of the chemical processes, the local optical properties and distribution of laser light change as well as the reaction rates. The mathematical description of these coupled processes will help to develop treatment protocols and is the first step toward an inline feedback system for aPDT users.

  4. Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

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    Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

    2013-01-01

    Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photostimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT. PMID

  5. A quaternary ammonium modified coumarin derivative for antimicrobial photodynamic therapy

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    Sun, Zhiyuan; Zhou, Shaona; Gu, Ying; Zhao, Yuxia

    2018-02-01

    A new cationic modified coumarin derivative, 7-diethylamino-3-(3-(4-(trimethylbenzenaminium iodide) phenyl) acryloyl)-2H-chromen-2-one (1), was synthesized and characterized by 1H NMR and mass spectra. It had a strong intramolecular charge transfer absorption band around 460 nm with large molar extinction coefficients of 3.94 × 104 M-1 cm-1 in DMF and 3.86 × 104 M-1 cm-1 in PBS, respectively. Moreover, a moderate singlet oxygen quantum yield of 0.16 was obtained for 1 in DMF. Using methylene blue (MB) under a 630 nm laser as reference, the in vitro antimicrobial photodynamic therapy (aPDT) activity of 1 against three strains, gram positive bacteria methicillin-resistant staphylococcus aureus (MRSA), negative bacteria acinetobacter baumannii (A. baumannii) and fungus Candida albicans (C. albicans), was carried out by irradiation with a 457 nm laser. It was shown that 1 had no dark toxicity to these bacteria when its concentration was up to 100 μM, while under the 457 nm laser it could kill them effectively with an over 3 log CFU/ml decrease of the bacterial viability with its concentration up to 5 μM. The aPDT capability of 1 against MRSA and A. baumannii was equivalent to that of MB. For C. albicans, 1 exhibited much better aPDT effect than MB.

  6. Photodynamic antimicrobial therapy in the treatment of denture stomatitis

    International Nuclear Information System (INIS)

    Senna, Andre Machado de

    2012-01-01

    Denture stomatitis (DS), also called chronic atrophic candidiasis, is the most common oral fungal infection in denture wearers. It has a multifactorial etiology, but the presence of Candida spp. biofilm on the denture is considered the most important factor for the establishment of the DS. This study aimed to evaluate the treatment of DS through the use of photodynamic antimicrobial therapy (PAT), mediated by methylene blue. For this purpose, preclinical studies and clinical trials were performed. Simulators prototypes dentures were made of methyl methacrylate polymer to serve as a basis for biofilm growth of the following species of Candida: C. albicans, C. glabrata, C. dubliniensis, C. krusei, C. tropicalis, C. parapsilosis and C. guilliermondii. Methylene blue solution at a concentration of 450 μg/mL was used as a photosensitizer. The prototypes and biofilms were irradiated with a laser of wavelength of 660 nm, potency of 100 mW, for 80 seconds. For the clinical study, subjects were divided into two groups. The first group received conventional treatment based on the use of antifungal Miconazole. The second group received the treatment by PAT. The preclinical results showed that all species of the genus Candida were susceptible to PAT, with a reduction in colonies that ranged from 2.48 to 3.93 log 10 . Clinical outcomes were evaluated for the reduction of colonies of Candida spp. located in the mucosa and in the prosthesis and relative to the improvement of the clinical aspect of the affected mucosa. Both the conventional therapy and PAT were effective in treating DS. There was no significant statistical difference between PAT and conventional treatment for any of the factors evaluated. Thus, it was concluded that PAT is effective in the treatment of denture stomatitis. (author)

  7. The Antimicrobial Photodynamic Therapy in the Treatment of Peri-Implantitis

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    Umberto Romeo

    2016-01-01

    Full Text Available Introduction. The aim of this study is to demonstrate the effectiveness of addition of the antimicrobial photodynamic therapy to the conventional approach in the treatment of peri-implantitis. Materials and Methods. Forty patients were randomly assigned to test or control groups. Patients were assessed at baseline and at six (T1, twelve (T2, and twenty-four (T3 weeks recording plaque index (PlI, probing pocket depth (PPD, and bleeding on probing (BOP; control group received conventional periodontal therapy, while test group received photodynamic therapy in addition to it. Result. Test group showed a 70% reduction in the plaque index values and a 60% reduction in PD values compared to the baseline. BOP and suppuration were not detectable. Control group showed a significative reduction in plaque index and PD. Discussion. Laser therapy has some advantages in comparison to traditional therapy, with faster and greater healing of the wound. Conclusion. Test group showed after 24 weeks a better value in terms of PPD, BOP, and PlI, with an average pocket depth value of 2 mm, if compared with control group (3 mm. Our results suggest that antimicrobial photodynamic therapy with diode laser and phenothiazine chloride represents a reliable adjunctive treatment to conventional therapy. Photodynamic therapy should, however, be considered a coadjuvant in the treatment of peri-implantitis associated with mechanical (scaling and surgical (grafts treatments.

  8. In Vitro Antimicrobial Photodynamic Therapy Against Trichophyton mentagrophytes Using New Methylene Blue as the Photosensitizer.

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    López-Chicón, P; Gulías, Ò; Nonell, S; Agut, M

    2016-11-01

    Antimicrobial photodynamic therapy combines the use of a photosensitizing drug with light and oxygen to eradicate pathogens. Trichophyton mentagrophytes is a dermatophytic fungus able to invade the skin and keratinized tissues. We have investigated the use of new methylene blue as the photosensitizing agent for antimicrobial photodynamic therapy to produce the in vitro inactivation of T mentagrophytes. A full factorial design was employed to optimize the parameters for photoinactivation of the dermatophyte. The parameters studied were new methylene blue concentration, contact time between the photosensitizing agent and the fungus prior to light treatment, and the fluence of red light (wavelength, 620-645nm) applied. The minimum concentration of new methylene blue necessary to induce the death of all T. mentagrophytes cells in the initial suspension (approximate concentration, 10 6 colony forming units per milliliter) was 50μM for a fluence of 81J/cm 2 after a contact time of 10minutes with the photosensitizing-agent. Increasing the concentration to 100μM allowed the fluence to be decreased to 9J/cm 2 . Comparison of our data with other published data shows that the susceptibility of T. mentagrophytes to antimicrobial photodynamic therapy with new methylene blue is strain-dependent. New methylene blue is a photosensitizing agent that should be considered for the treatment of fungal skin infections caused by this dermatophyte. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

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    Carrera, E. T.; Dias, H. B.; Corbi, S. C. T.; Marcantonio, R. A. C.; Bernardi, A. C. A.; Bagnato, V. S.; Hamblin, M. R.; Rastelli, A. N. S.

    2016-12-01

    In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.

  10. The impact of antimicrobial photodynamic therapy on Streptococcus mutans in an artificial biofilm model

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    Schneider, Martin; Kirfel, Gregor; Krause, Felix; Berthold, Michael; Brede, Olivier; Frentzen, Matthias; Braun, Andreas

    2010-02-01

    The aim of the study was to assess the impact of laser induced antimicrobial photodynamic therapy on the viability of Streptococcus mutans cells employing an aritificial biofilm model. Employing sterile chambered coverglasses, a salivary pellicle layer formation was induced in 19 chambers. Streptococcus mutans cells were inoculated in a sterile culture medium. Using a live/dead bacterial viability kit, bacteria with intact cell membranes stain fluorescent green. Test chambers containing each the pellicle layer and 0.5 ml of the bacterial culture were analyzed using a confocal laser scan microscope within a layer of 10 μm at intervals of 1 μm from the pellicle layer. A photosensitizer was added to the test chambers and irradiated with a diode laser (wavelength: 660 nm, output power: 100 mW, Helbo) for 2 min each. Comparing the baseline fluorescence (median: 13.8 [U], min: 3.7, max: 26.2) with the values after adding the photosensitizer (median: 3.7, min: 1.1, max: 9), a dilution caused decrease of fluorescence could be observed (p0.05). The present study indicates that antimicrobial photodynamic therapy can reduce living bacteria within a layer of 10 μm in an artificial biofilm model. Further studies have to evaluate the maximum biofilm thickness that still allows a toxic effect on microorganisms.

  11. Antimicrobial photodynamic therapy combined with conventional endodontic treatment to eliminate root canal biofilm infection.

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    Garcez, Aguinaldo S; Ribeiro, Martha S; Tegos, George P; Núñez, Silvia C; Jorge, Antonio O C; Hamblin, Michael R

    2007-01-01

    To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-micro fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (Ptreatment. Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. (c) 2006 Wiley-Liss, Inc.

  12. Antimicrobial effects of photodynamic therapy on patients with necrotic pulps and periapical lesion.

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    Garcez, Aguinaldo Silva; Nuñez, Silvia Cristina; Hamblin, Michael R; Ribeiro, Martha Simões

    2008-02-01

    This study analyzed the antimicrobial effect of photodynamic therapy (PDT) in association with endodontic treatment. Twenty patients were selected. Microbiological samples were taken after accessing the canal, endodontic therapy, and PDT. At the end of the first session, the root canal was filled with Ca(OH)(2), and after 1 week, a second session of the therapies was performed. Endodontic therapy gave a mean reduction of 1.08 log. The combination with PDT significantly enhanced the reduction (1.83 log, p = 0.00002). The second endodontic session gave a similar diminution to the first (1.14 log), and the second PDT was significantly more effective than the first (p = 0.002). The second total reduction was significantly higher than the second endodontic therapy (p = 0.0000005). The total first + second reduction (3.19 log) was significantly different from the first combination (p = 0.00006). Results suggest that the use of PDT added to endodontic treatment leads to an enhanced decrease of bacterial load and may be an appropriate approach for the treatment of oral infections.

  13. Adjunctive Application of Antimicrobial Photodynamic Therapy in Nonsurgical Periodontal Treatment: A Review of Literature

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    Takeshi Kikuchi

    2015-10-01

    Full Text Available Periodontal disease is caused by dental plaque biofilms, and the removal of these biofilms from the root surface of teeth plays a central part in its treatment. The conventional treatment for periodontal disease fails to remove periodontal infection in a subset of cases, such as those with complicated root morphology. Adjunctive antimicrobial photodynamic therapy (aPDT has been proposed as an additional treatment for this infectious disease. Many periodontal pathogenic bacteria are susceptible to low-power lasers in the presence of dyes, such as methylene blue, toluidine blue O, malachite green, and indocyanine green. aPDT uses these light-activated photosensitizer that is incorporated selectively by bacteria and absorbs a low-power laser/light with an appropriate wavelength to induce singlet oxygen and free radicals, which are toxic to bacteria. While this technique has been evaluated by many clinical studies, some systematic reviews and meta-analyses have reported controversial results about the benefits of aPDT for periodontal treatment. In the light of these previous reports, the aim of this review is to provide comprehensive information about aPDT and help extend knowledge of advanced laser therapy.

  14. Antimicrobial photodynamic therapy in a mouse model of Acinetobacter baumannii burn infection

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    Dai, Tianhong; Tegos, George P.; Lu, Zongshun; Zhiyentayev, Timur; Huang, Liyi; Franklin, Michael J.; Baer, David G.; Hamblin, Michael R.

    2009-06-01

    Multi-drug resistant Acinetobacter baumanii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment using traditional antibiotics can be extremely difficult and new antimicrobial approaches are being investigated. One of these antimicrobial alternatives could be the combination of non-toxic photosensitizers (PS) and visible light known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by covalent conjugation chlorin(e6) to polyethylenimine followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-second burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted on average 22 days characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after applying bacteria gave over three logs of loss of bacterial luminescence in a light exposure dependent manner, while PDT carried out on day 1 and day 2 gave approximately a 1.7-log reduction. Application of PS dissolved in 10% or 20% DMSO without light gave only modest reduction in bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multi-drug resistant localized A. baumannii infections.

  15. Evaluation of the effect of photodynamic antimicrobial therapy in dentin caries: a pilot in vivo study

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    Borges, F. M. C.; de-Melo, M. A. S.; Lima, J. M. P.; Zanin, I. C. J.; Rodrigues, L. K. A.; Nobre-dos-Santos, M.

    2010-02-01

    In vitro and in situ studies have demonstrated that the photodynamic antimicrobial therapy (PACT) is effective in reducing Streptococcus mutans population in artificially carious dentin. This pilot in vivo study evaluated the antimicrobial effect of PACT using toluidine blue O (TBO) and a light-emitting diode (LED) in carious dentin lesions. Five healthy adult volunteers (19-36 yr), with at least 4 active carious cavities each, participated in this study. Teeth of each volunteer were randomly divided into four groups: (1) without TBO and without light (Control); (2) with TBO alone (TBO); (3) with LED at 94/J cm2 alone (LED); and (4) with TBO plus LED at 94 J/cm2 (PACT). Each cavity was divided into two halves. The baseline carious dentin sample was collected from half of each cavity. Following, the treatments were performed using a random distribution of tooth into treatments. Then, the second collection of carious dentin samples was performed. Before and after treatments, dentin samples were analyzed with regard to the counts of total viable microorganisms, total streptococci, mutans streptococci, and lactobacilli. The data were statistically analyzed by Kruskal-Wallis and Student-Newman-Keuls tests (α=5%). Log reductions ranged from -0.12 to 2.68 and significant reductions were observed for PACT (group 4) when compared to the other groups (1, 2, and 3) for total streptococci and mutans streptococci. Concluding, PACT was effective in killing oral microorganisms present in in vivo carious dentin lesions and may be a promising technique for eliminating bacteria from dentin before restoration.

  16. Antimicrobial photodynamic therapy for the treatment of teeth with apical periodontitis: a histopathological evaluation.

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    Silva, Lea Assed Bezerra; Novaes, Arthur B; de Oliveira, Rafael R; Nelson-Filho, Paulo; Santamaria, Milton; Silva, Raquel Assed Bezerra

    2012-03-01

    This study evaluated the in vivo response of apical and periapical tissues of dogs' teeth with apical periodontitis after one-session endodontic treatment with and without antimicrobial photodynamic therapy (aPDT). Sixty root canals with experimentally induced apical periodontitis were instrumented and assigned to 4 groups receiving aPDT and root canal filling (RCF) or not: group aPDT+/RCF+ (n = 20): aPDT (photosensitizer phenothiazine chloride at 10 mg/mL for 3 minutes and diode laser [λ = 660 nm, 60 mW/cm(2)] for 1 minute) and RCF in the same session; group aPDT+/RCF- (n = 10); group aPDT-/RCF+ (n = 20), and group aPDT-/RCF- (n = 10). Teeth were restored, and the animals were killed after 90 days. Sections from the maxillas and mandibles were stained with hematoxylin-eosin and Mallory trichrome and examined under light microscopy. Descriptive (ie, newly formed apical mineralized tissue, periapical inflammatory infiltrate, apical periodontal ligament thickness, and mineralized tissue resorption) and quantitative (ie, periapical lesion size and number of inflammatory cells) microscopic analysis was performed. Quantitative data were analyzed by the Kruskal-Wallis and Dunn tests (α = .05). In the aPDT-treated groups, the periapical region was moderately/severely enlarged with no inflammatory cells, moderate neoangiogenesis and fibrogenesis, and the smallest periapical lesions. Although apical closure by mineralized tissue deposition was not achieved, the absence of inflammatory cells, moderate neoangiogenesis, and fibrogenesis in the periapical region in the groups treated with aPDT indicate that this can be a promising adjunct therapy to cleaning and shaping procedures in teeth with apical periodontitis undergoing one-session endodontic treatment. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  17. Antimicrobial photodynamic therapy as an adjunct for treatment of deep carious lesions-A systematic review.

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    Cieplik, Fabian; Buchalla, Wolfgang; Hellwig, Elmar; Al-Ahmad, Ali; Hiller, Karl-Anton; Maisch, Tim; Karygianni, Lamprini

    2017-06-01

    For deep carious lesions, a more conservative treatment modality ("selective caries removal") has been proposed, where only the heavily contaminated dentine is removed. In this regard, effective adjuncts for cavity disinfection such as the antimicrobial photodynamic therapy (aPDT) can be valuable clinically prior to definitive restoration. Therefore, the aim of this study was to systematically assess clinical studies on the effectiveness of aPDT as a supplementary tool in the treatment of deep caries lesions. Searches were performed in four databases (PubMed, EMBASE, ISI Web of Science, ClinicalTrials.gov) from 1st January, 2011 until 21st June, 2016 for search terms relevant to the observed parameters, pathological condition, intervention and anatomic entity. The pooled information was evaluated according to PRISMA guidelines. At first, 1651 articles were recovered, of which 1249 full-text articles were evaluated, 270 articles thereof were reviewed for eligibility and finally 6 articles met all inclusion criteria. The aPDT protocols involved Methylene Blue, Toluidine Blue and aluminium-chloride-phthalocyanine as photosensitizers and diode lasers, light-emitting diodes and halogen light-sources. The data from five reports, utilizing both culture-dependent and -independent methods, disclosed significant reduction of cariogenic bacterial load after mechanical caries removal with adjunct aPDT. As these studies exhibit some methodological limitations, e.g. lack of positive controls, this systematic review can support the application of aPDT to a limited extent only in terms of reducing the microbial load in deep carious lesions before restorative treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Efficacy of antimicrobial photodynamic therapy as an adjuvant in periodontal treatment in Down syndrome patients.

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    Martins, Fabiana; Simões, Alyne; Oliveira, Marcio; Luiz, Ana Claudia; Gallottini, Marina; Pannuti, Claudio

    2016-12-01

    Down syndrome (DS) has characteristics that include mental retardation, a characteristic phenotype, congenital heart defects, immune disorders, and increased risk of periodontal disease (PD). Antimicrobial photodynamic therapy (aPDT) is the combined use of photosensitizers associated with low-level laser (LLL) and oxygen, leading to singlet oxygen formation, which contributes to the antibacterial activity of the phagocytes, killing bacteria. The objective of this study was to evaluate the efficacy of aPDT as an adjuvant to conventional periodontal treatment of PD in DS patients. A double-blinded, controlled, randomized, split-mouth study was conducted. A total of 13 DS subjects who were 18 years or older and who presented at least one tooth in each quadrant of the mouth with probing pocket depth (PPD) equal to or greater than 5 mm were included. The patients were evaluated at three different times: at the baseline, PPD were obtained. After 1 week, conventional scaling and root planing (SRP) was performed, and two randomly selected quadrants also received aPDT. One month after SRP, all the patients were reevaluated. Periodontal conditions were improved among all the participants. The PDT-with-SRP group presented a nonsignificant reduction in PPD (mean = 1.27 mm, median = 1.17 mm) relative to that of the SRP group (mean = 1.00 mm, median = 0.95 mm). Changes over time were compared using the Wilcoxon test. A significant reduction in median PPD was observed in both groups (p = 0.001). Both types of periodontal treatment, with and without PDT, were similarly effective and were associated with good clinical response.

  19. Antimicrobial photodynamic therapy for infectious stomatitis in snakes: Clinical views and microbiological findings.

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    Grego, Kathleen Fernandes; Carvalho, Marcelo Pires Nogueira de; Cunha, Marcos Paulo Vieira; Knöbl, Terezinha; Pogliani, Fabio Celidonio; Catão-Dias, José Luiz; Sant'Anna, Sávio Stefanini; Ribeiro, Martha Simões; Sellera, Fábio Parra

    2017-12-01

    Antimicrobial photodynamic therapy (APDT) has been broadly investigated as an alternative to treat localized infections, without leading to the selection of resistant microorganisms. Infectious stomatitis is a multifactorial disease frequently reported in captive snakes characterized by infection of the oral mucosa and surrounding tissues. In this study, we investigated methylene blue (MB)-mediated APDT to treat infectious stomatitis in snakes and verified the resistance phenotype and genotype before and after APDT. Three Boid snakes presented petechiae, edema and caseous material in their oral cavities. MB (0.01%) was applied on the lesions and after 5min they were irradiated using a red laser (λ=660nm), fluence of 280J/cm 2 , 8J and 80s per point, 100mW, spot size 0.028cm 2 and fluence rate of 3.5W/cm 2 . APDT was repeated once a week during 3 months. Samples of the lesions were collected to identify bacteria and antibiotic resistance profiles. To analyze the clonality of bacterial isolates before and after APDT, isolates were subjected to ERIC PCR analysis. Snakes presented clinical improvement such as reduction of inflammatory signs and caseous material. Pseudomonas aeruginosa and Escherichia coli were present in all snakes; Klebsiella pneumoniae and Morganella morganii were also identified in some animals. We also observed that the oral microbiota was completely replaced following APDT. However, K. pneumoniae isolates before and after APDT were a single clone with 100% of genetic similarity that lost resistance phenotype for seven antibiotics of four classes. These results show that APDT can be used to treat infectious stomatitis in snakes. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Photodynamic Therapy for Cancer

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    ... et al. Photodynamic therapy. Journal of the National Cancer Institute 1998; 90(12):889–905. [PubMed Abstract] Gudgin Dickson EF, Goyan RL, Pottier RH. New directions in photodynamic therapy. Cellular and Molecular Biology 2002; 48(8):939–954. [PubMed Abstract] Capella ...

  1. Photodynamic therapy in endodontics: a literature review.

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    Trindade, Alessandra Cesar; De Figueiredo, José Antônio Poli; Steier, Liviu; Weber, João Batista Blessmann

    2015-03-01

    Recently, several in vitro and in vivo studies demonstrated promising results about the use of photodynamic therapy during root canal system disinfection. However, there is no consensus on a standard protocol for its incorporation during root canal treatment. The purpose of this study was to summarize the results of research on photodynamic therapy in endodontics published in peer-reviewed journals. A review of pertinent literature was conducted using the PubMed database, and data obtained were categorized into sections in terms of relevant topics. Studies conducted in recent years highlighted the antimicrobial potential of photodynamic therapy in endodontics. However, most of these studies were not able to confirm a significant improvement in root canal disinfection for photodynamic therapy as a substitute for current disinfection methods. Its indication as an excellent adjunct to conventional endodontic therapy is well documented, however. Data suggest the need for protocol adjustments or new photosensitizer formulations to enhance photodynamic therapy predictability in endodontics.

  2. Photodynamic Therapy (PDT)

    Indian Academy of Sciences (India)

    Photodynamic Therapy (PDT) is a newly emerging modal- ... Porphyrins are a ubiquitous class of naturally occurring heterocyclic ..... mechanism leading to tumor necrosis. ... The vascular endothelium may be the main target of tumor.

  3. Antimicrobial photodynamic therapy with two photosensitizers on two oral streptococci: an in vitro study

    Science.gov (United States)

    Vahabi, S.; Fekrazad, R.; Ayremlou, S.; Taheri, S.; Lizarelli, R. F. Z.; Kalhori, K. A. M.

    2011-12-01

    Periodontal diseases are caused by infection of tissues supporting the teeth due to complex aggregate of bacteria known as biofilm and firstly colonized by streptococci. The aim of this in vitro study was to evaluate the effect of Radachlorin® and Toluidine Blue O (TBO)-mediated photodynamic therapy (PDT) on the viability of two oral streptococci. Bacterial suspensions of Streptococcus mutans and Streptococcus sanguis were subjected to either TBO or Radachlorin®, Then exposed to two different diode laser light at energy densities of 3, 6 J/cm2 at 633 nm and 6, 12 J/cm2 at 662 nm, respectively. The control groups were subjected to laser light alone, photosensitizer alone or received neither photosensitizer nor light exposure. The suspensions were then spread over specific agar mediums and viable microorganisms were counted after overnight incubation aerobically at 37°C, 5% CO2 and then reported as colony forming unit. The results indicated that photosensitization by the energy density of 6 J/cm2 with Radachlorin® and both 3 and 6 J/cm2 with TBO caused significant reduction in bacterial colony formation ( p < 0.05). Radachlorin® and TBO-mediated photodynamic therapy seem to show excellent potential in significantly killing of two oral streptococci in vitro.

  4. Oligolysine-conjugated zinc(II) phthalocyanines as efficient photosensitizers for antimicrobial photodynamic therapy.

    Science.gov (United States)

    Ke, Mei-Rong; Eastel, Jennifer Mary; Ngai, Karry L K; Cheung, Yuk-Yam; Chan, Paul K S; Hui, Mamie; Ng, Dennis K P; Lo, Pui-Chi

    2014-07-01

    A series of zinc(II) phthalocyanines conjugated with an oligolysine chain (n=2, 4, and 8) were synthesized and characterized by using various spectroscopic methods. As shown by using UV/Vis and fluorescence spectroscopic methods, these compounds were nonaggregated in N,N-dimethylformamide, and gave a weak fluorescence emission and high singlet oxygen quantum yield (Φ(Δ) =0.86-0.89) as a result of their di-α-substitution. They became slightly aggregated in water with 0.05 % Cremophor EL, but they could still generate singlet oxygen effectively. The antimicrobial photodynamic activities of these compounds were then examined against various bacterial strains, including the Gram-positive methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC BAA-43, and the Gram-negative Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853. Generally, the dyes were much more potent toward the Gram-positive bacteria. Only 15 to 90 nM of these photosensitizers was required to induce a 4 log reduction in the cell viability of the strains. For Escherichia coli, the photocytotoxicity increased with the length of the oligolysine chain. The octalysine derivative showed the highest potency with a 4 log reduction concentration of 0.8 μM. Pseudomonas aeruginosa was most resistant to the photodynamic treatment. The potency of the tetralysine derivative toward a series of clinical strains of Staphylococcus aureus was also examined and found to be comparable with that toward the nonclinical counterparts. Moreover, the efficacy of these compounds in photodynamic inactivation of viruses was also examined. They were highly photocytotoxic against the enveloped viruses influenza A virus (H1N1) and herpes simplex virus type 1 (HSV1), but exhibited no significant cytotoxicity against the nonenveloped viruses adenovirus type 3 (Ad3) or coxsackievirus (Cox B1). The octalysine derivative also showed the highest potency with

  5. Medication-Related Osteonecrosis of Jaws: A Low-Level Laser Therapy and Antimicrobial Photodynamic Therapy Case Approach

    Directory of Open Access Journals (Sweden)

    Mariana Comparotto Minamisako

    2016-01-01

    Full Text Available Medication-related osteonecrosis of the jaws (MRONJ can be considered an inability of the alveolar bone to respond to an injury, which frequently leads to severe local and systemic complications. Once the problem is installed, dentist must use all therapeutic approaches recommended. This manuscript reports a successful management of MRONJ handled with antibiotics, conservative debridement, low-level laser therapy (LLLT, and photodynamic therapy (PDT up to 12 months. As healing of MRONJ may be very slow, combined therapeutic approaches are required. Besides the recommended conventional treatment protocol, LLLT and PDT are important tools to contribute to healing and improvement of patient’s quality of life.

  6. The in vitro effect of Antimicrobial Photodynamic Therapy on dental microcosm biofilms from partially erupted permanent molars: A pilot study.

    Science.gov (United States)

    de Oliveira, Fabiana Sodré; Cruvinel, Thiago; Cusicanqui Méndez, Daniela Alejandra; Dionísio, Evandro José; Rios, Daniela; Machado, Maria Aparecida Andrade Moreira

    2018-03-01

    Antimicrobial Photodynamic Therapy (aPDT) could enhance the prevention of dental caries lesions in pits and fissures of partially erupted molars, by killing microorganisms from complex dental biofilms. This pilot study aimed to evaluate the effect of Antimicrobial Photodynamic Therapy (aPDT) on the viability of specific microorganism groups of dental microcosm biofilms from occlusal surfaces of first permanent molars in eruption. Dental microcosm biofilms grown on bovine enamel blocks, from dental plaque collected on occlusal surfaces of a partially erupted lower right first permanent molar, with McBain medium plus 1% sucrose in anaerobic condition at 37 °C for 72 h. The experiments were performed in eight groups: L-P- = no treatment (control), L18.75P- = 18.75 J/cm 2 LED, L37.5P- = 37.5 J/cm 2 LED, L75P- = 75 J/cm 2 LED, L-P+ = 200 mM TBO, L18.75P+ = 200 mM TBO + 18.75 J/cm 2 LED, L37.5P+ = 200 mM TBO + 37.5 J/cm 2 LED, and L75P+ = 200 mM TBO + 75 J/cm 2 LED. The counts of total microorganisms, total streptococci and mutans streptococci were determined on selective media agar plates by colony-forming units per mL. The log-transformed counts were analyzed by Kruskal-Wallis and post-hoc Dunn's test (P < 0.05). The counts of all microorganisms treated in the group L75P+ were statistically lower than those treated in L-P-. The aPDT promoted a significant reduction of microorganisms, with a trend of dose-dependent effect. TBO-mediated aPDT was effective in reducing the viability of specific microbial groups in dental microcosm biofilms originated from occlusal of permanent molars in eruption. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Antimicrobial photodynamic therapy-a promising treatment for prosthetic joint infections.

    Science.gov (United States)

    Briggs, Timothy; Blunn, Gordon; Hislop, Simon; Ramalhete, Rita; Bagley, Caroline; McKenna, David; Coathup, Melanie

    2018-04-01

    Periprosthetic joint infection (PJI) is associated with high patient morbidity and a large financial cost. This study investigated Photodynamic Therapy (PDT) as a means of eradicating bacteria that cause PJI, using a laser with a 665-nm wavelength and methylene blue (MB) as the photosensitizer. The effectiveness of MB concentration on the growth inhibition of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter baumannii was investigated. The effect of laser dose was also investigated and the optimized PDT method was used to investigate its bactericidal effect on species within planktonic culture and following the formation of a biofilm on polished titanium and hydroxyapatite coated titanium discs. Results showed that Staphylococci were eradicated at the lowest concentration of 0.1 mM methylene blue (MB). With P. aeruginosa and A. baumannii, increasing the MB concentration improved the bactericidal effect. When the laser dose was increased, results showed that the higher the power of the laser the more bacteria were eradicated with a laser power ≥ 35 J/cm 2 and an irradiance of 35 mW/cm 2 , eradicating all S. epidermidis. The optimized PDT method had a significant bactericidal effect against planktonic MRSA and S. epidermidis compared to MB alone, laser alone, or control (no treatment). When biofilms were formed, PDT treatment had a significantly higher bactericidal effect than MB alone and laser alone for all species of bacteria investigated on the polished disc surfaces. P. aeruginosa grown in a biofilm was shown to be less sensitive to PDT when compared to Staphylococci, and a HA-coated surface reduced the effectiveness of PDT. This study demonstrated that PDT is effective for killing bacteria that cause PJI.

  8. Effect of the antimicrobial photodynamic therapy on microorganism reduction in deep caries lesions: a systematic review and meta-analysis

    Science.gov (United States)

    Ornellas, Pâmela Oliveira; Antunes, Leonardo Santos; Fontes, Karla Bianca Fernandes da Costa; Póvoa, Helvécio Cardoso Corrêa; Küchler, Erika Calvano; Iorio, Natalia Lopes Pontes; Antunes, Lívia Azeredo Alves

    2016-09-01

    This study aimed to perform a systematic review to assess the effectiveness of antimicrobial photodynamic therapy (aPDT) in the reduction of microorganisms in deep carious lesions. An electronic search was conducted in Pubmed, Web of Science, Scopus, Lilacs, and Cochrane Library, followed by a manual search. The MeSH terms, MeSH synonyms, related terms, and free terms were used in the search. As eligibility criteria, only clinical studies were included. Initially, 227 articles were identified in the electronic search, and 152 studies remained after analysis and exclusion of the duplicated studies; 6 remained after application of the eligibility criteria; and 3 additional studies were found in the manual search. After access to the full articles, three were excluded, leaving six for evaluation by the criteria of the Cochrane Collaboration's tool for assessing risk of bias. Of these, five had some risk of punctuated bias. All results from the selected studies showed a significant reduction of microorganisms in deep carious lesions for both primary and permanent teeth. The meta-analysis demonstrated a significant reduction in microorganism counts in all analyses (p<0.00001). Based on these findings, there is scientific evidence emphasizing the effectiveness of aPDT in reducing microorganisms in deep carious lesions.

  9. Effect of antimicrobial photodynamic therapy on the counts of salivary Streptococcus mutans in children with severe early childhood caries.

    Science.gov (United States)

    Fekrazad, Reza; Seraj, Bahman; Chiniforush, Nasim; Rokouei, Mehrak; Mousavi, Niloofar; Ghadimi, Sara

    2017-06-01

    Antimicrobial photodynamic therapy (aPDT) is a novel technique for reduction of pathogenic microorganisms in dentistry. The aim of this study was to evaluate the effects of aPDT on Streptococcus mutans reduction in children with severe early childhood caries. Twenty-two children with severe early childhood caries aged 3-6 years were treated with toluoidine blue O (TBO) for 1min and irradiated by a Light Emitting Diode (LED; FotoSan, CMS Dental, Denmark) with the exposure time of 150s. Saliva samples were collected at baseline, 1h and 7 days after treatment. S. mutans counts were determined using the Dentocult SM Strip mutans. The counts of S. mutans in saliva decreased significantly after 1h (Pmutans counts in saliva was not significant between the baseline and 7 days after treatment (P>0.05). aPDT seems to be efficient to reduce salivary S. mutans immediately after treatment in children with severe early childhood caries. However, further research is needed to evaluate different doses and frequency of irradiation in combination with restoring carious teeth to find more durable results. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Antimicrobial photodynamic therapy with photosensitizer in ethanol improves oxidative status and gingival collagen in a short-term in periodontitis.

    Science.gov (United States)

    Pillusky, Fernanda Maia; Barcelos, Raquel Cristine Silva; Vey, Luciana Taschetto; Barin, Luisa Machado; de Mello Palma, Victor; Maciel, Roberto Marinho; Kantorski, Karla Zanini; Bürger, Marilise Escobar; Danesi, Cristiane Cademartori

    2017-09-01

    This study evaluated the antimicrobial photodynamic therapy (aPDT) effects using the methylene blue (MB) in ethanol 20% on systemic oxidative status and collagen content from gingiva of rats with periodontitis. Rats were divided into five experimental groups: NC (negative control; no periodontitis); PC (positive control; periodontitis without any treatment); SRP (periodontitis and scaling and root planing), aPDT I (periodontitis and SRP+aPDT+MB solubilized in water), and aPDT II (periodontitis and SRP+aPDT+MB solubilized in ethanol 20%). After 7days of removal of the ligature, the periodontal treatments were performed. At 7/15/30days, gingival tissue was removed for morphometric analysis. The erythrocytes were used to evaluate systemic oxidative status. PC group showed higher lipoperoxidation levels at 7/15/30days. aPDT indicated a protective influence in erythrocytes at 15days observed by the elevation in levels of systemic antioxidant defense. aPDT II group was the only one that restored the total collagen area in 15days, and recovered the type I collagen area at the same time point. aPDT as an adjunct to the SRP can induce the systemic protective response against oxidative stress periodontitis-induced and recover the gingival collagen, thus promoting the healing periodontal, particularly when the MB is dissolved in ethanol 20%. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Reducing Vibrio load in Artemia nauplii using antimicrobial photodynamic therapy: a promising strategy to reduce antibiotic application in shrimp larviculture

    Science.gov (United States)

    Asok, Aparna; Arshad, Esha; Jasmin, C.; Somnath Pai, S.; Bright Singh, I. S.; Mohandas, A.; Anas, Abdulaziz

    2012-01-01

    Summary We propose antimicrobial photodynamic therapy (aPDT) as an alternative strategy to reduce the use of antibiotics in shrimp larviculture systems. The growth of a multiple antibiotic resistant Vibrio harveyi strain was effectively controlled by treating the cells with Rose Bengal and photosensitizing for 30 min using a halogen lamp. This resulted in the death of > 50% of the cells within the first 10 min of exposure and the 50% reduction in the cell wall integrity after 30 min could be attributed to the destruction of outer membrane protein of V. harveyi by reactive oxygen intermediates produced during the photosensitization. Further, mesocosm experiments with V. harveyi and Artemia nauplii demonstrated that in 30 min, the aPDT could kill 78.9% and 91.2% of heterotrophic bacterial and Vibrio population respectively. In conclusion, the study demonstrated that aPDT with its rapid action and as yet unreported resistance development possibilities could be a propitious strategy to reduce the use of antibiotics in shrimp larviculture systems and thereby, avoid their hazardous effects on human health and the ecosystem at large. PMID:21951316

  12. Treatment of periodontitis in smokers with multiple sessions of antimicrobial photodynamic therapy or systemic antibiotics: A randomized clinical trial.

    Science.gov (United States)

    Theodoro, Letícia Helena; Assem, Naida Zanini; Longo, Mariéllen; Alves, Márcio Luiz Ferro; Duque, Cristiane; Stipp, Rafael Nobrega; Vizoto, Natália Leal; Garcia, Valdir Gouveia

    2018-06-01

    The aim of this study was to evaluate the effects of non-surgical periodontal therapies on smokers with chronic periodontitis, involving multiple adjunctive applications of antimicrobial photodynamic therapy (aPDT), and systemic metronidazole (MTZ) with amoxicillin (AMX). All participants were treated with scaling and root planing (SRP). Seventeen patients received 400 mg of MTZ and 500 mg of AMX three times per day for 7 days (MTZ + AMX). Additionally, 17 patients received a placebo, and 17 patients were treated with three applications of aPDT (immediately, 48 h and 96 h after SRP). Clinical and microbiological examinations were performed at baseline and at 90 and 180 days post-therapy. Subgingival samples were analyzed using real-time polymerase chain reaction. After 180 days, the patients in groups MTZ + AMX and aPDT had significantly lower mean probing depths, more clinical attachment level gains and less bleeding on probing. At 180 days, in the moderate pocket there was a reduction in the levels of Porphyromonas gingivalis and Prevotella nigrescens in the MTZ + AMX group, while group aPDT showed a reduction in Prevotella nigrescens. Furthermore, at 180 days, in the deep pocket a reduction in Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens was observed in group MTZ + AMX, as well as a reduction in the levels of Prevotella intermedia and Prevotella nigrescens in group aPDT. In smokers with periodontitis, the MTZ + AMX and aPDT treatments significantly improved the effects of SRP. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. The antimicrobial effectiveness of photodynamic therapy used as an addition to the conventional endodontic re-treatment: a clinical study.

    Science.gov (United States)

    Jurič, Ivona Bago; Plečko, Vanda; Pandurić, Dragana Gabrić; Anić, Ivica

    2014-12-01

    The purpose of the study was to evaluate the efficacy of antimicrobial photodynamic therapy (aPDT) used as an adjunct to the endodontic re-treatment in the eradication of microorganisms from previously filled root canals. The study sample consisted of 21 randomly selected patients with root filled and infected root canal system with chronic apical periodontitis on incisors or canines, who have had previously endodontic treatment. Microbiological samples from the root canals were collected after accessing the canal, following the endodontic re-treatment and after the aPDT procedure. During instrumentation, the root canals were irrigated with 2.5% sodium hypochlorite (NaOCl), and the final irrigation protocol included 17% ethylenediaminetetraacetic acid followed by NaOCl. Root canals were filled with a phenothiazinium chloride and irradiated with a diode laser (λ=660 nm, 100 mW) for 1 min. Microbiological samples from the root canals were cultivated on selective plates, and the identification was done by micromorphology, macromorphology and different API strips as well as bacterial counts (colony forming units). Fourteen bacteria species were isolated from the root canals initially, with a mean value of 4.57 species per canal. Although endodontic re-treatment alone produced a significant reduction in the number of bacteria species (pendodontic treatment and aPDT was statistically more effective (proot canals of 11 teeth. The results indicated that the aPDT used as an adjunct to the conventional endodontic therapy achieved a significant further reduction of intracanal microbial load. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Photodynamic antimicrobial therapy in the treatment of denture stomatitis; Terapia fotodinamica antimicrobiana no tratamento da estomatite protetica

    Energy Technology Data Exchange (ETDEWEB)

    Senna, Andre Machado de

    2012-07-01

    Denture stomatitis (DS), also called chronic atrophic candidiasis, is the most common oral fungal infection in denture wearers. It has a multifactorial etiology, but the presence of Candida spp. biofilm on the denture is considered the most important factor for the establishment of the DS. This study aimed to evaluate the treatment of DS through the use of photodynamic antimicrobial therapy (PAT), mediated by methylene blue. For this purpose, preclinical studies and clinical trials were performed. Simulators prototypes dentures were made of methyl methacrylate polymer to serve as a basis for biofilm growth of the following species of Candida: C. albicans, C. glabrata, C. dubliniensis, C. krusei, C. tropicalis, C. parapsilosis and C. guilliermondii. Methylene blue solution at a concentration of 450 {mu}g/mL was used as a photosensitizer. The prototypes and biofilms were irradiated with a laser of wavelength of 660 nm, potency of 100 mW, for 80 seconds. For the clinical study, subjects were divided into two groups. The first group received conventional treatment based on the use of antifungal Miconazole. The second group received the treatment by PAT. The preclinical results showed that all species of the genus Candida were susceptible to PAT, with a reduction in colonies that ranged from 2.48 to 3.93 log{sub 10}. Clinical outcomes were evaluated for the reduction of colonies of Candida spp. located in the mucosa and in the prosthesis and relative to the improvement of the clinical aspect of the affected mucosa. Both the conventional therapy and PAT were effective in treating DS. There was no significant statistical difference between PAT and conventional treatment for any of the factors evaluated. Thus, it was concluded that PAT is effective in the treatment of denture stomatitis. (author)

  15. One-session root canal treatment with antimicrobial photodynamic therapy (aPDT): an in vivo study.

    Science.gov (United States)

    Borsatto, M C; Correa-Afonso, A M; Lucisano, M P; Bezerra da Silva, R A; Paula-Silva, F W G; Nelson-Filho, P; Bezerra da Silva, L A

    2016-06-01

    To evaluate the response of the apical and periapical tissues of dog teeth with apical periodontitis after one-session root canal treatment with and without antimicrobial photodynamic therapy (aPDT) compared with the use of an intracanal dressing. Sixty root canals with an induced periapical lesion were instrumented and assigned to three groups: I, two-session root canal treatment using antibacterial dressing with calcium hydroxide-based paste; II, one-session root canal treatment using aPDT; and III, one-session root canal treatment in which the root canals were filled immediately after biomechanical preparation. The animals were euthanized after a 90-day experimental period. The maxillas and mandibles with teeth were submitted to histotechnical processing and haematoxylin-eosin staining. Descriptive microscopic analysis of the apical and periapical region characteristics was performed, as well as morphometric assessment of the periapical lesion areas in fluorescence microscopy. Quantitative data were analysed statistically by the nonparametric Kruskal-Wallis test and Dunn's post-test (α = 0.05). Group I was characterized by progressive repair, with the presence of fibres, cells and blood vessels. Group II had periodontal ligaments with the presence of collagen fibres and residual inflammatory cells. Group III had a dense inflammatory infiltrate with extensive oedematous areas and fibrillar dissociation, suggesting a persistent inflammatory and resorptive condition. Regarding periapical lesion size, group I had significantly smaller lesions (P session root canal treatment using a calcium hydroxide-based dressing was associated with significantly smaller periapical lesions at 90 days and characterized by progressive repair. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  16. Evaluation of the efficacy of photodynamic antimicrobial therapy using a phenothiazine compound and LED (red-orange) on the interface: macrophage vs S. aureus

    Science.gov (United States)

    Sampaio, Fernando José P.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Pires-Santos, Gustavo M.; Gesteira, Maria F. M.; Pinheiro, Antônio L. B.

    2015-03-01

    Antimicrobial Photodynamic therapy is a technique in which microorganisms are exposed to a photosensitizing drug and then irradiated with low-intensity visible light of the appropriate wavelength. The resulting photochemical reaction generates cytotoxic reactive oxygen species, such as singlet oxygen and free radicals, which are able to exert bactericidal effect. Much is already known about the photodynamic inactivation of microorganisms: both antibiotic-sensitive and - resistant strains can be successfully photo inactivated, and there is the additional advantage that repeated photosensitization of bacterial cells does not induce a selection of resistant strains. Recently, a series of studies have shown that it is possible to kill bacteria with a light source after the microorganisms have been sensitized with low concentration of dye, such as phenothiazines. The aim of this study was to evaluate the phagocytic function of macrophages J774 against S. aureus in the presence and absence of AmPDT with phenothiazine compound (12.5 μg/mL) and red-orange LED. Experimental groups: Control Group (L-F-), Phenothiazine group (L-F+) LED group (L+F-), Photodynamic therapy group (L+F+). The tests presented in this study were carried out in triplicate. This study demonstrated that AmPDT is able to increase about twice the phagocytic ability of macrophages; however, the bactericidal capacity of these cells did not show a substantial improvement, probably because the oxidative burst was less intense.

  17. PHOTODYNAMIC THERAPY OF CONDYLOMATA ACUMINATE

    Directory of Open Access Journals (Sweden)

    V. N. Galkin

    2016-01-01

    Full Text Available Reliably established a causal role of human papillomavirus in the formation of condylomata acuminate. In 10% of people with the human papilloma virus develops condylomata acuminate, which can be transformed into malignant tumors. The most common treatment of condylomata acuminate is a conservative treatment, namely, the local chemical or physical destruction of the lesions and immunotherapy. With the ineffectiveness of conservative treatment resort to surgical excision. At the same time the traditional methods of treatment condylomata acuminate associated with high rates of recurrence. Moreover, these treatments are often associated with significant risk of bleeding, ulceration and scarring. The emergence of new methods of diagnosis and treatment of condylomata acuminate – fluorescence diagnosis and photodynamic therapy has opened up new opportunities to improve the treatment of this pathology. Topical administration of photosensitizers during photodynamic therapy is more convenient and less phototoxic and broaden the range of clinical applications of this technology in the medical dermatology. An increasing amount of evidence that photodynamic therapy with topical application of the photosensitizer is highly effective in the treatment of a variety of benign skin diseases, including condylomata acuminataca, for which traditional methods are ineffective treatment. However, many parameters of photodynamic therapy of this disease has not yet been optimized. It is necessary to conduct large-scale clinical studies on the effectiveness of photodynamic therapy of condylomata acuminatain order to standardize the treatment parameters.

  18. Photodynamic therapy in clinical practice

    Directory of Open Access Journals (Sweden)

    E. V. Filonenko

    2016-01-01

    Full Text Available The review is on opportunities and possibilities of application of photodynamic therapy in clinical practice. The advantages of this method are the targeting of effect on tumor foci and high efficiency along with low systemic toxicity. The results of the set of recent Russian and foreign clinical trials are represented in the review. The method is successfully used in clinical practice with both radical (for early vulvar, cervical cancer and pre-cancer, central early lung cancer, esophageal and gastric cancer, bladder cancer and other types of malignant tumors, and palliative care (including tumor pleuritis, gastrointestinal tumors and others. Photodynamic therapy delivers results which are not available for other methods of cancer therapy. Thus, photodynamic therapy allows to avoid gross scars (that is very important, for example, in gynecology for treatment of patients of reproductive age with cervical and vulvar cancer, delivers good cosmetic effect for skin tumors, allows minimal trauma for intact tissue surrounding tumor. Photodynamic therapy is also used in other fields of medicine, such as otorhinolaryngology, dermatology, ophthalmology, orthopaedics, for treatment of papilloma virus infection and purulent wounds as antibacterial therapy.

  19. Photodynamic Therapy (PDT)

    Indian Academy of Sciences (India)

    transfer to oxygen, the cytotoxic singlet oxygen (102) resulting ... reactions. Thus, the available wavelengths for photodynamic sensitizers are 600-850 nm (red light). .... a: squamous cell carcinoma of a 78-year-old man. b: 1 week after PDT, .... relying on the heme's PDT action and (ii) noncancerous objects (i.e., healthy ...

  20. Photodynamic Therapy (PDT) - Basic Principles

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 4. Photodynamic Therapy (PDT) - Basic Principles. Bhaskar G Maiya. Series Article Volume 5 Issue 4 April 2000 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/005/04/0006-0018 ...

  1. Is Antimicrobial Photodynamic Therapy Effective as an Adjunct to Scaling and Root Planing in Patients with Chronic Periodontitis? A Systematic Review

    Directory of Open Access Journals (Sweden)

    Betsy Joseph

    2017-11-01

    Full Text Available The aim of this systematic review was to investigate whether antimicrobial photodynamic therapy (aPDT as either a primary mode of treatment or an adjunct to non-surgical treatment was more effective than scaling and root planing (SRP alone in treating chronic periodontitis in terms of clinical attachment level (CAL gain and probing depth (PD reduction. The focused question was developed using the Patient, Intervention, Comparison, and Outcome (PICO format, and two authors independently searched the Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies from January 2008 to December 2016. Twenty studies included in this systematic review were randomized clinical trials (RCTs or quasi-RCTs of aPDT compared to placebo, no intervention, or non-surgical treatment in an adult population. Basic study characteristics, photosensitizing agents and wavelengths used in aPDT, frequency of aPDT application, effect of aPDT on clinical parameters, antimicrobial effect of aPDT in chronic periodontitis, effect of immunological parameters following aPDT and patient-based outcome measures were collected from the studies. Although there was a wide range of heterogeneity in the included studied, they all indicated that aPDT has the potential to be an effective adjunct in the treatment of chronic periodontitis. Long-term, multicenter studies with larger sample sizes are needed before aPDT can be recommended as an effective treatment modality.

  2. Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes

    OpenAIRE

    Hamblin, Michael R

    2016-01-01

    Photodynamic therapy (PDT) uses photosensitizers (non-toxic dyes) that are activated by absorption of visible light to form reactive oxygen species (including singlet oxygen) that can oxidize biomolecules and destroy cells. Antimicrobial photodynamic inactivation (aPDI) can treat localized infections. aPDI neither causes any resistance to develop in microbes, nor is affected by existing drug resistance status. We discuss some recent developments in aPDI. New photosensitizers including polycat...

  3. The effect of antimicrobial photodynamic therapy on the expression of novel methicillin resistance markers determined using cDNA-AFLP approach in Staphylococcus aureus.

    Science.gov (United States)

    Hoorijani, Mohammad Neshvan; Rostami, Hosein; Pourhajibagher, Maryam; Chiniforush, Nasim; Heidari, Mansour; Pourakbari, Babak; Kazemian, Hossein; Davari, Kambiz; Amini, Vahid; Raoofian, Reza; Bahador, Abbas

    2017-09-01

    Widespread methicillin resistant Staphylococcus aureus (MRSA) and absence of effective antimicrobial agents has led to limited therapeutic options for treating MRSA infection. We aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) on the expression of novel identified methicillin resistance markers (NIMRMs) in S. aureus using complementary DNA-Amplified Fragment Length Polymorphism (cDNA-AFLP) approaches to address the therapeutic alternatives for MRSA infections. We used cDNA-AFLP to compare MRSA and methicillin susceptible S. aureus (MSSA) for identification of target genes implicated in methicillin resistance. To determine the sub-lethal aPDT (sPDT), MRSA and MSSA clinical isolates photosensitized with toluidine blue O (TBO), and then were irradiated with diode laser. After sPDT, the colony forming units/mL was quantified. Antimicrobial susceptibility against methicillin was assessed for cell-surviving aPDT. Effects of sPDT on the expression of NIMRMs were evaluated by real-time quantitative reverse transcription PCR. According to our results, serine hydrolase family protein (Shfp) encoding gene and a gene encoding a conserved hypothetical protein (Chp) were implicated in methicillin resistance in MRSA. sPDT reduced the minimum inhibitory concentrations of methicillin by 3-fold in MRSA. sPDT could lead to about 10- and 6.2- fold suppression of expression of the Chp and Shfp encoding genes, respectively. sPDT would lead to reduction in resistance to methicillin of MRSA in surviving cells by suppressing the expression of the Shfp and Chp encoding genes associated with methicillin resistance. This may have potential implications of aPDT for the treatment of MRSA infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Photodynamic therapy for basal cell carcinoma.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  5. Histopathological, Microbiological, and Radiographic Analysis of Antimicrobial Photodynamic Therapy for the Treatment of Teeth with Apical Periodontitis: A Study in Rats' Molars.

    Science.gov (United States)

    Trindade, Alessandra Cesar; de Figueiredo, José Antônio Poli; de Oliveira, Sílvia Dias; Barth Junior, Valdir Cristóvão; Gallo, Stephanie Wagner; Follmann, Carina; Wolle, Carlos Frederico Brilhante; Steier, Liviu; Morgental, Renata Dornelles; Weber, João Batista Blessmann

    2017-07-01

    The aim of this study was to evaluate in vivo, by histological and radiographic analysis, the response of apical tissues of rats' teeth with experimentally induced apical periodontitis, after one- and two-session endodontic treatment with and without photodynamic therapy (PDT). A microbiological analysis was also performed to verify bacterial reduction after each treatment. Studies carried out in recent years highlighted the antibacterial potential of PDT when associated with conventional endodontic therapy in vitro. Although the antimicrobial effect of PDT is well-established, tissue response to PDT in teeth with apical periodontitis lacks studies. Thirty-two rats' root canals were assigned to four groups: one session/PDT-[chemomechanical preparation (CMP)+root canal filling (RCF)]; two sessions/PDT- [CMP+calcium hydroxide (CH) for 14 days+RCF]; one session/PDT+ [CMP+PDT+RCF], and two sessions/PDT+ [CMP+PDT+CH for 14 days+RCF]. For microbiological evaluation, samples were collected before and after proposed treatments. For radiographic and histological analysis, the animals were euthanized after 28 days and the mandibles surgically removed. PDT associated with conventional endodontic therapy was able to promote significant bacterial reduction in root canals with induced apical periodontitis, but this reduction was not significantly different to conventional endodontic therapy alone. Although radiographic evaluation showed no significant differences, histological analysis showed lower scores for neutrophils/eosinophils in PDT-treated groups and macrophages/giant cells in CH groups. The use of low-level laser as light source did not promote major improvement on radiographic and histological repair, but since the number of inflammatory cells slightly decreased, it may optimize repair by modulating inflammatory process. PDT may be indicated as an adjunct to conventional endodontic therapy for teeth with apical periodontitis, in association with an interappointment

  6. Antimicrobial photodynamic therapy combined with periodontal treatment for metabolic control in patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Evangelista, Erika Elisabeth; França, Cristiane Miranda; Veni, Priscila; de Oliveira Silva, Tamires; Gonçalves, Rafael Moredo; de Carvalho, Verônica Franco; Deana, Alessandro Melo; Fernandes, Kristianne P S; Mesquita-Ferrari, Raquel A; Camacho, Cleber P; Bussadori, Sandra Kalil; Alvarenga, Letícia Heineck; Prates, Renato Araujo

    2015-05-27

    The relationship between diabetes mellitus (DM) and periodontal disease is bidirectional. DM is a predisposing and modifying factor of periodontitis, which, in turn, worsens glycemic control and increases proteins found in the acute phase of inflammation, such as C-reactive protein. The gold standard for the treatment of periodontal disease is oral hygiene orientation, scaling and planing. Moreover, systemic antibiotic therapy may be employed in some cases. In an effort to minimize the prescription of antibiotics, photodynamic therapy (PDT) has been studied as an antimicrobial technique and has demonstrated promising results. The aim of the proposed study is to determine whether PDT as a complement to periodontal therapy (PT) is helpful in the metabolic control of individuals with type 2 diabetes and the reduction of acute-phase inflammatory markers. The patients will be randomized using a proper software program into two groups: 1) PT + placebo PDT or 2) PT + active PDT. All patients will first be examined by a specialist, followed by PT performed by two other healthcare professionals. At the end of each session, PDT (active or placebo) will be administered by a fourth healthcare professional. The following will be the PDT parameters: diode laser (660 nm); power output = 110 mW; exposure time = 90 s per point (9 J/point); and energy density = 22 J/cm(2). The photosensitizer will be methylene blue (50 μg/mL). The patients will be re-evaluated 15, 30, 90 and 180 days after treatment. Serological examinations with complete blood count, fasting glucose, glycated hemoglobin and salivary examinations to screen for tumor necrosis factor alpha, interleukin 1, interleukin 6, ostelocalcin, and osteoprotegerin/RANKL will be performed at each evaluation. The data will be statistically evaluated using the most appropriate tests. The results of this study will determine the efficacy of photodynamic therapy as an adjuvant to periodontal treatment in diabetic patients. The

  7. Nanodrug applications in photodynamic therapy.

    LENUS (Irish Health Repository)

    Paszko, Edyta

    2011-03-01

    Photodynamic therapy (PDT) has developed over last century and is now becoming a more widely used medical tool having gained regulatory approval for the treatment of various diseases such as cancer and macular degeneration. It is a two-step technique in which the delivery of a photosensitizing drug is followed by the irradiation of light. Activated photosensitizers transfer energy to molecular oxygen which results in the generation of reactive oxygen species which in turn cause cells apoptosis or necrosis. Although this modality has significantly improved the quality of life and survival time for many cancer patients it still offers significant potential for further improvement. In addition to the development of new PDT drugs, the use of nanosized carriers for photosensitizers is a promising approach which might improve the efficiency of photodynamic activity and which can overcome many side effects associated with classic photodynamic therapy. This review aims at highlighting the different types of nanomedical approaches currently used in PDT and outlines future trends and limitations of nanodelivery of photosensitizers.

  8. Photodynamic therapy in dentistry: a literature review.

    Science.gov (United States)

    Gursoy, Hare; Ozcakir-Tomruk, Ceyda; Tanalp, Jale; Yilmaz, Selçuk

    2013-05-01

    The purpose of this review was to summarize recent developments regarding photodynamic therapy (PDT) in the field of dentistry. A review of pertinent literature was carried out in PubMED to determine the current position of PDT applications in dentistry. One hundred thirteen relevant articles were retrieved from PubMED by inserting the keywords "photodynamic therapy", "dentistry", "periodontology", "oral surgery", and "endodontics". It is anticipated that this overview will create a specific picture in the practitioner's mind regarding the current status and use of PDT. In spite of different results and suggestions brought about by different researchers, PDT can be considered as a promising and less invasive technique in dentistry. PDT seems to be an effective tool in the treatment of localized and superficial infections. Within the limitations of the present review, it can be concluded that although PDT cannot replace antimicrobial therapy at its current stage, it may be used as an adjunctive tool for facilitating the treatment of oral infections. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry.

  9. Photodynamic antimicrobial polymers for infection control.

    Directory of Open Access Journals (Sweden)

    Colin P McCoy

    Full Text Available Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene (HDPE using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA, and by up to 1.51 Log CFU/cm(2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.

  10. Photodynamic therapy of intraocular cancers

    International Nuclear Information System (INIS)

    Gravier, N.; Duvournau, Y.; Querec, M.A.; Pechereau, A.; Patrice, T.

    1992-01-01

    The most common intraocular tumors are choroidal malignant melanomas (70%) and retinoblastomas (13%). Each time that visual acuity is preserved, various conservative treatments are considered relative to the potential risk of metastatic disease during enucleation. In addition to standard techniques, photodynamic therapy is a potentially attractive new approach limited in its effects to the area of the treated tumor. The purpose of this preclinical study is to determine a reference dose-effect for single laser doses and to study effects of fractionation of the laser dose. (author). 9 refs., 1 tab

  11. Photodynamic therapy for cervical lesions

    Directory of Open Access Journals (Sweden)

    E. V. Grebenkina

    2014-01-01

    Full Text Available The experience of treatment for precancer and early cervical cancer by photodynamic therapy in 12 patients with primary diagnosis H-SIL (CIN II–III and cancer in situ is described. Chlo-rine photosensitizer Photolon was given intravenously at a dose of 0.75–1.15 mg/kg body weight. 2.5 h later the treatment with polyposition laser exposure (light dose – 150 J/cm2, light power density – 400–500 mW/cm2 was made. Thirty days later conization of the cervix with endocervical curettage assessing therapeutic response of cervical tumor tissue was per-formed. According to histological data complete response was in 4 patients, minute foci of CIN I were determined in 7 patients, 1 patient had foci of CIN II. 8 of 10 HPV-positive patients had complete eradication of HPV after treatment. There were no serious adverse events after light exposure. Marked therapeutic response, high anti-viral activity and good feasibility allow to consider photodynamic therapy as alternative organ-sparing treatment of early cancer and pre-cancer of cervix. 

  12. Fluorescent standards for photodynamic therapy

    Science.gov (United States)

    Belko, N.; Kavalenka, S.; Samtsov, M.

    2016-08-01

    Photodynamic therapy is an evolving technique for treatment of various oncological diseases. This method employs photosensitizers - species that lead to death of tumor cells after the photoactivation. For further development and novel applications of photodynamic therapy new photosensitizers are required. After synthesis of a new photosensitizer it is important to know its concentration in different biological tissues after its administration and distribution. The concentration is frequently measured by the extraction method, which has some disadvantages, e.g. it requires many biological test subjects that are euthanized during the measurement. We propose to measure the photosensitizer concentration in tissue by its fluorescence. For this purpose fluorescent standards were developed. The standards are robust and simple to produce; their fluorescence signal does not change with time. The fluorescence intensity of fluorescent standards seems to depend linearly on the dye concentration. A set of standards thus allow the calibration of a spectrometer. Finally, the photosensitizer concentration can be determined by the fluorescence intensity after comparing the corresponding spectrum with spectra of the set of fluorescent standards. A biological test subject is not euthanized during this kind of experiment. We hope this more humane technique can be used in future instead of the extraction method.

  13. Antimicrobial activity of photodynamic therapy in combination with colistin against a pan-drug resistant Acinetobacter baumannii isolated from burn patient.

    Science.gov (United States)

    Boluki, Ebrahim; Kazemian, Hossein; Peeridogaheh, Hadi; Alikhani, Mohammad Yousef; Shahabi, Sima; Beytollahi, Leili; Ghorbanzadeh, Roghayeh

    2017-06-01

    Nosocomially-acquired multi-, extensively-, and pandrug resistant (MDR, XDR, and PDR) strains of microorganisms such as Acinetobacter baumannii remain a serious cause of infection and septic mortality in burn patients. Treatment of patients with nosocomial burn wound infections is often complicated by drug-resistant strains of A. baumannii. Today, many researchers are focusing on the investigation of novel non-antibiotic strategies such as photodynamic therapy (PDT). We report a new PDT strategy that suppresses colistin resistance in PDR A. baumannii by interfering with the expression of a pmrA/pmrB two-component system. In the current study, A. baumannii with a PDR feature isolated from a burn patient was used as a test strain. PDT was carried out using toluidine blue O (TBO) and light-emitting diode (LED) as a photosensitizer and radiation source, respectively. The antimicrobial susceptibility profiles were assessed for cells surviving PDT. The effects of sub-lethal PDT (sPDT) on the expression of the pmrA/pmrB two-component signal transduction system were evaluated by real-time quantitative reverse transcription PCR. Results of drug susceptibly testing (DST) in LED and TBO groups separately showed that the bacteria were resistant to all tested antibiotics, while the DST result of the LED+TBO group showed highly declining bacterial growth when compared with the control group. Reduction in the expression of pmrA and pmrB was observed in the treated strains after sPDT. This represents the first conclusive example of a direct role for the PDT in breaking antibiotic resistance by directly modulating two-component system activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Is antimicrobial photodynamic therapy an effective treatment for chronic periodontitis in diabetes mellitus and cigarette smokers: a systematic review and meta-analysis.

    Science.gov (United States)

    Al-Hamoudi, Nawwaf

    2017-09-01

    To determine whether treatment with antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) improves clinical, microbiological and immunological outcomes in type 2 diabetes mellitus (T2DM) and cigarette smokers with chronic periodontitis (CP). Databases (MEDLINE, PubMed; Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register) were searched up to and including May 2017. The addressed PICO question was: "Does aPDT as an adjunct to SRP improves clinical, microbiological and immunological outcomes in T2DM and smokers with CP?" Six randomized clinical trials were included. All studies reporting clinical periodontal, microbiological, and immunological parameters showed that aPDT was effective in the treatment of CP in T2DM and smokers at follow up. When compared with SRP alone, none of the studies showed additional benefits of aPDT at follow up. Considering the effects of adjunctive aPDT as compared to SRP on clinical signs of CP in T2DM and smokers, no difference could be observed for all evaluated parameters (PD: Z=-0.81, P=0.41; CAL: Z=-0.19, P=0.84) except IL-1β (Z=4.57, P<0.001). Due to limited evidence, it remains debatable whether aPDT as an adjunct to SRP is effective in improving clinical, microbiological and immunological outcomes compared to SRP alone in T2DM and smokers with CP. Further well-designed, large-scale clinical trials with microbiological parameters and long follow up periods are needed in order to assess the efficacy of adjunctive aPDT in T2DM and cigarette smokers with CP. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Local adjunct effect of antimicrobial photodynamic therapy for the treatment of chronic periodontitis in type 2 diabetics: split-mouth double-blind randomized controlled clinical trial.

    Science.gov (United States)

    Castro Dos Santos, Nídia Cristina; Andere, Naira Maria Rebelatto Bechara; Araujo, Cássia Fernandes; de Marco, Andrea Carvalho; Dos Santos, Lúcio Murilo; Jardini, Maria Aparecida Neves; Santamaria, Mauro Pedrine

    2016-11-01

    Diabetes has become a global epidemic. Its complications can have a significant impact on quality of life, longevity, and public health costs. The presence of diabetes might impair the prognosis of periodontal treatments due to its negative influence on wound healing. Antimicrobial photodynamic therapy (aPDT) is a local approach that can promote bacterial decontamination in periodontal pockets. The aim of this study was to investigate the local effect of adjunct aPDT to ultrasonic periodontal debridement (UPD) and compare it to UD only for the treatment of chronic periodontitis in type 2 diabetic patients. Twenty type 2 diabetic patients with moderate to severe generalized chronic periodontitis were selected. Two periodontal pockets with probing depth (PD) and clinical attachment level (CAL) ≥5 mm received UPD only (UPD group) or UPD plus adjunct aPDT (UPD + aPDT group). Periodontal clinical measures were collected and compared at baseline and 30, 90, and 180 days. After 180 days of follow-up, there were statistically significant reductions in PD from 5.75 ± 0.91 to 3.47 ± 0.97 mm in the UPD group and from 6.15 ± 1.27 to 3.71 ± 1.63 mm in the UPD + aPDT group. However, intergroup analysis did not reveal statistically significant differences in any of the evaluated clinical parameters (p > 0.05). The adjunct application of aPDT to UPD did not present additional benefits for the treatment of chronic periodontitis in type 2 diabetic patients. The ClinicalTrials.gov identifier of the present study is NCT02627534.

  16. Effectiveness of adjunctive antimicrobial photodynamic therapy in reducing peri-implant inflammatory response in individuals vaping electronic cigarettes: A randomized controlled clinical trial.

    Science.gov (United States)

    Al Rifaiy, Mohammed Q; Qutub, Osama A; Alasqah, Mohammed N; Al-Sowygh, Zeyad H; Mokeem, Sameer A; Alrahlah, Ali

    2018-06-01

    There are no studies that have assessed the effectiveness of antimicrobial photodynamic therapy (aPDT) in reducing peri-implant inflammatory response in individuals vaping electronic cigarettes (e-cigs). This study explored the effectiveness of aPDT as an adjunct to mechanical debridement (MD) in the treatment of peri-implant mucositis (p-iM) in individuals vaping e-cigs. Vaping individuals with p-iM were divided into 2 groups: (a) Group-I: receiving MD with aPDT (test group); and (b) Group-II: MD only (control group). Peri-implant inflammatory parameters including plaque index (PI), bleeding on probing (BoP), and pocket depth (PD) were assessed at baseline and 12-weeks follow-up. Inter- and intra-group comparisons were made using Mann-Whitney U test and Wilcoxon signed ranks test. P-value vaping individuals in groups I and II were 33.6 ± 2.8 and 35.4 ± 2.1 years, respectively. Mean daily frequency of vaping e-cigs in groups I and II was 7.3 ± 0.9 and 5.9 ± 1.0 whereas mean duration of vaping e-cigs was 4.8 ± 1.5 and 4.1 ± 1.3 years respectively. There was no significant difference between groups at baseline. There was significant improvement in PI (p vaping e-cigs. The findings of the present study should be considered preliminary and interpreted with caution. Further randomized clinical trials should be performed in order to obtain strong conclusions. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Photodynamic Cancer Therapy - Recent Advances

    International Nuclear Information System (INIS)

    Abrahamse, Heidi

    2011-01-01

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  18. Photodynamic therapy for periodontal disease

    Science.gov (United States)

    Weersink, Robert A.

    2002-05-01

    Periodontal disease is a family of chronic inflammatory conditions caused by bacterial infections.' It is manifested in red, swollen gingiva (gums) and can lead to destruction of the connective tissue and bone that hold teeth in place. Conventional treatments typically require some form of invasive surgery, depending on the disease stage at time of detection. Photodynamic Therapy (PDT) is the use of light-activated drugs (photosensitizers) for treatment of a variety of conditions 2 such as solid tumors, pre-malignancies, macular degeneration and actinic keratitis. There have been a number of studies of PDT as an antibacterial agent. 3'4 Depending on the photosensitizer and strain of bacteria, significant killing (several LOGS) can be achieved.

  19. Evaluation of the efficacy of photodynamic antimicrobial therapy using a phenothiazine compound and Laser (λ=660ηm) on the interface: macrophage vs S. aureus

    Science.gov (United States)

    de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Pires-Santos, Gustavo M.; Sampaio, Fernando José P.; Zanin, Fátima Antônia A.; Pinheiro, Antônio L. B.

    2015-03-01

    Nowadays photodynamic inactivation has been proposed as an alternative treatment for localized bacterial infections as a response to the problem of antibiotic resistance. Much is already known about the photodynamic inactivation of microorganisms: both antibiotic-sensitive and -resistant strains can be successfully photoinactivated and there is the additional advantage that repeated photosensitization of bacterial cells does not induce a selection of resistant strains. Staphylococcus spp. are opportunistic microorganisms known for their capacity to develop resistance against antimicrobial agents. The emergence of resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) poses a major challenge to healthcare. MRSA is a major cause of hospital-acquired infection throughout the world and is now also prevalent in the community as well as nursing and residential homes. The aim of this study was to evaluate the phagocytic function of macrophages J774 against S. aureus in the presence and absence of AmPDT with phenothiazine compound (12.5 μg/mL) and low level laser (λ=660nm, 12 J/cm²). Experimental groups: Control group (L-P-), Phenothiazine group (L-P+) Laser group (L+P-), AmPDT group (L+P+).The tests presented in this study were performed in triplicate. This study showed that AmPDT induced bacterial death in about 80% as well as increasing phagocytic capacity of macrophages by approximately 20% and enhanced the antimicrobial activity by approximately 50% compared to the control group and enabling more intense oxidative burst.

  20. Type I and Type II mechanisms of antimicrobial photodynamic therapy: an in vitro study on gram-negative and gram-positive bacteria.

    Science.gov (United States)

    Huang, Liyi; Xuan, Yi; Koide, Yuichiro; Zhiyentayev, Timur; Tanaka, Masamitsu; Hamblin, Michael R

    2012-08-01

    Antimicrobial photodynamic therapy (APDT) employs a non-toxic photosensitizer (PS) and visible light, which in the presence of oxygen produce reactive oxygen species (ROS), such as singlet oxygen ((1) O(2), produced via Type II mechanism) and hydroxyl radical (HO(.), produced via Type I mechanism). This study examined the relative contributions of (1) O(2) and HO(.) to APDT killing of Gram-positive and Gram-negative bacteria. Fluorescence probes, 3'-(p-hydroxyphenyl)-fluorescein (HPF) and singlet oxygen sensor green reagent (SOSG) were used to determine HO(.) and (1) O(2) produced by illumination of two PS: tris-cationic-buckminsterfullerene (BB6) and a conjugate between polyethylenimine and chlorin(e6) (PEI-ce6). Dimethylthiourea is a HO(.) scavenger, while sodium azide (NaN(3)) is a quencher of (1) O(2). Both APDT and killing by Fenton reaction (chemical generation of HO(.)) were carried out on Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa). Conjugate PEI-ce6 mainly produced (1) O(2) (quenched by NaN(3)), while BB6 produced HO(.) in addition to (1) O(2) when NaN(3) potentiated probe activation. NaN(3) also potentiated HPF activation by Fenton reagent. All bacteria were killed by Fenton reagent but Gram-positive bacteria needed a higher concentration than Gram-negatives. NaN(3) potentiated Fenton-mediated killing of all bacteria. The ratio of APDT killing between Gram-positive and Gram-negative bacteria was 2 or 4:1 for BB6 and 25:1 for conjugate PEI-ce6. There was a NaN(3) dose-dependent inhibition of APDT killing using both PEI-ce6 and BB6 against Gram-negative bacteria while NaN(3) almost failed to inhibit killing of Gram-positive bacteria. Azidyl radicals may be formed from NaN(3) and HO(.). It may be that Gram-negative bacteria are more susceptible to HO(.) while Gram-positive bacteria are more susceptible to (1) O(2). The differences in Na

  1. Biophysical aspects of photodynamic therapy.

    Science.gov (United States)

    Juzeniene, Asta; Nielsen, Kristian Pagh; Moan, Johan

    2006-01-01

    Over the last three decades photodynamic therapy (PDT) has been developed to a useful clinical tool, a viable alternative in the treatment of cancer and other diseases. Several disciplines have contributed to this development: chemistry in the development of new photosensitizing agents, biology in the elucidation of cellular processes involved in PDT, pharmacology and physiology in identifying the mechanisms of distribution of photosensitizers in an organism, and, last but not least, physics in the development of better light sources, dosimetric concepts and construction of imaging devices, optical sensors and spectroscopic methods for determining sensitizer concentrations in different tissues. Physics and biophysics have also helped to focus on the role of pH for sensitizer accumulation, dose rate effects, oxygen depletion, temperature, and optical penetration of light of different wavelengths into various types of tissue. These are all important parameters for optimally effective PDT. The present review will give a brief, physically based, overview of PDT and then discuss some of the main biophysical aspects of this therapeutic modality.

  2. Photodynamic therapy for skin cancer

    Science.gov (United States)

    Panjehpour, Masoud; Julius, Clark E.; Hartman, Donald L.

    1996-04-01

    Photodynamic therapy was used to treat 111 lesions in 27 cases with squamous and basal cell carcinoma. There were 82 squamous cell carcinomas and 29 basal cell carcinomas. Photofrin was administered intravenously at either 1.0 mg/kg or 0.75 mg/kg. An argon/dye laser was used to deliver 630 nm light to the lesion superficially at either 215 J/cm2 or 240 J/cm2. In some cases the laser light was delivered both superficially and interstitially. The laser light was delivered two to four days after the Photofrin injection. There were 105 complete responses and 5 partial responses. One patient was lost to follow-up. Among partial responses were basal cell carcinoma on the tip of the nose and morphea basal cell carcinoma of the left cheek. Another partial response occurred in a basal cell carcinoma patient where insufficient margins were treated due to the proximity to the eye. When 0.75 mg/kg drug dose was used, the selectivity of tumor necrosis was improved. Decreased period of skin photosensitivity was documented in some cases.

  3. Dye Sensitizers for Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Harold S. Freeman

    2013-03-01

    Full Text Available Photofrin® was first approved in the 1990s as a sensitizer for use in treating cancer via photodynamic therapy (PDT. Since then a wide variety of dye sensitizers have been developed and a few have been approved for PDT treatment of skin and organ cancers and skin diseases such as acne vulgaris. Porphyrinoid derivatives and precursors have been the most successful in producing requisite singlet oxygen, with Photofrin® still remaining the most efficient sensitizer (quantum yield = 0.89 and having broad food and drug administration (FDA approval for treatment of multiple cancer types. Other porphyrinoid compounds that have received approval from US FDA and regulatory authorities in other countries include benzoporphyrin derivative monoacid ring A (BPD-MA, meta-tetra(hydroxyphenylchlorin (m-THPC, N-aspartyl chlorin e6 (NPe6, and precursors to endogenous protoporphyrin IX (PpIX: 1,5-aminolevulinic acid (ALA, methyl aminolevulinate (MAL, hexaminolevulinate (HAL. Although no non-porphyrin sensitizer has been approved for PDT applications, a small number of anthraquinone, phenothiazine, xanthene, cyanine, and curcuminoid sensitizers are under consideration and some are being evaluated in clinical trials. This review focuses on the nature of PDT, dye sensitizers that have been approved for use in PDT, and compounds that have entered or completed clinical trials as PDT sensitizers.

  4. Photodynamic therapy for hair removal

    Directory of Open Access Journals (Sweden)

    Mohamed H. M. Ali

    2013-05-01

    Full Text Available Background: Unwanted hair is one of the most common medical problems affecting women of reproductive age inducing a lot of psychological stress and threatening their femininity and self-esteem. Old methods of removing unwanted hair include shaving, waxing, chemical depilation, and electrolysis, all of which have temporary results. However laser-assisted hair removal is the most efficient method of long-term hair removal currently available. It is desirable to develop a reduced cost photodynamic therapy (PDT system whose properties should include high efficiency and low side-effects. Method: Mice skin tissues were used in this study and divided into six groups such as controls, free methylene blue (MB incubation, liposome methylene blue (MB incubation, laser without methylene blue (MB, free methylene blue (MB for 3 and 4 hrs and laser, liposome methylene blue (MB for 3 hrs and laser. Methylene blue (MBwas applied to wax epilated areas. The areas were irradiated with CW He-Ne laser system that emits orange-red light with wavelength 632.8 nm and 10 mW at energy density of 5 J/ cm2 for 10 minutes. The UV-visible absorption spectrum was collected by Cary spectrophotometer. Results: Methylene blue (MB is selectively absorbed by actively growing hair follicles due to its cationic property. Methylene blue (MBuntreated sections showed that hair follicle and sebaceous gland are intact and there is no change due to the laser exposure. Free methylene blue (MB sections incubated for 3 hrs showed that He:Ne laser induced destruction in hair follicles, leaving an intact epidermis. Treated section with free methylene blue (MB for 4 hrs showed degeneration and necrosis in hair follicle, leaving an intact epidermis. Liposomal methylene blue (MB sections incubated for 3 hrs showed He:Ne laser induced destruction in hair follicles with intradermal leucocytic infiltration. Conclusions: Low power CW He:Ne laser and methylene blue (MB offered a successful PDT system

  5. Scope of photodynamic therapy in periodontics

    OpenAIRE

    Vivek Kumar; Jolly Sinha; Neelu Verma; Kamal Nayan; C S Saimbi; Amitandra K Tripathi

    2015-01-01

    Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT) is...

  6. Photodynamic therapy for recurrent respiratory papillomatosis.

    Science.gov (United States)

    Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M

    2014-06-05

    Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.   We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23

  7. INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR METASTATIC PERITONEAL TUMORS

    Directory of Open Access Journals (Sweden)

    E. A. Suleimanov

    2016-01-01

    Full Text Available This review is devoted to the cytoreductive treatment of malignant tumors of the abdominal organs. The actuality of the issue is determined both by increase of the incidence of abdominal cancer in Russia and in majority of developed countries and by high rate diagnosis on late stages of disease. The methods of treatment of peritoneal carcinomatosis, based on possible effects on the secondary peritoneal tumors after surgical cytoreduction to reduce the risk of local recurrence and disease progression are described. These methods of additional intraoperative specific antitumor action include intraoperative radiation therapy, hyperthermic intraperitoneal chemotherapy, intraoperative photodynamic therapy characterized by differences in difficulty of performance, mechanisms of effect on tumor and healthy tissues, efficiency. Benefits, opportunities and possibilities of application of intraoperative photodynamic therapy (IOPDT for secondary peritoneal tumors are described in details, the results of a number of domestic and foreign clinical studies are shown, the successful application of intraoperative photodynamic therapy in clinical oncology, which allows reducing the risk of secondary tumor lesions of the peritoneum significantly, is demonstrated. Photodynamic therapy – a method with high efficiency and almost no side effects and complications, based on the ability of photosensitizer to accumulate selectively and retain in the high proliferative tissues. The advantages of this type of treatment of patients with peritoneal carcinomatosis are a selective effect on the peritoneal carcinomatosis and on visually detected tumor tissue, high efficiency in patients with malignant tumors of the abdominal cavity and pelvis combined with surgical cytoreduction, minimal effect on normal organs and tissues of the patient, well tolerated procedure.

  8. Photodynamic therapy in treatment of severe oral lichen planus.

    Science.gov (United States)

    Rabinovich, O F; Rabinovich, I M; Guseva, A V

    2016-01-01

    The aim of the study was to elaborate the rationale for the application of photodynamic therapy in complex treatment of patient with severe oral lichen planus. Complex clinical and laboratory examination and treatment was performed in 54 patients divided on 3 groups. Diagnosis of oral lichen planus was based on clinical, histological and immunohistochemical features. Group 1 received standard treatment, in the second group photodynamic therapy was conducted in addition to conventional treatment, patients in the third group received only photodynamic therapy. The study results proved photodynamic therapy to be useful tool in complex treatment of severe oral lichen planus.

  9. Efficacy of the photodynamic antimicrobial therapy (PACT) with the use of methylene blue associated with the λ660nm laser in Leishmania (Leishmania) amazonesis: in vitro study

    Science.gov (United States)

    Pires-Santos, Gustavo M.; Marques, Aparecida M. C.; Alves, Eliomara S. S.; Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Rosa, Cristiane B.; Colombo, Fabio; Pinheiro, Antônio L. B.; Vannier-Santos, Marcos A.

    2012-03-01

    The present studied evaluated the in vitro effects of PDT on Leishmania (Leishmania) amazonensis promastigotes. For this examination L. amazonensis promastigotes, stain Josefa, were used and maintained in Warren media supplement with fetal bovine serum at 26°C for 96 hours. A viability curve was accomplished using different concentrations of methylene blue photosensitizer associated to red laser light in order to obtain the most effective interaction to inhibit the parasite's growth. Two pre-irradiation periods, 5 and 30 minutes, were evaluated and the promastigotes were counted by colorimetry. On fluorescence microscopy the autophagic processes and reactive oxygen species were detected. Promastigotes treated with Photodynamic Therapy (PDT) by concentrations of 5 and 0,315ug/mL, presented cellular proliferation inhibition when compared to the control. In the first condition, the cells had structural alterations such as truncated cells, cells with two flagella, bleb formation and cells body deformation, while none of these modifications could be visualized in the control group. When analyzed through fluorescence microscopy, the promastigotes treated were positives for free radicals immediately after light application and also 1 hour after treatment presenting signs of autophagia. PDT on L. (L.) amazonensis is effective causing alterations that can help elucidate the mechanisms of the parasite's death when treated with methilene

  10. An effective zinc phthalocyanine derivative for photodynamic antimicrobial chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhuo, E-mail: zchen@fjirsm.ac.cn [State Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Zhou, Shanyong; Chen, Jincan [State Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Li, Linsen [Department of Biochemistry, Shenyang Medical College, Shenyang, Liaoning 110034 (China); Hu, Ping; Chen, Song [State Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Huang, Mingdong, E-mail: mhuang@fjirsm.ac.cn [State Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China)

    2014-08-01

    Bacterial infection is a common clinical problem. The emergence of antibiotic resistant bacteria posts a severe challenge to medical practice worldwide. Photodynamic antimicrobial chemotherapy (PACT) uses laser light at specific wavelength to activate oxygen molecule in the human tissue into reactive oxygen species as antimicrobial agent. This activation of oxygen by laser light is mediated through a photosensitizer. Two key properties for potent photosensitizer are its absorbance of light in the infrared region (630–700 nm), which promotes tissue penetration depth, and the selective accumulation on bacteria instead of human tissue. We herein report a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys){sub 5}) and its antimicrobial effects in vitro and in an animal infection model. This photosensitizer has strong capability to kill bacteria at 670 nm. Chemically, it is a water-soluble and cationic photosensitizer carrying positive charge under physiological pH, and can specifically target to bacteria which usually bears negative charges on its surface. Compared with anionic ZnPc counterparts, ZnPc-(Lys){sub 5} shows a higher phototoxicity toward bacteria. PACT studies of ZnPc-(Lys){sub 5} in experimental infection animal model showed a significant bacteria inhibition compared to controls, and high selectivity of ZnPc-(Lys){sub 5} toward bacteria. These findings suggest ZnPc-(Lys){sub 5} is a promising antimicrobial photosensitizer for the treatment of infectious diseases. - Highlights: • Photodynamic antimicrobial chemotherapy (PACT) with water-soluble zinc phthalocyanine derivative offers a promising measure to deal with antibiotic resistance of bacteria. • The use of portable LED light sources that are battery-powered and with low cost may make possible the deployment of systems that can be used for wound decontamination. • ZnPc-(Lys){sub 5} is a potent photosensitizer for treatment of infectious diseases.

  11. An effective zinc phthalocyanine derivative for photodynamic antimicrobial chemotherapy

    International Nuclear Information System (INIS)

    Chen, Zhuo; Zhou, Shanyong; Chen, Jincan; Li, Linsen; Hu, Ping; Chen, Song; Huang, Mingdong

    2014-01-01

    Bacterial infection is a common clinical problem. The emergence of antibiotic resistant bacteria posts a severe challenge to medical practice worldwide. Photodynamic antimicrobial chemotherapy (PACT) uses laser light at specific wavelength to activate oxygen molecule in the human tissue into reactive oxygen species as antimicrobial agent. This activation of oxygen by laser light is mediated through a photosensitizer. Two key properties for potent photosensitizer are its absorbance of light in the infrared region (630–700 nm), which promotes tissue penetration depth, and the selective accumulation on bacteria instead of human tissue. We herein report a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys) 5 ) and its antimicrobial effects in vitro and in an animal infection model. This photosensitizer has strong capability to kill bacteria at 670 nm. Chemically, it is a water-soluble and cationic photosensitizer carrying positive charge under physiological pH, and can specifically target to bacteria which usually bears negative charges on its surface. Compared with anionic ZnPc counterparts, ZnPc-(Lys) 5 shows a higher phototoxicity toward bacteria. PACT studies of ZnPc-(Lys) 5 in experimental infection animal model showed a significant bacteria inhibition compared to controls, and high selectivity of ZnPc-(Lys) 5 toward bacteria. These findings suggest ZnPc-(Lys) 5 is a promising antimicrobial photosensitizer for the treatment of infectious diseases. - Highlights: • Photodynamic antimicrobial chemotherapy (PACT) with water-soluble zinc phthalocyanine derivative offers a promising measure to deal with antibiotic resistance of bacteria. • The use of portable LED light sources that are battery-powered and with low cost may make possible the deployment of systems that can be used for wound decontamination. • ZnPc-(Lys) 5 is a potent photosensitizer for treatment of infectious diseases

  12. Iridium complexes for the application of photodynamic therapy

    Directory of Open Access Journals (Sweden)

    SHI Min

    2015-10-01

    Full Text Available Photodynamic therapy can destruct tumor cells by singlet oxygen which is generated via a photodynamic reaction of the photosensitizer under a specfic excitation wavelength.Due to the heavy atom effect of metal iridium,iridiumcomplexes are excited by suitable light and then reach their excited triple state through intersystem crossing.The excited iridium complexes transfer energy to oxygen molecules to produce singlet oxygen for photodynamic therapy.

  13. Photodynamic therapy of cervical intraepithelial neoplasia

    Science.gov (United States)

    Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

  14. Photodynamic therapy using aminolevulinic acid (ALA)

    Science.gov (United States)

    Bachor, Ruediger; Reich, Ella D.; Miller, Kurt; Hautmann, Richard E.

    1994-03-01

    Photodynamic therapy (PDT) is a treatment modality for a variety of cancers. Since no ideal photosensitizer is available yet, new photosensitizers are being sought. A new concept of PDT is the use of endogenous photosensitizers. ALA is a metabolite in heme synthesis. It is a precursor of protoporphyrin IX, a potent photosensitizer. After administration of ALA it is transformed by the cells to protoporphyrin IX. The goal of our study was to examine dark toxicity of ALA and its phototoxic potential in two different human cell lines.

  15. Absence of bacterial resistance following repeat exposure to photodynamic therapy

    Science.gov (United States)

    Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.

    2009-06-01

    The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

  16. The use of photodynamic therapy in the treatment of keratoacanthomas

    Directory of Open Access Journals (Sweden)

    V. N. Galkin

    2016-01-01

    Full Text Available The review is on treatment of keratoacanthomas using photodynamic therapy. The defining characteristic of keratoacanthoma among epithelial tumors is a rapid spontaneous regression in the case of typical keratoacanthoma and long-term persistence, recurrence and common malignant transformation to squamous cell carcinoma in the case of atypical keratoacanthoma. In recent years, photodynamic therapy which is an effective method of treatment of different types of cancer and pre-cancer diseases of the skin including actinic keratosis, Bowen’s disease, basal cell carcinoma, is increasingly used in clinical practice. There are few data for photodynamic therapy in the treatment of keratoacanthoma. The analysis of the literature shows that using of photodynamic therapy in the set of treatment modalities in patients with keratoacanthoma improves the efficacy and reduces the terms of the therapy. In all investigations except one there was complete tumor regression in 100% patients with keratoacanthoma who underwent photodynamic therapy. In one study complete tumor regression was observed in 66.7% of patients with atypical keratoacanthoma after photodynamic therapy. The follow-up of patients in all analyzed studies accounted for at least 2-3 years. During this time none of the patients had evidence for recurrence. This approach has minimal restrictions for application. Thus, photodynamic therapy may become a therapeutic alternative to surgical treatment of keratoacanthoma with good clinical and cosmetic results.

  17. Drug Carrier for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Tilahun Ayane Debele

    2015-09-01

    Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

  18. Combined Antimicrobial Activity of Photodynamic Inactivation and Antimicrobials–State of the Art

    Directory of Open Access Journals (Sweden)

    Agata Wozniak

    2018-05-01

    Full Text Available Antimicrobial photodynamic inactivation (aPDI is a promising tool for the eradication of life-threatening pathogens with different profiles of resistance. This study presents the state-of-the-art published studies that have been dedicated to analyzing the bactericidal effects of combining aPDI and routinely applied antibiotics in in vitro (using biofilm and planktonic cultures and in vivo experiments. Furthermore, the current paper reviews the methodology used to obtain the published data that describes the synergy between these antimicrobial approaches. The authors are convinced that even though the combined efficacy of aPDI and antimicrobials could be investigated with the wide range of methods, the use of a unified experimental methodology that is in agreement with antimicrobial susceptibility testing (AST is required to investigate possible synergistic cooperation between aPDI and antimicrobials. Conclusions concerning the possible synergistic activity between the two treatments can be drawn only when appropriate assays are employed. It must be noticed that some of the described papers were just aimed at determination if combined treatments exert enhanced antibacterial outcome, without following the standard methodology to evaluate the synergistic effect, but in most of them (18 out of 27 authors indicated the existence of synergy between described antibacterial approaches. In general, the increase in bacterial inactivation was observed when both therapies were used in combination.

  19. Scope of photodynamic therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Vivek Kumar

    2015-01-01

    Full Text Available Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT is a powerful laser-initiated photochemical reaction, involving the use of a photoactive dye (photosensitizer activated by light of a specific wavelength in the presence of oxygen. Application of PDT in periodontics such as pocket debridement, gingivitis, and aggressive periodontitis continue to evolve into a mature clinical treatment modality and is considered as a promising novel approach for eradicating pathogenic bacteria in periodontitis.

  20. Scope of photodynamic therapy in periodontics.

    Science.gov (United States)

    Kumar, Vivek; Sinha, Jolly; Verma, Neelu; Nayan, Kamal; Saimbi, C S; Tripathi, Amitandra K

    2015-01-01

    Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT) is a powerful laser-initiated photochemical reaction, involving the use of a photoactive dye (photosensitizer) activated by light of a specific wavelength in the presence of oxygen. Application of PDT in periodontics such as pocket debridement, gingivitis, and aggressive periodontitis continue to evolve into a mature clinical treatment modality and is considered as a promising novel approach for eradicating pathogenic bacteria in periodontitis.

  1. Different light sources in photodynamic therapy for use in photorejuvenation

    CSIR Research Space (South Africa)

    Van Kets, V

    2010-09-01

    Full Text Available Photodynamic therapy (PDT) has recently emerged as a treatment modality for photorejuvenation of the skin. This study is a preliminary investigation into the effect of different light sources to activate hypericin, a plant-derived photosensitizer...

  2. Photodynamic therapy: the role of paraptosis

    Science.gov (United States)

    Kessel, David; Cho, Won-Jin; Kim, Hyeong-Reh

    2018-02-01

    Apoptosis is a pathway to cell death frequently observed after photodynamic therapy (PDT). Sub-cellular photodamage to mitochondria, lysosomes, the ER, or combinations of these targets, can lead to apoptotic death. We have recently investigated another pathway to cell death after PDT termed `paraptosis'. This is characterized by extensive cytoplasmic vacuolization, does not involve caspase activation or nuclear fragmentation, requires a brief interval of continued protein synthesis and appears to derive from ER stress. Determinants and further characteristics of PDT-derived paraptosis are explored in the A549 non small-cell lung cancer cell line and in cells derived from head and neck cancer tissues. We provide evidence that ER photodamage and JNK pathway activation are involved in PDT-mediated paraptosis.

  3. Endoscopic and Photodynamic Therapy of Cholangiocarcinoma.

    Science.gov (United States)

    Meier, Benjamin; Caca, Karel

    2016-12-01

    Most patients with cholangiocarcinoma (CCA) have unresectable disease. Endoscopic bile duct drainage is one of the major objectives of palliation of obstructive jaundice. Stent implantation using endoscopic retrograde cholangiography is considered to be the standard technique. Unilateral versus bilateral stenting is associated with different advantages and disadvantages; however, a standard approach is still not defined. As there are various kinds of stents, there is an ongoing discussion on which stent to use in which situation. Palliation of obstructive jaundice can be augmented through the use of photodynamic therapy (PDT). Studies have shown a prolonged survival for the combinations of PDT and different stent applications as well as combinations of PDT and additional systemic chemotherapy. More well-designed studies are needed to better evaluate and standardize endoscopic treatment of unresectable CCA.

  4. Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds

    Directory of Open Access Journals (Sweden)

    Ester Caffarel-Salvador

    2015-09-01

    Full Text Available Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed “photodynamic antimicrobial chemotherapy” (PACT. In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez® AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1–2.5 mg/mL and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96

  5. INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR PERITONEAL MESOTHELIOMA

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2017-01-01

    Full Text Available Abstract Results of application of a new technology of intraoperative photodynamic therapy (IOFDT in patients with peritoneal mesothelioma developed at P. Herzen Moscow Oncology Research Institute are presented. The study included 8 patients. 3 patients underwent surgery in various amount: 1 – limited peritonectomy in the volume of tumor foci resection and resection of a large omentum, 1 – limited peritonectomy in the volume of tumor foci resection and atypical resection of the right lobe of the liver, 1 – only resection of the large omentum due to the fact that the tumor was located only in a large omentum and no signs of lesions of the parietal peritoneum was revealed by intraoperative revision. Surgical intervention in these patients was concluded by IOPDT. The remaining 5 patients underwent only IOPDT. After the treatment, two patients underwent additional courses of laparoscopic IOPDT. Of the 8 patients enrolled in the study, 4 died from the underlying disease, 1 from cardiovascular disease with recurrence of the disease, 1 from cardiovascular disease without signs of recurrence, 2 were monitored for 6 months and 146 months (12 years. Thus, in the group of patients with peritoneal mesothelioma, the maximum observation period was 146.44 months, the median survival was 48.4 months, the total specific 1-year survival was 85.7±13.2%, the three-year survival was 68.5±18.6%, the 5-year survival was 45.7 ± 22.4 %. The average life expectancy after treatment of patients with repeated courses of laparoscopic IOPDT was 87 months, without repeated courses – 35.8 months. Thus, life expectancy was higher in patients with repeated courses of laparoscopic IOPDT. Small sample size caused to the rarity of this pathology does not allow for statistically significant conclusions. However, the results of the study indicate the prospects of multi-course intraoperative photodynamic therapy in patients with peritoneal mesothelioma.

  6. Photodynamic therapy as a new approach in vulvovaginal candidiasis in murine model

    Science.gov (United States)

    Santi, Maria E.; Lopes, Rubia G.; Prates, Renato A.; Sousa, Aline; Ferreira, Luis R.; Fernandes, Adjaci U.; Bussadori, Sandra K.; Deana, Alessandro M.

    2015-02-01

    Vulvovaginal candidiasis is a common cause of vaginal infections. This study investigates the efficiency of antimicrobial photodynamic therapy (aPDT) against yeast cells in mice. Methylene blue (MB), malachite green (MG), and a special designed protoporphirin (PpNetNI) were used as photosensitizers. Female BALB-c mice were infected with Candida albicans ATCC 90028. PDT was applied with two different light sources, intravaginal and transabdominal. Vaginal washes were performed and cultivated for microbial quantification. Antimicrobial PDT was able to decrease microbial content with MB and PpNetNI (pcandidiasis.

  7. Advances in antimicrobial photodynamic inactivation at the nanoscale

    Science.gov (United States)

    Kashef, Nasim; Huang, Ying-Ying; Hamblin, Michael R.

    2017-08-01

    The alarming worldwide increase in antibiotic resistance amongst microbial pathogens necessitates a search for new antimicrobial techniques, which will not be affected by, or indeed cause resistance themselves. Light-mediated photoinactivation is one such technique that takes advantage of the whole spectrum of light to destroy a broad spectrum of pathogens. Many of these photoinactivation techniques rely on the participation of a diverse range of nanoparticles and nanostructures that have dimensions very similar to the wavelength of light. Photodynamic inactivation relies on the photochemical production of singlet oxygen from photosensitizing dyes (type II pathway) that can benefit remarkably from formulation in nanoparticle-based drug delivery vehicles. Fullerenes are a closed-cage carbon allotrope nanoparticle with a high absorption coefficient and triplet yield. Their photochemistry is highly dependent on microenvironment, and can be type II in organic solvents and type I (hydroxyl radicals) in a biological milieu. Titanium dioxide nanoparticles act as a large band-gap semiconductor that can carry out photo-induced electron transfer under ultraviolet A light and can also produce reactive oxygen species that kill microbial cells. We discuss some recent studies in which quite remarkable potentiation of microbial killing (up to six logs) can be obtained by the addition of simple inorganic salts such as the non-toxic sodium/potassium iodide, bromide, nitrite, and even the toxic sodium azide. Interesting mechanistic insights were obtained to explain this increased killing.

  8. Graphene-based nanovehicles for photodynamic medical therapy

    Directory of Open Access Journals (Sweden)

    Li Y

    2015-03-01

    Full Text Available Yan Li,1 Haiqing Dong,1 Yongyong Li,1 Donglu Shi1,2 1Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science (iNANO, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2The Materials Science and Engineering Program, Department of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA Abstract: Graphene and its derivatives such as graphene oxide (GO have been widely explored as promising drug delivery vehicles for improved cancer treatment. In this review, we focus on their applications in photodynamic therapy. The large specific surface area of GO facilitates efficient loading of the photosensitizers and biological molecules via various surface functional groups. By incorporation of targeting ligands or activatable agents responsive to specific biological stimulations, smart nanovehicles are established, enabling tumor-triggering release or tumor-selective accumulation of photosensitizer for effective therapy with minimum side effects. Graphene-based nanosystems have been shown to improve the stability, bioavailability, and photodynamic efficiency of organic photosensitizer molecules. They have also been shown to behave as electron sinks for enhanced visible-light photodynamic activities. Owing to its intrinsic near infrared absorption properties, GO can be designed to combine both photodynamic and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues and future aspects of photodynamic therapy research are addressed in this review. Keywords: graphene, nanovehicle, photodynamic therapy, photosensitizer, hyperthermia

  9. General principles of antimicrobial therapy.

    Science.gov (United States)

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

  10. Photodynamic therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Kamil H Nelke

    2014-02-01

    Full Text Available Photodynamic therapy (PDT is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells in different areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC, and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers, their use, and therapeutic advantages and disadvantages.

  11. Photodynamic Therapy for Malignant Brain Tumors.

    Science.gov (United States)

    Akimoto, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.

  12. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L.A. Muehlmann

    2011-08-01

    Full Text Available Photodynamic therapy is a well-established and clinically approved treatment for several types of cancer. Antineoplastic photodynamic therapy is based on photosensitizers, i.e., drugs that absorb photons translating light energy into a chemical potential that damages tumor tissues. Despite the encouraging clinical results with the approved photosensitizers available today, the prolonged skin phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and extended retention in the host organism shown by these drugs have stimulated researchers to develop new formulations for photodynamic therapy. In this context, due to their amphiphilic characteristic (compatibility with both hydrophobic and hydrophilic substances, liposomes have proven to be suitable carriers for photosensitizers, improving the photophysical properties of the photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes improve the efficiency and safety of antineoplastic photodynamic therapy, mainly by the classical phenomenon of extended permeation and retention. Therefore, the association of photosensitizers with liposomes has been extensively studied. In this review, both current knowledge and future perspectives on liposomal carriers for antineoplastic photodynamic therapy are critically discussed.

  13. Concepts and principles of photodynamic therapy as an alternative antifungal discovery platform

    Directory of Open Access Journals (Sweden)

    George eTegos

    2012-04-01

    Full Text Available Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative anti-fungal countermeasures. Photodynamic therapy was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Anti-fungal photodynamic therapy is an area of increasing interest, as research is advancing i to identify the photochemical and photophysical mechanisms involved in photoinactivation; ii to develop potent and clinically compatible photosensitizers; iii to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; iv to explore novel photosensitizer delivery platforms and v to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.

  14. Light emitting fabric technologies for photodynamic therapy.

    Science.gov (United States)

    Mordon, Serge; Cochrane, Cédric; Tylcz, Jean Baptiste; Betrouni, Nacim; Mortier, Laurent; Koncar, Vladan

    2015-03-01

    Photodynamic therapy (PDT) is considered to be a promising method for treating various types of cancer. A homogeneous and reproducible illumination during clinical PDT plays a determinant role in preventing under- or over-treatment. The development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of optical fiber into flexible structures could offer an interesting alternative. This paper aims to describe different methods proposed to develop Side Emitting Optical Fibers (SEOF), and how these SEOF can be integrated in a flexible structure to improve light illumination of the skin during PDT. Four main techniques can be described: (i) light blanket integrating side-glowing optical fibers, (ii) light emitting panel composed of SEOF obtained by micro-perforations of the cladding, (iii) embroidery-based light emitting fabric, and (iv) woven-based light emitting fabric. Woven-based light emitting fabrics give the best performances: higher fluence rate, best homogeneity of light delivery, good flexibility. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. New Photosensitizers for Photodynamic Therapy in Gastroenterology

    Directory of Open Access Journals (Sweden)

    SG Bown

    1999-01-01

    Full Text Available Most applications of photodynamic therapy (PDT in gastroenterology to date have used porfimer sodium as the photosensitizing agent. For destroying small lesions in the wall of the gastrointestinal tract in inoperable patients, it has proved to be most effective, but attempts to achieve circumferential mucosal ablation, as in the treatment of Barrett’s esophagus, have led to a high incidence of strictures, and all patients have cutaneous photosensitivity, which can last up to three months. Two new photosensitizers are of particular interest to gastroenterologists. PDT with metatetrahydroxyphenyl chlorin produces a similar biological effect as PDT with porfimer sodium, but the light doses required are much smaller, and cutaneous photosensitivity lasts only two to three weeks. Further, it can be used with percutaneous light delivery to destroy localized pancreatic cancers. The photosensitizing agent 5-amino levulinic acid, converted in vivo into the photoactive derivative protoporphyrin IX, sensitizes the mucosa much more than the underlying layers. This makes it feasible to destroy areas of abnormal mucosa without damaging the underlying muscle and is, therefore, better for treating Barrett’s esophagus. Detailed clinical studies are required to establish the real role of PDT with the use of these and other new photosensitizers.

  16. Photodynamic therapy: A new vista in management of periodontal diseases

    Directory of Open Access Journals (Sweden)

    Yogesh Doshi

    2010-01-01

    Full Text Available Aim: The purpose of this review was to evaluate the effectiveness of photodynamic therapy (PDT for periodontitis. This review also elucidates application of photodynamic therapy for noninvasive management of periodontitis without leading to bacterial resistance. Background: Periodontal diseases are one of the major causes of tooth loss in adults and are considered primarily an anaerobic bacterial infections caused by the so-called red complex species. Bacteria present in a biofilm community, enzymes, endotoxins, and other cytotoxic factors lead to tissue destruction and initiate chronic inflammation. Since many years pioneers have been working to provide logical and cost-effective therapy for management of periodontitis. Periodontal researchers have found that PDT is advantageous to suppress anaerobic bacteria. Clinical Significance: Applications of PDT in dentistry are growing rapidly. PDT application has an adjunctive benefit besides mechanical treatment at sites with difficult access. Necessity for flap surgery may be reduced, patient comfort may increase, and treatment time may decrease. The application of photosensitizing dyes and their excitation by visible light enables effective killing of periodonto-pathogens. The introduction of laser along with photosensitizers has brought a revolutionary change. Conclusion: The application of photodynamic therapy in management of periodontal diseases is very valuable. The therapy should be combined with nonsurgical periodontal therapy. Proper clinical application of photodynamic therapy can and will help patients who are systemically compromised and cannot undergo surgical therapy.

  17. Weather conditions and daylight-mediated photodynamic therapy

    DEFF Research Database (Denmark)

    Wiegell, S R; Fabricius, S; Heydenreich, J

    2013-01-01

    Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated methyl aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure for PDT. All daylight-PDT studies have been performed in the Nordic countries...

  18. Antimicrobial photodynamic therapy combined with periodontal treatment for metabolic control in patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial

    OpenAIRE

    Evangelista, Erika Elisabeth; Fran?a, Cristiane Miranda; Veni, Priscila; de Oliveira Silva, Tamires; Gon?alves, Rafael Moredo; de Carvalho, Ver?nica Franco; Deana, Alessandro Melo; Fernandes, Kristianne P S; Mesquita-Ferrari, Raquel A; Camacho, Cleber P; Bussadori, Sandra Kalil; Alvarenga, Let?cia Heineck; Prates, Renato Araujo

    2015-01-01

    Background The relationship between diabetes mellitus (DM) and periodontal disease is bidirectional. DM is a predisposing and modifying factor of periodontitis, which, in turn, worsens glycemic control and increases proteins found in the acute phase of inflammation, such as C-reactive protein. The gold standard for the treatment of periodontal disease is oral hygiene orientation, scaling and planing. Moreover, systemic antibiotic therapy may be employed in some cases. In an effort to minimize...

  19. Antimicrobial susceptibility of photodynamic therapy (UVA/riboflavin against Staphylococcus aureus Suscetibilidade antimicrobiana da terapia fotodinâmica (UVA/riboflavina contra Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Renata Tiemi Kashiwabuchi

    2012-12-01

    Full Text Available PURPOSE: To assess S. aureus in vitro viability after the exposure to ultraviolet light A (UVA and riboflavin (B2. METHODS: Samples of S. aureus in 96 well plates (in triplicate were exposed to riboflavin (B2 and ultraviolet light A (365 nm wavelength at a power density of 3 mW/cm², 8 mm spot diameter, for 30 minutes. Control groups were prepared as well in triplicate: blank control, ultraviolet light A only, riboflavin only and dead bacteria Control. The bacterial viability was measured using fluorescent microscopy. In order to investigate the occurrence of "viable but non-culturable" microorganisms after treatment, the cell viability was also investigated by plate culture procedure onto a broth medium. Statistical analysis was performed using the triplicate values from each experimental condition. RESULTS: No difference was observed among the treatment group and the control samples (p=1. CONCLUSION: The combination of riboflavin 0.1% and ultraviolet light A at 365 nm did not exhibit antimicrobial activity against oxacillin susceptible S. aureus.OBJETIVO: Avaliar a viabilidade celular de S. aureus in vitro após a exposição de riboflavina (B2 e luz ultravioleta A (UVA. MÉTODOS: Amostras de S. aureus colocadas em uma placa de 96 poços (em triplicata foram expostas a riboflavina 0,1% (B2 e luz ultravioleta (comprimento de onda de 365 nm poder de 3 mW/cm², 8 mm de diâmetro, por 30 minutos. Grupos controles foram também preparados em triplicata: controle branco, somente luz ultravioleta A, somente riboflavina e controle morto. A viabilidade bacteriana foi analisada usando microscópio de fluorescência. Para investigar a ocorrência de micro-organismos "viáveis porem não cultiváveis" a viabilidade celular foi avaliada utilizando-se placas de meio de cultivo bacteriano. Analise estatística foi realizada utilizando-se os valores obtidos em triplicata de cada grupo experimental. RESULTADOS: Nenhuma diferença foi observada entre o grupo

  20. Salvage photodynamic therapy for recurrent nasopharyngeal carcinoma.

    Science.gov (United States)

    Succo, Giovanni; Rosso, S; Fadda, G L; Fantini, M; Crosetti, Erika

    2014-06-01

    To evaluate the feasibility of photodynamic therapy (NP-PDT) in the palliative management of recurrent/persistent nasopharyngeal cancer (NFC). Six patients with persistent/recurrent NPC underwent PDT with palliative intent. NP-PDT was delivered by three different methods depending on the localization, size and depth of the lesion: type I NP-PDT: transnasal direct illumination of postero-superior recurrence; type II NP-PDT: transnasal direct illumination of the whole nasopharynx; type III NP-PDT: transoral direct or interstitial illumination of lateral recurrence. In this case, the ENT-magnetic navigation system (MNS) was extremely useful in identifying the tumor and its distance from the ICA. Both patients treated with NP-PDT type I are free from disease at 38 and 71 months after treatment; both patients treated with NP-PDT type II experienced further local and loco-regional recurrence of disease within 16 months; one died of the disease while the second underwent a second palliative treatment, NP-PDT type I, and is currently living with the disease; of the two patients who underwent NP-PDT type III, one died as a result of regional and systemic recurrence without local recurrence while the second experienced a superficial recurrence. He underwent a second NP-PDT type III treatment and is currently free from disease at 21 months. NP-PDT is a non-invasive and simple treatment modality that may have an important role in the treatment of selected cases of persistent/recurrent NPC in its early stage, not suitable for a conventional therapeutic protocol. Coupling NP-PDT with the ENT-MNS can be an effective strategy to obtain more precise light delivery within the tumor, particularly in lateral and parapharyngeal localization. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Photodynamic Therapy Plus Chemotherapy Compared with Photodynamic Therapy Alone in Hilar Nonresectable Cholangiocarcinoma.

    Science.gov (United States)

    Wentrup, Robert; Winkelmann, Nicola; Mitroshkin, Andrey; Prager, Matthias; Voderholzer, Winfried; Schachschal, Guido; Jürgensen, Christian; Büning, Carsten

    2016-05-23

    Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic chemotherapy is superior to PDT alone. We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1-year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC.

  2. A novel diode laser system for photodynamic therapy

    DEFF Research Database (Denmark)

    Samsøe, E.; Andersen, P. E.; Petersen, P.

    2001-01-01

    In this paper a novel diode laser system for photodynamic therapy is demonstrated. The system is based on linear spatial filtering and optical phase conjugate feedback from a photorefractive BaTiO3 crystal. The spatial coherence properties of the diode laser are significantly improved. The system...

  3. Nanobody-photosensitizer conjugates for targeted photodynamic therapy

    NARCIS (Netherlands)

    Heukers, Raimond; van Bergen en Henegouwen, P; Oliveira, Sabrina

    2014-01-01

    Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt

  4. Uniform irradiation of irregularly shaped cavities for photodynamic therapy

    NARCIS (Netherlands)

    Rem, A. I.; van Gemert, M. J.; van der Meulen, F. W.; Gijsbers, G. H.; Beek, J. F.

    1997-01-01

    It is difficult to achieve a uniform light distribution in irregularly shaped cavities. We have conducted a study on the use of hollow 'integrating' moulds for more uniform light delivery of photodynamic therapy in irregularly shaped cavities such as the oral cavity. Simple geometries such as a

  5. Identification of neutrophils as important effector cells in photodynamic therapy

    NARCIS (Netherlands)

    W.J.A. de Vree (Wil)

    2000-01-01

    textabstractPhotodynamic therapy (PDT) is a treatment modality, which is at present widely used on an experimental basis for the treatment of cancer patients. It is based on the light induced excitation of light sensitive chemical compounds localized in malignant tissue. These so-called

  6. An upconversion nanoparticle - Zinc phthalocyanine based nanophotosensitizer for photodynamic therapy

    NARCIS (Netherlands)

    Xia, L.; Kong, X.; Liu, X.; Tu, L.; Zhang, Y.; Chang, Y.; Liu, K.; Shen, D.; Zhao, H.; Zhang, H.

    2014-01-01

    Recent advances in NIR triggering upconversion-based photodynamic therapy have led to substantial improvements in upconversion-based nanophotosensitizers. How to obtain the high efficiency of singlet oxygen generation under low 980 nm radiation dosage still remains a challenge. A highly efficient

  7. The effects of photodynamic laser therapy in the treatment of marginal chronic periodontitis

    Science.gov (United States)

    Chifor, Radu; Badea, Iulia; Avram, Ramona; Chifor, Ioana; Badea, Mîndra Eugenia

    2016-03-01

    The aim of this study was to assess the effects of the antimicrobial photodynamic laser therapy performed during the treatment of deep periodontal disease by using 40 MHz high frequency ultrasonography. The periodontal data recorded during the clinical examination before each treatment session were compared with volumetric changes of the gingiva measured on periodontal ultrasound images. The results show a significant decrease of gingival tissue inflammation proved both by a significant decrease of bleeding on probing as well as by a decrease of the gingival tissues volume on sites where the laser therapy was performed. Periodontal tissues that benefit of laser therapy besides classical non-surgical treatment showed a significant clinical improvement of periodontal status. Based on these findings we were able to conclude that the antimicrobial photodynamic laser therapy applied on marginal periodontium has important anti-inflamatory effect. The periodontal ultrasonography is a method which can provide useful data for assessing the volume changes of gingival tissues, allowing a precise monitoring of marginal periodontitis.

  8. Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With Pseudomonas aeruginosa and Fusarium spp.

    Science.gov (United States)

    Aspiroz, C; Sevil, M; Toyas, C; Gilaberte, Y

    Photodynamic therapy (PDT) is a therapeutic modality with significant antimicrobial activity. We present 2 cases of chronic lower limb ulcers in which fungal and bacterial superinfection complicated management. PDT with methylene blue as the photosensitizer led to clinical and microbiological cure with no significant adverse effects. PDT with methylene blue is a valid option for the management of superinfected chronic ulcers, reducing the use of antibiotics and the induction of resistance. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. The synergistic effect of nanoparticles in photodynamic therapy and radiation therapy

    International Nuclear Information System (INIS)

    Chen Na; Tu Yu; Zhang Xuguang

    2010-01-01

    This paper describes a novel treatment: based on nanoparticles that combines radiotherapy and photodynamic therapy. With this approach, the application of traditional photodynamic therapies only to surface treatment can be solved, so that the therapeutic effect can be improved; the approach also could guarantee the effectiveness of treatment and reduce radiation doses, so it can effectively control the complications of radiotherapy, This new modality will open a new chapter for cancer therapy. (authors)

  10. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  11. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment

    DEFF Research Database (Denmark)

    Rubel, D M; Spelman, L; Murrell, D F

    2014-01-01

    BACKGROUND: Daylight photodynamic therapy (DL-PDT) of actinic keratosis (AK) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy (c-PDT), using methyl aminolevulinate (MAL) cream. OBJECTIVES: To demonstrate the efficacy and safety of DL-PDT vs. c...

  12. Photodynamic Antimicrobial Chemotherapy for Root Canal System Asepsis: A Narrative Literature Review

    Directory of Open Access Journals (Sweden)

    P. Diogo

    2015-01-01

    Full Text Available Aim. The aim of this comprehensive literature review was to address the question: Does photodynamic therapy (PDT improve root canal disinfection through significant bacterial reduction in the root canal system? Methodology. A comprehensive narrative literature review was performed to compare PDT effect with sodium hypochlorite as the comparative classical irrigant. Two reviewers independently conducted literature searches using a combination of medical subject heading terms and key words to identify relevant studies comparing information found in 7 electronic databases from January 2000 to May 2015. A manual search was performed on bibliography of articles collected on electronic databases. Authors were contacted to ask for references of more research not detected on the prior electronic and manual searches. Results. The literature search provided 62 titles and abstracts, from which 29 studies were related directly to the search theme. Considering all publications, 14 (48% showed PDT to be more efficient in antimicrobial outcome than NaOCl (0.5–6% concentration used alone and 2 (7% revealed similar effects between them. Toluidine blue and methylene blue are the most used photosensitizers and most commonly laser has 660 nm of wavelength with a 400 nm diameter of intracanal fiber. Conclusions. PDT has been used without a well-defined protocol and still remains at an experimental stage waiting for further optimization. The level of evidence available in clinical studies to answer this question is low and at high risk of bias.

  13. Candida albicans biofilm development in vitro for photodynamic therapy study

    International Nuclear Information System (INIS)

    Suzuki, Luis Claudio

    2009-01-01

    Photodynamic therapy (PDT) is a phototherapy based on the use of a photo sensitizer (PS) in the presence of low intensity light with resonant wavelength of absorption of the PS and biological systems that can raise awareness, generating reactive oxygen species. Studies show that PDT has a lethal effect on Candida albicans. The biofilm formed by C. albicans is the cause of infections associated with medical devices such as catheters, with a proven resistance to antifungal agents, and the removal of the catheter colonized almost always is necessary. However, few studies in literature report the behavior and response of biofilm organized by C. albicans against PDT. The aims of this study were to develop a methodology for in vitro biofilm formation of C. albicans, evaluate the sensitivity of the biofilm of C. albicans to antimicrobial photodynamic therapy using PS as the methylene blue (MB) and hypocrellin B: La +3 (HBL a+3 ) and analyze the biofilm by Optical Coherence Tomography (OCT). For biofilm formation, discs were made from elastomeric silicone catheters. The PS were dissolved in solution of PBS, and the MB had two different concentrations tested in the biofilm: 100μM and 1mM; HBLa +3 only one of 10μM. The irradiation of both dyes with the microorganism was done by two different LEDs, one with red emission at λ = 630nm ± 20nm and the other one blue emission at λ = 460nm ± 30nm. We performed a curve of survival fraction versus time of irradiation of each sample with biofilm and suspension of the microorganism in the yeast form to verify the susceptibility of the front PDT. The yeast showed 100% reduction using both PS, but at different times of irradiation (30s to HBLa +3 and 6 min for the MB at 100μM). When the therapy was applied in biofilm, the MB 100μM did not show any significant reduction, while at concentration of 1mM was reduced by 100% after 6 min of irradiation. The HBLa +3 biofilm group showed a lower reduction in the concentration of 10μM in

  14. Photodynamic Therapy in Treatment of Oral Lichen Planus

    Science.gov (United States)

    Mostafa, Diana; Tarakji, Bassel

    2015-01-01

    Oral lichen planus (OLP) is a relatively common chronic immunologic mucocutaneous disorder. Although there are many presenting treatments, some of them proved its failure. Recently, the use of photodynamic therapy (PDT) has been expanding due to its numerous advantages, as it is safe, convenient, and non-invasive and has toxic effect towards selective tissues. This article provides comprehensive review on OLP, its etiology, clinical features and recent non-pharmacological treatments. We also describe the topical PDT and its mechanisms. Our purpose was to evaluate the efficacy of PDT in treatment of OLP through collecting the data of the related clinical studies. We searched in PubMed website for the clinical studies that were reported from 2000 to 2014 using specific keywords: “photodynamic therapy” and “treatment of oral lichen planus”. Inclusion criteria were English publications only were concerned. In the selected studies of photodynamic treatment, adult patients (more than 20 years) were conducted and the OLP lesions were clinically and histologically confirmed. Exclusion criteria were classical and pharmacological treatments of OLP were excluded and also the using of PDT on skin lesions of lichen planus. We established five clinical studies in this review where all of them reported improvement and effectiveness of PDT in treatment of OLP lesions. The main outcome of comparing the related clinical studies is that the photodynamic is considered as a safe, effective and promising treatment modality for OLP. PMID:25883701

  15. Experience of treating late cerebral lungcancer metastasis using photodynamic therapy

    Directory of Open Access Journals (Sweden)

    A. I. Ryabova

    2013-01-01

    Full Text Available Treatment outcomes for a patient with solitary brain metastasis after long-term relapse-free follow-up of invasive lung carcinoma were presented. Brain metastasis without other signs of disease progression was diagnosed 10 years after combined modality treatment for stage II lung cancer. Removal of intracerebral metastasis with intraoperative photodynamic therapy was performed. Histology microspecimens of the primary tumor and metastasis were similar. No signs of disease progression in the brain 9 months after surgery were found. This case demonstrates that it is important to increase cancer suspicion for patients with long-term relapse-free follow-up. The use of intraoperative photodynamic therapy with photoditazine as a sensitizer in the treatment of cerebral metastases results in a favorable anti-tumor effect, thus improving life quality of patients

  16. Evaluation of photodynamic therapy (PDT) procedures using microfluidic system

    Energy Technology Data Exchange (ETDEWEB)

    Jedrych, Elzbieta, E-mail: ejedrych@ch.pw.edu.pl [Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 300-664 Warsaw (Poland); Pawlicka, Zuzanna; Chudy, Michal; Dybko, Artur; Brzozka, Zbigniew [Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 300-664 Warsaw (Poland)

    2011-01-10

    A hybrid PDMS/glass microfluidic system for evaluation of the efficiency of photodynamic therapy is presented. 5-aminolevulinic acid (ALA) was used as a precursor of photosensitizer. The geometry of the microdevice presented in this paper enables to test different concentrations of the photosensitizer in a single assay. The viability of the A549 cells was determined 24 h after PDT procedure (irradiation with light which induced a photosensitizer accumulated in carcinoma cells, {lambda} = 625 nm). The presented results confirmed the possibility to perform the photodynamic therapy process in vitro in microscale and the possibility to assess its effectiveness. Moreover, because two identical microstructures on a single chip were performed, the microchip can be used for examination simultaneously various cell lines (carcinoma and normal) or various photosensitizers.

  17. A Photosensitizer-Loaded DNA Origami Nanosystem for Photodynamic Therapy.

    Science.gov (United States)

    Zhuang, Xiaoxi; Ma, Xiaowei; Xue, Xiangdong; Jiang, Qiao; Song, Linlin; Dai, Luru; Zhang, Chunqiu; Jin, Shubin; Yang, Keni; Ding, Baoquan; Wang, Paul C; Liang, Xing-Jie

    2016-03-22

    Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.

  18. Photodynamic and antibiotic therapy impair the pathogenesis of Enterococcus faecium in a whole animal insect model.

    Directory of Open Access Journals (Sweden)

    José Chibebe Junior

    Full Text Available Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS. PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics. In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively. In the study of antimicrobial PDT, we verified that methylene blue (MB injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192. Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095 or vancomycin treatment alone (P = 0.0025, suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to

  19. Skin reactions after photodynamic therapy are unaffected by 839 nm photobiomodulation therapy

    DEFF Research Database (Denmark)

    Bay, Christiane; Vissing, Anne-Cathrine; Thaysen-Petersen, Daniel

    2017-01-01

    BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is associated with erythema and edema. Photobiomodulation (PBM) therapy may stimulate the skin recovery process. We investigated the potential of PBM to reduce PDT-induced skin reactions. STUDY DESIGN AND METHODS: Healthy volunteers (n = 20) were...

  20. The Recurrence and Cosmetic Results After Topical Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Alican Kazandı

    2009-12-01

    Full Text Available Background and Design: Photodynamic therapy (FDT is a photochemotherapy modality which is used frequently and effectively in the treatment of actinic keratosis, Bowen disease and basal cell carcinomas. This study was performed to determine cure rates, cosmetic outcome and recurrence rates after aminolevulinic acid (ALA-based photodynamic therapy for skin lesions showing complete response to treatment procedure. Material and Method: Sixty-eight patients (27 females and 41 males with 78 lesions were included in the study. Among them, 25 were actinic keratosis (AK, 8 were actinic cheilitis (AC, 30 were basal cell carcinomas (BCC, 3 were Bowen disease, 10 were intraepidermal epithelioma (IEE, one lesion was parapsoriasis and one lesion was verruca plantaris. Six to 8 hours after topical administration of ALA (20%, the lesions were exposed to light from a broad-band light source. Skin biopsy specimens were obtained from 74 lesions for histopathological control. Results: At the end of the second month of treatment, fifty-six (72% of seventy-eight lesions showed complete clinical response, whereas fourty-seven of 74 lesions (63.5% exhibited complete histopathological clearance. A total of 9 recurrences (16% was observed during a median follow-up of 36 months. Recurrence rates were 3 (14% in AK, 1 (17% in AC, 1 (8% in superficial BCC, 3 (75% nodular BCC and 1 (12.5% in IEE. Cosmetic outcome was excellent and good in 42 lesions (89%, fair in 3 lesions (6% and poor in 2 lesions (5%. Conclusion: Topical photodynamic therapy is a noninvasive, effective and cosmetic modality of treatment in the selected skin lesions, as an alternative to the conventional procedures.

  1. Photodynamic therapy as a novel treatment for halitosis in adolescents: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Lopes, Rubia Garcia; de Godoy, Camila Haddad Leal; Deana, Alessandro Melo; de Santi, Maria Eugenia Simões Onofre; Prates, Renato Araujo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Bussadori, Sandra Kalil

    2014-11-14

    Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% and systemic in 10% of cases. The unpleasant odor is mainly the result of volatile sulfur compounds produced by Gram-negative bacteria. However, it has recently been found that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the presence of amino acids, such as cysteine. Light, both with and without the use of chemical agents, has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by photosensitizing dye. The aim of the present study is to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using gas chromatography and microbiological analysis of coated tongue. A quantitative clinical trial will be carried out involving 60 adolescents randomly divided into the following groups: group 1 will receive treatment with a tongue scraper, group 2 will receive photodynamic therapy applied to the posterior two-thirds of the dorsum of the tongue, and group 3 will receive combined treatment (tongue scraper and photodynamic therapy). Gas chromatography (OralChromaTM) and microbiological analysis will be used for the diagnosis of halitosis at the beginning of the study. Post-treatment evaluations will be conducted at one hour and 24 hours after treatment. The statistical analysis will include the Shapiro-Wilk test for the determination of the distribution of the data. If normal distribution is demonstrated, analysis of variance followed by Tukey's test will be used to compare groups. The Kruskal-Wallis test followed by the Student-Newman-Keuls test will be used for data with non-normal distribution. Either the paired t-test or the Wilcoxon test will be used to compare data before and after treatment, depending on the distribution of the data. The

  2. Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection

    Science.gov (United States)

    Chen, Zhuo; Zhang, Yaxin; Wang, Dong; Li, Linsen; Zhou, Shanyong; Huang, Joy H.; Chen, Jincan; Hu, Ping; Huang, Mingdong

    2016-01-01

    Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-Lys). Compared with its anionic ZnPc counterpart, ZnPc-Lys showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-Lys was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.

  3. Three-dimensional illumination procedure for photodynamic therapy of dermatology

    Science.gov (United States)

    Hu, Xiao-ming; Zhang, Feng-juan; Dong, Fei; Zhou, Ya

    2014-09-01

    Light dosimetry is an important parameter that affects the efficacy of photodynamic therapy (PDT). However, the irregular morphologies of lesions complicate lesion segmentation and light irradiance adjustment. Therefore, this study developed an illumination demo system comprising a camera, a digital projector, and a computing unit to solve these problems. A three-dimensional model of a lesion was reconstructed using the developed system. Hierarchical segmentation was achieved with the superpixel algorithm. The expected light dosimetry on the targeted lesion was achieved with the proposed illumination procedure. Accurate control and optimization of light delivery can improve the efficacy of PDT.

  4. Liquid crystal nanoparticles for delivery of photosensitizers for photodynamic therapy

    Science.gov (United States)

    Nag, Okhil K.; Naciri, Jawad; Delehanty, James B.

    2018-02-01

    The main principle of photodynamic therapy (PDT) is to kill malignant cells by generation of reactive oxygen species (ROS). PDT appeared highly effective when ROS can be produced in subcellular location such as plasma membrane. The plasma membrane maintains the structural integrity of the cell and regulates multiple important cellular processes, such as endocytosis, trafficking, and apoptotic pathways, could be one of the best points to kill the cancer cells. Previously, we have developed a plasma membrane-targeted liquid crystal nanoparticle (LCNP) formulation that can be loaded with dyes or drugs. Here we highlight the utility of this LCNP for membrane targeted delivery and imaging for a photosensitizer (PS) for PDT applications.

  5. Cutaneous leishmaniasis responds to daylight-activated photodynamic therapy

    DEFF Research Database (Denmark)

    Enk, C D; Nasereddin, A; Alper, R

    2015-01-01

    BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Israel, with hundreds of new cases reported in recent years. Photodynamic therapy (PDT) is highly effective for treatment of CL, but requires equipment available only at specialized centres. Daylight-activated PDT (DA-PDT) abolishes the need...... application of a thick layer of 16% methyl aminolaevulinate and 30-min occlusion, the lesions were exposed to daylight for 2·5 h. Treatment sessions were repeated at weekly intervals until clinical and microbiological cure. Control lesions were either treated with cryotherapy or left untreated. RESULTS...

  6. Uniform irradiation of irregularly shaped cavities for photodynamic therapy.

    Science.gov (United States)

    Rem, A I; van Gemert, M J; van der Meulen, F W; Gijsbers, G H; Beek, J F

    1997-03-01

    It is difficult to achieve a uniform light distribution in irregularly shaped cavities. We have conducted a study on the use of hollow 'integrating' moulds for more uniform light delivery of photodynamic therapy in irregularly shaped cavities such as the oral cavity. Simple geometries such as a cubical box, a sphere, a cylinder and a 'bottle-neck' geometry have been investigated experimentally and the results have been compared with computed light distributions obtained using the 'radiosity method'. A high reflection coefficient of the mould and the best uniform direct irradiance possible on the inside of the mould were found to be important determinants for achieving a uniform light distribution.

  7. The Influence of Photodynamic Therapy on Tumor Cell S180

    Directory of Open Access Journals (Sweden)

    Pouran Sadat Tayebi

    2017-05-01

    Full Text Available Today cancer is the second important factor of the death in the world. Most of the cancer patients are treated with standard therapies, including surgery, radiation and/or chemotherapy. These standard therapies are most efficient on the primary tumor, but in the case of disseminated disease, they are often not effective. Treatment of disease that has disseminated from the primary tumor and metastasized to distant sites has promoted the investigation of immunotherapeutic strategies for cancer, and has been a major area of research over the last couple of decades. Chemotherapy and radiotherapy, standard therapies, are the main treatments for majority of cancer patients. Our studies demonstrate that ALA-HMME-PDT has a role in enhanced the quality of life and lengthens survival in mice infected by sarcoma 180. The reported method is hardly implemented but it possible in any clinical situation where PDT is needed. These therapies are most efficient in bearing the tumor in its first process of formation. Currently, the hot topic of discussion and research in the cancer arena is photodynamic Therapy (PDT. This type of therapy is an emerging channel of treatment that is very successful in eradicating cancer, with few side effects. The effectiveness of photodynamic therapy on the sarcoma treating process in mice by using ALA and HMME photosensitizers is investigated by this study. Many factors help us determine effectiveness of PDT including concentration of the sensitizer, absorption of light energy and accessibility of molecular oxygen in the target tissue during light irradiation, besides intrinsic sensitivity of target tissue.

  8. Impact of curcumin supersaturation in antibacterial photodynamic therapy-effect of cyclodextrin type and amount

    DEFF Research Database (Denmark)

    Hegge, A.B.; Nielsen, T.T.; Larsen, Kim Lambertsen

    2012-01-01

    Curcumin has been investigated as a potential photosensitizer (PS) in antimicrobial photodynamic therapy (aPDT). The phototoxic effect of curcumin is dependent on proper formulations of the compound because of the lipophilic nature of the molecule and the extremely low water solubility...... at physiological conditions. In the present study, the combination of curcumin with either a methylated β-cyclodextrin (CD) or polyethylene glycol-based β-CD or γ-CD polymers was investigated in aPDT using Escherichia coli (E. coli) and Enterococcus faecalis as model bacteria. Solutions with various...... supersaturation ratios of curcumin were prepared with the selected CD or CD polymers. The concept of supersaturation was then investigated as a mean to enhance the phototoxic effect of curcumin, especially toward the gram-negative bacteria E. coli. A high supersaturation ratio corresponded with high phototoxicity...

  9. Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

    Science.gov (United States)

    Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

    2014-11-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor-stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor-stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

  10. Factors related to pain during routine photodynamic therapy

    DEFF Research Database (Denmark)

    Miller, I M; Nielsen, J S; Lophaven, S

    2011-01-01

    between pain-reducing intervention and diagnosis, pre-treatment, gender or age was found. CONCLUSIONS: Pain-reducing intervention was required in 44% of the PDT treatments. Intervention was particularly required when treating lesions in areas suited for PDT therapy for cosmetic reasons such as the scalp......BACKGROUND: Pain may be a limiting factor in the use of photodynamic therapy (PDT). The consequences of the pain i.e. the resources spent on pain-intervention during routine PDT therapy are poorly described. OBJECTIVES: To describe the consequences of pain during PDT by describing the use of pain......-reducing interventions in routine use. We studied the frequency as well as level of pain-reducing intervention. METHODS: Descriptive data from PDT treated patients. The level of pain-reducing intervention was graded 0, no intervention; +, cold water spray and ++, pause or nerve block. RESULTS: Data from 983 PDT...

  11. Daylight photodynamic therapy for actinic keratosis

    DEFF Research Database (Denmark)

    Wiegell, Stine; Wulf, H C; Szeimies, R-M

    2011-01-01

    clinic visits and discomfort during therapy. In this article, we critically review daylight-mediated PDT, which is a simpler and more tolerable treatment procedure for PDT. We review the effective light dose, efficacy and safety, the need for prior application of sunscreen, and potential clinical scope...... of daylight-PDT. Three randomized controlled studies have shown that daylight-mediated PDT is an effective treatment of thin AKs. Daylight-mediated PDT is nearly pain-free and more convenient for both the clinics and patients. Daylight-mediated PDT is especially suited for patients with large field......-cancerized areas, which can easily be exposed to daylight. Further investigations are necessary to determine at which time of the year and in which weather conditions daylight-mediated PDT will be possible in different geographical locations....

  12. Photodynamic therapy of cancer — Challenges of multidrug resistance

    Directory of Open Access Journals (Sweden)

    Zheng Huang

    2015-01-01

    Full Text Available Photodynamic therapy (PDT of cancer is a two-step drug-device combination modality, which involves the topical or systemic administration of a photosensitizer followed by light illumination of cancer site. In the presence of oxygen molecules, the light illumination of photosensitizer (PS can lead to the generation of cytotoxic reactive oxygen species (ROS and consequently destroy cancer. Similar to many other anticancer therapies, PDT is also subject to intrinsic cancer resistance mediated by multidrug resistance (MDR mechanisms. This paper will review the recent progress in understanding the interaction between MDR transporters and PS uptake. The strategies that can be used in a clinical setting to overcome or bypass MDR will also be discussed.

  13. Diketopyrrolopyrrole-based carbon dots for photodynamic therapy.

    Science.gov (United States)

    He, Haozhe; Zheng, Xiaohua; Liu, Shi; Zheng, Min; Xie, Zhigang; Wang, Yong; Yu, Meng; Shuai, Xintao

    2018-06-01

    The development of a simple and straightforward strategy to synthesize multifunctional carbon dots for photodynamic therapy (PDT) has been an emerging focus. In this work, diketopyrrolopyrrole-based fluorescent carbon dots (DPP CDs) were designed and synthesized through a facile one-pot hydrothermal method by using diketopyrrolopyrrole (DPP) and chitosan (CTS) as raw materials. DPP CDs not only maintained the ability of DPP to generate singlet oxygen (1O2) but also have excellent hydrophilic properties and outstanding biocompatibility. In vitro and in vivo experiments demonstrated that DPP CDs greatly inhibited the growth of tumor cells under laser irradiation (540 nm). This study highlights the potential of the rational design of CDs for efficient cancer therapy.

  14. Photodynamic therapy: a review of applications in neurooncology and neuropathology

    Science.gov (United States)

    Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

    2015-06-01

    Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

  15. FLUORESCENCE DIAGNOSIS AND PHOTODYNAMIC THERAPY IN COMBINED TREATMENT OF CHOLANGIOCARCINOMA

    Directory of Open Access Journals (Sweden)

    A. A. Shiryaev

    2016-01-01

    Full Text Available The results of the pilot study of combined treatment for non-resectable cholangiocarcinoma complicated with obstructive jaundice are represented this paper. Method included percutaneous transhepatic biliary drainage, endoscopic fluorescence diagnosis, photodynamic therapy of tumor stricture, and stenting of bile ducts. Fourteen patients who underwent the treatment in the surgery department clinic of I.M. Sechenov First Moscow State Medical University were enrolled in the study. Fluorescence diagnosis and photodynamic therapy were carried out using photosensitizers photosens (0.5 mg/kg, fotolon (1 mg/kg, and radachlorin (1 mg/kg. The average light dose for one session was 115±5 J/cm2. Fluorescence diagnosis using endoscopic video-fluorescence system for endoscopy and minimally invasive surgery allowed to obtain videoassisted fluorescence image of the tumor and to measure level of photosensitizer fluorescence in tumor in all patients. Malignant tumor was confirmed by morphological study in 12 patients, biopsy of material for morphological study failed in 2 patients with Klatskin tumor. The preliminary results of combined minimally invasive treatment were assessed as promising. The survival time in 4 patients after treatment accounted for 21, 17, 13 and 11 months, respectively. For now 5 patients are under follow-up. Follow-up periods are 13 and 19 months in 2 of them and from 4 to 6 months in 3 of them. Five patients with multiple distant metastases before the treatment died in 3±1 months after therapy. The average lifetime in the treatment group is 9.5 months up to date, however the duration is expected to belonger because 5 of 14 patients are alive.

  16. Porphyrin-based Nanostructure-Dependent Photodynamic and Photothermal Therapies

    Science.gov (United States)

    Jin, Cheng S.

    This thesis presents the investigation of nanostructure-dependent phototherapy. We reviewed the liposomal structures for delivery of photosensitizers, and introduced a novel class of phototransducing liposomes called "porphysomes". Porphysomes are self-assembled from high packing density of pyropheophorbide alpha-conjugated phospholipids, resulting in extreme self-quenching of porphyrin fluorescence and comparable optical absorption to gold nanoparticles for high photothermal efficiency. We demonstrated this self-assembly of porphyrin-lipid conjugates converts a singlet oxygen generating mechanism (photodynamic therapy PDT activity) of porphyrin to photothermal mechanism (photothermal therapy PTT activity). The efficacy of porphysome-enhanced PTT was then evaluated on two pre-clinical animal models. We validated porphysome-enabled focal PTT to treat orthotopic prostate cancer using MRI-guided focal laser placement to closely mimic the current clinic procedure. Furthermore, porphysome-enabled fluorescence-guided transbronchial PTT of lung cancer was demonstrated in rabbit orthotopic lung cancer models, which led to the development of an ultra-minimally invasive therapy for early-stage peripheral lung cancer. On the other hand, the nanostructure-mediated conversion of PDT to PTT can be switched back by nanoparticle dissociation. By incorporating folate-conjugated phospholipids into the formulation, porphysomes were internalized into cells rapidly via folate receptor-mediated endocytosis and resulted in efficient disruption of nanostructures, which turned back on the photodynamic activity of densely packed porphyrins, making a closed loop of conversion between PDT and PTT. The multimodal imaging and therapeutic features of porphysome make it ideal for future personalized cancer treatments.

  17. Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser

    DEFF Research Database (Denmark)

    Togsverd-Bo, K; Haak, C S; Thaysen-Petersen, D

    2012-01-01

    Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field-cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy....

  18. Photodynamic therapy in dermatology: past, present, and future

    Science.gov (United States)

    Darlenski, Razvigor; Fluhr, Joachim W.

    2013-06-01

    Photodynamic therapy (PDT) is a noninvasive therapeutic method first introduced in the field of dermatology. It is mainly used for the treatment of precancerous and superficial malignant skin tumors. Today PDT finds new applications not only for nononcologic dermatoses but also in the field of other medical specialties such as otorhinolaryngology, ophthalmology, neurology, gastroenterology, and urology. We are witnessing a broadening of the spectrum of skin diseases that are treated by PDT. Since its introduction, PDT protocol has evolved significantly in terms of increasing method efficacy and patient safety. In this era of evidence-based medicine, it is expected that much effort will be put into creating a worldwide accepted consensus on PDT. A review on the current knowledge of PDT is given, and the historical basis of the method's evolution since its introduction in the 1900s is presented. At the end, future challenges of PDT are focused on discussing gaps that exist for research in the field.

  19. Photodynamic therapy: Theoretical and experimental approaches to dosimetry

    Science.gov (United States)

    Wang, Ken Kang-Hsin

    Singlet oxygen (1O2) is the major cytotoxic species generated during photodynamic therapy (PDT), and 1O 2 reactions with biological targets define the photodynamic dose at the most fundamental level. We have developed a theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O 2) consumption and transport and microscopic 1O 2 dose deposition during PDT in vivo. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O 2 saturation within vessels, irreversible photosensitizer degradation due to photobleaching, therapy-induced blood flow decrease and the microscopic distributions of 3O2 and 1O 2 dose deposition under various irradiation conditions. mTHPC, a promising photosensitizer for PDT, is approved in Europe for the palliative treatment of head and neck cancer. Using the theoretical model and informed by intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions for mTHPC-PDT. Our results demonstrate that the 1O 2 dose to the tumor volume does not track even qualitatively with long-term tumor responses. Thus, in this evaluation of mTHPC-PDT, any PDT dose metric that is proportional to singlet oxygen creation and/or deposition would fail to predict the tumor response. In situations like this one, other reporters of biological response to therapy would be necessary. In addition to the case study of mTHPC-PDT, we also use the mathematical model to simulate clinical photobleaching data, informed by a possible blood flow reduction during treatment. In a recently completed clinical trial at Roswell Park Cancer Institute, patients with superficial basal cell carcinoma received topical application of 5-aminolevulinic acid (ALA) and were irradiated with 633 nm light at 10-150 mW cm-2 . Protoporphyrin IX (PpIX) photobleaching in the lesion and the adjacent perilesion normal margin was monitored by

  20. The physics, biophysics and technology of photodynamic therapy

    International Nuclear Information System (INIS)

    Wilson, Brian C; Patterson, Michael S

    2008-01-01

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components-light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT. (topical review)

  1. The physics, biophysics and technology of photodynamic therapy.

    Science.gov (United States)

    Wilson, Brian C; Patterson, Michael S

    2008-05-07

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components -- light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

  2. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    Science.gov (United States)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  3. Colonic cancer cell polyamine synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    Briand, G.; Foultier, M.T.; Patrice, T.; Perret, C.; Combre, A.; Etourneau, M.J.

    1992-01-01

    PhotoDynamic Therapy is a new concept for cancer treatment based on the interaction between light and a sensitizer, hematoporphyrin derivative (HPD) selectively retained by tumor cells which becomes toxic after light exposure. This effect decreases cell growth, through complex pathways. The aim of this study was to determine whether cellular polyamines, Put (Putrescine), Spd (Spermidine) and Spm (Spermine) were modified after PDT or not. These cations of small molecular weight are essential for cell growth and differentiation of normal and neoplastic cells. In this study intracellular contents of Put, Spd and Spm were determined on 2 sublines of rat colonic cancer cells cloned from the same rat cancer and forming progressive (PROb) and regressive (REGb) tumors. (author). 12 refs., 2 figs

  4. Photoirradiation system for solid tumors in photodynamic therapy

    International Nuclear Information System (INIS)

    Pacheco, L.; Stolik, S.; Rosa, J.M. de la

    2012-01-01

    Photodynamic therapy (PDT) is a clinical procedure which induces cell death for destroying cancerous tissues mostly. This is accomplished by photochemical reaction produced by the combined action of three elements: photo sensitizer, light and oxygen. One aspect of the development of PDT is focused on the treatment of solid and deep tumors, where a set of delivering-light probes are placed into the tumor mass. However, this technique still has several challenges, for although certain parameters involved in the procedure may be adjusted, the complex geometry and non-homogeneity of a tumor difficult to establish the appropriate treatment planning. This paper addresses an overview of interstitial PDT and presents our proposal of photo irradiation system. (Author)

  5. Photodynamic therapy of cancer with the photosensitizer PHOTOGEM

    Science.gov (United States)

    Sokolov, Victor V.; Chissov, Valery I.; Filonenko, E. V.; Sukhin, Garry M.; Yakubovskaya, Raisa I.; Belous, T. A.; Zharkova, Natalia N.; Kozlov, Dmitrij N.; Smirnov, V. V.

    1995-01-01

    The first clinical trials of photodynamic therapy (PDT) in Russia were started in P. A. Hertzen Moscow Research Oncology Institute in October of 1992. Up to now, 61 patients with primary or recurrent malignant tumors of the larynx (3), trachea (1), bronchus (11), nose (1), mouth (3), esophagus (12), vagina and uterine cervix (3), bladder (2), skin (6), and cutaneous and subcutaneous metastases of breast cancer and melanomas (6) have been treated by PDT with the photosensitizer Photogem. At least partial tumor response was observed in all of the cases, but complete remission indicating no evident tumors has been reached in 51% of the cases. Among 29 patients with early and first stage cancer 14 patients had multifocal tumors. Complete remission of tumors in this group reached 86%.

  6. The physics, biophysics and technology of photodynamic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Brian C [Division of Biophysics and Bioimaging, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9 (Canada); Patterson, Michael S [Department of Medical Physics, Juravinski Cancer Centre and Department of Medical Physics and Applied Radiation Sciences, McMaster University, 699 Concession Street, Hamilton, ON L8V 5C2 (Canada)], E-mail: wilson@uhnres.utoronto.ca, E-mail: mike.patterson@jcc.hhsc.ca

    2008-05-07

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components-light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT. (topical review)

  7. Structural and functional imaging for vascular targeted photodynamic therapy

    Science.gov (United States)

    Li, Buhong; Gu, Ying; Wilson, Brian C.

    2017-02-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

  8. Endodontic treatment associated with photodynamic therapy: Case report.

    Science.gov (United States)

    Firmino, Ramon Targino; Brandt, Lorenna Mendes Temóteo; Ribeiro, Gustavo Leite; Dos Santos, Katia Simone Alves; Catão, Maria Helena Chaves de Vasconccelos; Gomes, Daliana Queiroga de Castro

    2016-09-01

    The complete elimination of bacteria inside the root canal is a difficult task, and inconsistent removal of the innermost layer of contaminated dentin leaves bacteria behind. PDT is an adjunct to conventional endodontic treatment due to its potential to reduce bacteria and its biocompatibility. Report a case of endodontic treatment associated with Photodynamic Therapy (PDT). A patient with chronic dentoalveolar abscess with radiolucent lesion next to the apexes of teeth 11 and 21 was submitted to conventional endodontic treatment associated with PDT. The canals were filled after two PDT sessions with an interval of 15days between applications. After six months, total regression of apical periodontitis and no fistula or associated symptoms were observed. The treatment proposed is a viable option for the clinician as it is easy to perform, has relatively low-cost and allows the improvement of symptoms in a short period of time. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Malignant pleural mesothelioma segmentation for photodynamic therapy planning.

    Science.gov (United States)

    Brahim, Wael; Mestiri, Makram; Betrouni, Nacim; Hamrouni, Kamel

    2018-04-01

    Medical imaging modalities such as computed tomography (CT) combined with computer-aided diagnostic processing have already become important part of clinical routine specially for pleural diseases. The segmentation of the thoracic cavity represents an extremely important task in medical imaging for different reasons. Multiple features can be extracted by analyzing the thoracic cavity space and these features are signs of pleural diseases including the malignant pleural mesothelioma (MPM) which is the main focus of our research. This paper presents a method that detects the MPM in the thoracic cavity and plans the photodynamic therapy in the preoperative phase. This is achieved by using a texture analysis of the MPM region combined with a thoracic cavity segmentation method. The algorithm to segment the thoracic cavity consists of multiple stages. First, the rib cage structure is segmented using various image processing techniques. We used the segmented rib cage to detect feature points which represent the thoracic cavity boundaries. Next, the proposed method segments the structures of the inner thoracic cage and fits 2D closed curves to the detected pleural cavity features in each slice. The missing bone structures are interpolated using a prior knowledge from manual segmentation performed by an expert. Next, the tumor region is segmented inside the thoracic cavity using a texture analysis approach. Finally, the contact surface between the tumor region and the thoracic cavity curves is reconstructed in order to plan the photodynamic therapy. Using the adjusted output of the thoracic cavity segmentation method and the MPM segmentation method, we evaluated the contact surface generated from these two steps by comparing it to the ground truth. For this evaluation, we used 10 CT scans with pathologically confirmed MPM at stages 1 and 2. We obtained a high similarity rate between the manually planned surface and our proposed method. The average value of Jaccard index

  10. Serratia marcescens resistance profile and its susceptibility to photodynamic antimicrobial chemotherapy.

    Science.gov (United States)

    Parente, Ticiana Mont Alverne Lopes; Rebouças, Emanuela de Lima; Santos, Vitor Coutinho Vieira Dos; Barbosa, Francisco Cesar Barroso; Zanin, Iriana Carla Junqueira

    2016-06-01

    Some authors have reported the antimicrobial action of photodynamic antimicrobial chemotherapy (PACT) on bacteria related to nosocomial infections but there are few studies evaluating PACT on Serratia marcescens grown as planktonic cultures or as biofilms. The purpose of this study was to analyze the S. marcescens resistance profile and its susceptibility to PACT. Initially, 55 S. marcescens strains isolated from environmental, oral and extra-oral infections were tested by antimicrobial resistance to cefotaxime (CTX), imipenem (IPM), ciprofloxacin (CIP), tobramycin (TOB) and doxycycline (DOX) using E-test(®). Following, isolates grown as planktonic cultures or biofilms were submitted to PACT using the association of a light-emitting diode and toluidine blue (TBO). The E-test(®) results demonstrated intermediated sensitive strains to CTX, IMP, TOB, and DOX; and resistant strains to CTX, TOB, DOX and CIP. Also, CTX and IMP demonstrated variation when CLSI 2007 and CLSI 2015 were compared. Planktonic cultures and biofilms submitted to PACT demonstrated counts varying from 10(11) to 10(7) for planktonic cultures and 10(10) to 10(7) for biofilms. There were no statistical differences in the results when planktonic cultures and biofilms were compared. Increase in the profile of S. marcescens resistance was observed when CLSI 2007 and CLSI 2015 were compared. Also, IMP remains as the drug with lower rate of resistance. Additionally, both S. marcescens planktonic cultures and early biofilms are susceptible to PACT under tested conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Stimulation of human gingival fibroblasts viability and growth by roots treated with high intensity lasers, photodynamic therapy and citric acid.

    Science.gov (United States)

    Karam, Paula Stephania Brandão Hage; Ferreira, Rafael; Oliveira, Rodrigo Cardoso; Greghi, Sebastião Luiz Aguiar; de Rezende, Maria Lúcia Rubo; Sant'Ana, Adriana Campos Passanezi; Zangrando, Mariana Schutzer Ragghianti; Damante, Carla Andreotti

    2017-09-01

    The aim of this study was to compare the effect of root biomodification by lasers, citric acid and antimicrobial photodynamic therapy (aPDT) on viability and proliferation of human gingival fibroblasts (FGH). Groups were divided in control (CC - only cells), and root fragments treated by: scaling and root planing (positice control - SC), Er:YAG (ER-60mJ,10pps,10Hz,10s,2940nm), Nd:YAG (ND-0.5W,15Hz,10s,1640nm), antimicrobial photodynamic therapy (PDT-InGaAIP,30mW,45J/cm 2 ,30s,660nm,toluidine blue O), citric acid plus tetracycline (CA). Fibroblasts (6th passage, 2×10 3 ) were cultivated in a 24-h conditioned medium by the treated root fragments. Cell viability was measured by MTT test at 24, 48, 72 and 96h. In a second experiment, FGH cells (10 4 ) were cultivated on root fragments which received the same treatments. After 24, 48, 72h the number of cells was counted in SEM pictures. In addition, chemical elements were analyzed by energy dispersive spectroscopy (EDS). Data was analyzed by two-way ANOVA (first experiment), repeated measures ANOVA (second experiment) and ANOVA (EDS experiment) tests complemented by Tukey's test (pplaning stimulated fibroblast viability while Er:YAG and Nd:YAG treated root surfaces presented higher number of cells. Copyright © 2017. Published by Elsevier Ltd.

  12. Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo.

    Science.gov (United States)

    de Freitas, Laura Marise; Calixto, Giovana Maria Fioramonti; Chorilli, Marlus; Giusti, Juçaíra Stella M; Bagnato, Vanderlei Salvador; Soukos, Nikolaos S; Amiji, Mansoor M; Fontana, Carla Raquel

    2016-05-20

    Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT-in planktonic and biofilm phases-with MB or MB-NP (25 µg/mL) at 20 J/cm² in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm²) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.

  13. Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo

    Directory of Open Access Journals (Sweden)

    Laura Marise de Freitas

    2016-05-01

    Full Text Available Antimicrobial photodynamic therapy (aPDT is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB-loaded poly(lactic-co-glycolic (PLGA nanoparticles (MB-NP and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 µg/mL at 20 J/cm2 in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm2 in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82% on gingival bleeding index (GBI compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.

  14. Antimicrobial photodynamic activity and cytocompatibility of Au25(Capt18 clusters photoexcited by blue LED light irradiation

    Directory of Open Access Journals (Sweden)

    Miyata S

    2017-04-01

    Full Text Available Saori Miyata,1 Hirofumi Miyaji,1 Hideya Kawasaki,2 Masaki Yamamoto,2 Erika Nishida,1 Hiroko Takita,3 Tsukasa Akasaka,4 Natsumi Ushijima,3 Toshihiko Iwanaga,5 Tsutomu Sugaya1 1Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo, 2Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita-shi, Osaka, 3Support Section for Education and Research, Hokkaido University Graduate School of Dental Medicine, 4Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, 5Department of Anatomy, Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan Abstract: Antimicrobial photodynamic therapy (aPDT has beneficial effects in dental treatment. We applied captopril-protected gold (Au25(Capt18 clusters as a novel photosensitizer for aPDT. Photoexcited Au clusters under light irradiation generated singlet oxygen (1O2. Accordingly, the antimicrobial and cytotoxic effects of Au25(Capt18 clusters under dental blue light-emitting diode (LED irradiation were evaluated. 1O2 generation of Au25(Capt18 clusters under blue LED irradiation (420–460 nm was detected by a methotrexate (MTX probe. The antimicrobial effects of photoexcited Au clusters (0, 5, 50, and 500 µg/mL on oral bacterial cells, such as Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, were assessed by morphological observations and bacterial growth experiments. Cytotoxicity testing of Au clusters and blue LED irradiation was then performed against NIH3T3 and MC3T3-E1 cells. In addition, the biological performance of Au clusters (500 µg/mL was compared to an organic dye photosensitizer, methylene blue (MB; 10 and 100 µg/mL. We confirmed the 1O2 generation ability of Au25(Capt18 clusters through the fluorescence

  15. Modeling the oxygen microheterogeneity of tumors for photodynamic therapy dosimetry

    Science.gov (United States)

    Pogue, Brian W.; Paulsen, Keith D.; O'Hara, Julia A.; Hoopes, P. Jack; Swartz, Harold

    2000-03-01

    Photodynamic theory of tumors uses optical excitation of a sensitizing drug within tissue to produce large deposits of singlet oxygen, which are thought to ultimately cause the tumor destruction. Predicting dose deposition of singlet oxygen in vivo is challenging because measurement of this species in vivo is not easily achieved. But it is possible to follow the concentration of oxygen in vivo, and so measuring the oxygen concentration transients during PDT may provide a viable method of estimating the delivered dose of singlet oxygen. However modeling the microscopic heterogeneity of the oxygen distribution within a tumor is non-trivial, and predicting the microscopic dose deposition requires further study, but this study present the framework and initial calibration needed or modeling oxygen transport in complex geometries. Computational modeling with finite elements provides a versatile structure within which oxygen diffusion and consumption can be modeled within realistic tissue geometries. This study develops the basic tools required to simulate a tumor region, and examines the role of (i) oxygen supply and consumption rates, (ii) inter- capillary spacing, (iii) photosensitizer distribution, and (iv) differences between simulated tumors and those derived directly from histology. The result of these calculations indicate that realistic tumor tissue capillary networks can be simulated using the finite element method, without excessive computational burden for 2D regions near 1 mm2, and 3D regions near 0.1mm3. These simulations can provide fundamental information about tissue and ways to implement appropriate oxygen measurements. These calculations suggest that photodynamic therapy produces the majority of singlet oxygen in and near the blood vessels, because these are the sites of highest oxygen tension. These calculations support the concept that tumor vascular regions are the major targets for PDT dose deposition.

  16. Evaluation of the Effects of Photodynamic Therapy Alone and Combined with Standard Antifungal Therapy on Planktonic Cells and Biofilms of Fusarium spp. and Exophiala spp.

    Science.gov (United States)

    Gao, Lujuan; Jiang, Shaojie; Sun, Yi; Deng, Meiqi; Wu, Qingzhi; Li, Ming; Zeng, Tongxiang

    2016-01-01

    Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 μg/ml) as a photosensitizing agent and light emitting diode (635 ± 10 nm, 12 and 24 J/cm(2)), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of ≥16, 4-8, 4-8, and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in

  17. Photodynamic therapy platform for glioblastoma and intrabronchial tumors

    Science.gov (United States)

    Orsila, Lasse; Alanko, Jukka-Pekka; Kaivosoja, Visa; Uibu, Toomas

    2018-02-01

    Photodynamic therapy (PDT) is bringing new, effective, and less invasive, possibilities for cancer treatment. ML7710 (Modulight Inc.) medical laser system offers a platform for performing PDT for multiple indications and drugs. Latest avenue is glioblastoma treatment with 5-Aminolevulinic acid (ALA-5) and 635-nm light, where clinical trials are about to begin. Preliminary work suggests major advantages in treatment control, including active in-situ feedback. ML7710 platform has already proven itself for clinical work with intrabronchial obstructive tumors. Preliminary result with 10 patients show that intrabronchial tumors, that strongly affect both the survival and the performance of the patient, can be significantly reduced with ML7710 operated at 665 nm and sodium chlorine E6 photosensitizer. The aim in most of the patients has been a palliative recanalization of the bronchial lumen in order to alleviate the symptoms such as breathlessness and hemoptysis. The illumination dose for the target area was 50-75 J/cm2. All the patients have received multimodality cancer treatment using other intrabronchial interventions, radiotherapy and chemotherapy as needed. In most of the patients, satisfactory treatment results were achieved and it was possible to restart chemotherapy in several patients. In one patient with local cancer a complete remission was established. PDT has also the advantage that it is possible to give PDT after a maximum dose of radiation therapy has already been used and fewer side effects if used in locally advanced intraluminar lung cancer.

  18. Early and Late Onset Side Effects of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Borgia

    2018-01-01

    Full Text Available Photodynamic Therapy (PDT is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.

  19. Cell Death Pathways in Photodynamic Therapy of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mroz, Pawel, E-mail: pmroz@partners.org [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Yaroslavsky, Anastasia [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Boston University College of Engineering, Boston, MA 02114 (United States); Kharkwal, Gitika B [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Hamblin, Michael R. [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139 (United States)

    2011-06-03

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.

  20. Verteporfin: a milestone in opthalmology and photodynamic therapy.

    Science.gov (United States)

    Brown, S B; Mellish, K J

    2001-02-01

    During the past year, a photosensitiser named benzoporphyrin derivative (BPD) has been approved in 26 countries under the generic name verteporfin (Visudynetrade mark, Novartis), for the treatment of patients with a certain type of the wet form of age-related macular degeneration (AMD) by photodynamic therapy (PDT). AMD is the leading cause of blindness in the developed world, with approximately half a million new cases of the wet form per year. The approval of Visudynetrade mark therapy represents a major milestone in ophthalmology since AMD was previously untreatable by any modality which would preserve existing vision. It was also a milestone in the development of PDT, not only because it represented the first breakthrough in the use of PDT to treat an otherwise untreatable condition, but also because it represented the first mass market for a PDT treatment where prospects of a substantial financial return on many years of investment appear to be likely. In this article, we look at the background to the development of BPD, primarily for its use in AMD, but also in other applications.

  1. Cell Death Pathways in Photodynamic Therapy of Cancer

    International Nuclear Information System (INIS)

    Mroz, Pawel; Yaroslavsky, Anastasia; Kharkwal, Gitika B; Hamblin, Michael R.

    2011-01-01

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT

  2. Photodynamic therapy in early esophageal squamous cell carcinoma

    Science.gov (United States)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

    1995-03-01

    From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

  3. Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivative for bacterial skin infection

    Science.gov (United States)

    Chen, Zhuo; Zhang, Yaxin; Li, Linsen; Zhou, Shanyong; Chen, Jincan; Hu, Ping; Huang, Mingdong

    2014-09-01

    Folliculitis, furunculosis and acne vulgaris are very common skin disorders of the hair follicles and are associated with large grease-producing (sebaceous) glands. Although the detailed mechanisms involved these skin disorders are not fully understood, it is believed that the bacteria Propionibacterium acnes and Staphylococcus aureus are the key pathogenic factors involved. Conventional treatments targeting the pathogenic factors include a variety of topical and oral medications such as antibiotics. The wide use of antibiotics leads to bacterial resistance, and hence there is a need for new alternatives in above bacterial skin treatment. Photodynamic antimicrobial chemotherapy (PACT) is based on an initial photosensitization of the infected area, followed by irradiation with visible light, producing singlet oxygen which is cytotoxic to bacteria. Herein we reported a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5) and its PACT effect for the bacteria involved in these skin infections. Our results demonstrated strong bactericidal effects of this photosensitizer on both strains of the bacteria, suggesting ZnPc-(Lys)5 as a promising antimicrobial photosensitizer for the treatment of infectious diseases caused by these bacteria.

  4. Effective photodynamic therapy against microbial populations in human deep tissue abscess aspirates.

    Science.gov (United States)

    Haidaris, Constantine G; Foster, Thomas H; Waldman, David L; Mathes, Edward J; McNamara, Joanne; Curran, Timothy

    2013-10-01

    The primary therapy for deep tissue abscesses is drainage accompanied by systemic antimicrobial treatment. However, the long antibiotic course required increases the probability of acquired resistance, and the high incidence of polymicrobial infections in abscesses complicates treatment choices. Photodynamic therapy (PDT) is effective against multiple classes of organisms, including those displaying drug resistance, and may serve as a useful adjunct to the standard of care by reduction of abscess microbial burden following drainage. Aspirates were obtained from 32 patients who underwent image-guided percutaneous drainage of the abscess cavity. The majority of the specimens (24/32) were abdominal, with the remainder from liver and lung. Conventional microbiological techniques and nucleotide sequence analysis of rRNA gene fragments were used to characterize microbial populations from abscess aspirates. We evaluated the sensitivity of microorganisms to methylene blue-sensitized PDT in vitro both within the context of an abscess aspirate and as individual isolates. Most isolates were bacterial, with the fungus Candida tropicalis also isolated from two specimens. We examined the sensitivity of these microorganisms to methylene blue-PDT. Complete elimination of culturable microorganisms was achieved in three different aspirates, and significant killing (P abscess treatment. © 2013 Wiley Periodicals, Inc.

  5. Photodynamic therapy to destroy pneumonia associated microorganisms using external irradiation source

    Science.gov (United States)

    Bassi, Rosane; Myakawa, Walter; Navarro, Ricardo S.; Baptista, Alessandra; Ribeiro, Martha Simões; Nunez, Silvia Cristina

    2018-02-01

    An endotracheal tube (ETT) is required for the management of critically ill, mechanically ventilated patients. Ventilatorassociated pneumonia (VAP) affects patients hospitalized in intensive care units; its risk of occurrence is 1% to up 3% for each day of mechanical ventilation. The polymicrobial nature of VAP is established with mixed bacterial-fungal biofilms colonizing the ETT. The microbial interaction enhances the microbial pathogenesis contributing to high indexes of morbidity/mortality. Antimicrobial Photodynamic Therapy (aPDT) could be a suitable therapy for decontamination of oral cavity and ETT at the same time, but the use of a fiber optics inside the ETT seems to not be appropriated since a cannula for secretion aspiration has to be introduced into the ETT to keep it's lumen. The aim of this study is to proof the concept that an external light source from a LED is capable of reach all areas of the ETT. We use a commercial ETT, 60μM methylene blue (MB), and a 660nm diode laser and calculated the transmission coefficient of light in different situations as only tube, tube with biofilm and biofilm+MB. The results prove that is possible to transmit light through the tube even in the presence of MB and biofilm although a high attenuation of about 60% was measured depending on the tested condition.

  6. Histological responses of cutaneous vascular lesions following photodynamic therapy with talaporfin sodium: a chicken comb model.

    Science.gov (United States)

    Ohshiro, Takafumi; Nakajima, Tatsuo; Ogata, Hisao; Kishi, Kazuo

    2009-09-01

    Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and is currently being used in photodynamic therapy for various malignant tumors in combination with irradiation with a 664 nm laser. An interesting characteristic of Talaporfin sodium is that the skin photosensitivity after injection of this agent disappears faster than any other existing photosensitizers. This study examined the vascular events that occurred postirradiation in the chicken comb as a capillary malformation model after photosensitization with Talaporfin sodium. A single intravenous bolus injections of Talaporfin sodium was administered to the chickens, and a 1 cm diameter area of the comb of each animal was irradiated with a 664 nm visible red laser. The gross changes in the chicken combs were recorded for 7-14 days after photodynamic therapy. For the histological examination, HE, PTAH and Azan stained sections were analyzed. All treated chicken combs had blanched after photodynamic therapy. Microscopy demonstrated an absence of erythrocytes and the vessel lumina were obliterated, leaving the normal overlying epidermis completely intact. Concomitantly with selective destruction of the capillaries in the target area, moderate invasion of inflammatory cells and a slight increase in the stroma were observed. In the chicken comb model, photodynamic therapy with Talaporfin sodium effectively achieved selective destruction of the microvasculature while leaving the epidermis intact. Our results strongly suggest that photodynamic therapy with Talaporfin sodium could be a feasible method to treat dermal hypervascular lesions.

  7. Photodynamic antimicrobial chemotherapy (PACT for the treatment of malaria, leishmaniasis and trypanosomiasis

    Directory of Open Access Journals (Sweden)

    M.S. Baptista

    2011-01-01

    Full Text Available A photodynamic effect occurs when photosensitiser molecules absorb light and dissipate the absorbed energy by transferring it to biological acceptors (usually oxygen, generating an excess of reactive species that are able to force cells into death pathways. Several tropical diseases present physiopathological aspects that are accessible to the application of a photosensitiser and local illumination. In addition, disease may be transmitted through infected blood donations, and many of the aetiological agents associated with tropical diseases have been shown to be susceptible to the photodynamic approach. However, there has been no systematic investigation of the application of photoantimicrobial agents in the various presentations, whether to human disease or to the disinfection of blood products or even as photo-insecticides. We aim in this review to report the advances in the photoantimicrobial approach that are beneficial to the field of anti-parasite therapy and also have the potential to facilitate the development of low-cost/high-efficiency protocols for underserved populations.

  8. The effect of laser unit on photodynamic therapy spot size.

    Science.gov (United States)

    Ansari-Shahrezaei, Siamak; Binder, Susanne; Stur, Michael

    2011-01-01

    To determine the effect of the laser unit on photodynamic therapy (PDT) spot size. A calibrated Gullstrand-type model eye was used for this study. The axial length of the model eye was set to different values ranging from 22.2 to 27.0 mm, and the actual spot size from the laser console was recorded for treating a spot of 4 mm in the center of the artificial fundus using two different laser units (Coherent Opal laser; Coherent Inc, Santa Clara, California, USA and Zeiss Visulas laser; Carl Zeiss Meditec Inc, Dublin, California, USA) and two indirect contact laser lenses (Volk PDT laser lens and Volk Area Centralis lens; Volk Optical Inc, Mentor, Ohio, USA). From myopia to hyperopia, the total deviation from the intended spot size was -22.5% to -7.5% (Opal laser and PDT laser lens), and -17.5% to +2.5% (Visulas laser and PDT laser lens), -12.5% to +7.5% (Opal laser and Area Centralis lens), and -7.5% to +10% (Visulas laser and Area Centralis lens). The used laser unit has a significant effect on PDT spot size in this model. These findings may be important for optimizing PDT of choroidal neovascular lesions.

  9. Extended rhodamine photosensitizers for photodynamic therapy of cancer cells.

    Science.gov (United States)

    Davies, Kellie S; Linder, Michelle K; Kryman, Mark W; Detty, Michael R

    2016-09-01

    Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M). Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Treatment of oral leukoplakia with photodynamic therapy: A pilot study

    Directory of Open Access Journals (Sweden)

    Niranzena Panneer Selvam

    2015-01-01

    Full Text Available Aim of the Study: Oral leukoplakia (OL is the most common potentially malignant disorder that may transform into oral carcinoma. By treating leukoplakia in its incipient stage, the risk of occurrence of oral carcinoma can be prevented. In this aspect, photodynamic therapy (PDT can serve as a useful treatment modality. The aim of the study is to treat patients with OL using PDT in which 5-aminolevulinic acid (ALA is used as a photosensitizer. Materials and Methods: Five patients with OL were included in the study. They were treated with 10% ALA mediated PDT (light source: Xenon lamp, power: 0.1 W, wavelength: 630 ± 5 nm, total dose: 100 J/cm 2 per session for 6-8 sessions. Follow-up was done for a period of 1 year. Results: One month (4 weeks after ALA-PDT, the response was evaluated based on clinical examination. It was as follows: Complete response: Two patients; partial response: Two patients; and no response: One patient. There was no recurrence in any of the cases. Conclusion: There was satisfactory reduction in the size of the OL lesion without any side-effects. Thus, ALA mediated PDT seems to be a promising alternative for the treatment of OL.

  11. Development and optimization of a diode laser for photodynamic therapy.

    Science.gov (United States)

    Lim, Hyun Soo

    2011-01-01

    This study demonstrated the development of a laser system for cancer treatment with photodynamic therapy (PDT) based on a 635 nm laser diode. In order to optimize efficacy in PDT, the ideal laser system should deliver a homogeneous nondivergent light energy with a variable spot size and specific wavelength at a stable output power. We developed a digital laser beam controller using the constant current method to protect the laser diode resonator from the current spikes and other fluctuations, and electrical faults. To improve the PDT effects, the laser system should deliver stable laser energy in continuous wave (CW), burst mode and super burst mode, with variable irradiation times depending on the tumor type and condition. The experimental results showed the diode laser system described herein was eminently suitable for PDT. The laser beam was homogeneous without diverging and the output power increased stably and in a linear manner from 10 mW to 1500 mW according to the increasing input current. Variation between the set and delivered output was less than 7%. The diode laser system developed by the author for use in PDT was compact, user-friendly, and delivered a stable and easily adjustable output power at a specific wavelength and user-set emission modes.

  12. Molecular photosensitisers for two-photon photodynamic therapy.

    Science.gov (United States)

    Bolze, F; Jenni, S; Sour, A; Heitz, V

    2017-11-30

    Two-photon excitation has attracted the attention of biologists, especially after the development of two-photon excited microscopy in the nineties. Since then, new applications have rapidly emerged such as the release of biologically active molecules and photodynamic therapy (PDT) using two-photon excitation. PDT, which requires a light-activated drug (photosensitiser), is a clinically approved and minimally invasive treatment for cancer and for non-malignant diseases. This feature article focuses on the engineering of molecular two-photon photosensitisers for PDT, which should bring important benefits to the treatment, increase the treatment penetration depth with near-infrared light excitation, improve the spatial selectivity and reduce the photodamage to healthy tissues. After an overview of the two-photon absorption phenomenon and the methods to evaluate two-photon induced phototoxicity on cell cultures, the different classes of photosensitisers described in the literature are discussed. The two-photon PDT performed with historical one-photon sensitisers are briefly presented, followed by specifically engineered cyclic tetrapyrrole photosensitisers, purely organic photosensitisers and transition metal complexes. Finally, targeted two-photon photosensitisers and theranostic agents that should enhance the selectivity and efficiency of the treatment are discussed.

  13. Photodynamic therapy and diagnosis: Principles and comparative aspects.

    Science.gov (United States)

    Dobson, Jane; de Queiroz, Genilson Fernandes; Golding, Jon P

    2018-03-01

    Photodynamic therapy (PDT) is an evolving method of treating superficial tumours that is non-invasive and carries minimal risk of toxicity. It combines tumour-selective photosensitiser dyes, tissue oxygen and targeted illumination to generate cytotoxic reactive oxygen species (ROS) within the tumour. In addition to directly acting on tumour cells, PDT damages and restricts tumour microvasculature, and causes a local inflammatory response that stimulates an immune response against the tumour. Unlike surgery or radiotherapy, the surrounding extracellular matrix is unaffected by PDT; thus, tissue healing is excellent and PDT seldom causes scars. This, combined with the ease of light application, has made PDT a popular treatment for cancers and pre-cancerous conditions in human beings. Moreover, because photosensitiser dyes are fluorescent and selectively accumulate in tumour tissues, they can additionally be used to visualise and discriminate tumour from normal tissues, thereby improving the accuracy of tumour surgery. In veterinary practice, PDT has been used successfully for treatment of superficial squamous cell carcinomas of the feline nasal planum; urinary tract, urinary bladder and prostate neoplasia in dogs; and equine sarcoids. The purpose of this article is to provide a comparative review of the current literature on PDT in human and veterinary medicine, and to establish a basis for future development of PDT in veterinary medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Usefulness of Photodynamic Therapy in the Management of Onychomycosis.

    Science.gov (United States)

    Robres, P; Aspiroz, C; Rezusta, A; Gilaberte, Y

    2015-12-01

    Onychomycosis, or fungal infection of the nails, is one of the most prevalent fungal diseases in the general population. Treatment is of limited effectiveness, tedious, and must be administered for long periods. Furthermore, systemic antifungal agents are associated with adverse effects. Photodynamic therapy (PDT) may prove to be a viable alternative in the treatment of superficial skin infections, including onychomycosis. We review articles relating to the usefulness of PDT in onychomycosis in both in vitro and in vivo settings and discuss the potential and limitations of various photosensitizing agents. In vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and 43% of cases, respectively, at 12 months. Finally, based on data in the literature and our own experience, we propose a protocol of 3 PDT sessions, separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a photosensitizing agent and red light (λ=630 nm, 37 J.cm(-2)). Each session is preceded by the topical application of urea 40% over several days. Clinical trials are needed to optimize PDT protocols and to identify those patients who will benefit most from this treatment. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  15. Four-year clinical experience in photodynamic therapy

    Science.gov (United States)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.; Vorozhtsov, Georgy N.; Mironov, Andrei F.; Markichev, Nikolai A.; Riabov, Michail V.

    1996-12-01

    The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of skin, breasts, tongue, oral mucose, lower lip, larynx, stomach, bladder, rectum and other locations has been made. During 1992 - 1996 867 tumoral foci in 222 patients have been treated with PDT. All patients were previously treated with conventional techniques or they were not treated due to contraindications either because of severe accompanying diseases or because of old age. A part of the patients had PDT because of recurrences or intradermal metastases in 1 - 2 years after surgical, radial or combined treatment. Up to now we have follow-up control data within 2 months and 4 years. Positive effect of PDT was seen in 93.7% of patients including complete regression of tumors in 64.9% and partial in 28.8%. Currently this new perspective technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.

  16. Predictive analysis of photodynamic therapy applied to esophagus cancer

    Science.gov (United States)

    Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2008-04-01

    The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

  17. [Current status and prospect of photodynamic therapy in laryngeal diseases].

    Science.gov (United States)

    Zhang, C; Jiang, J Q

    2018-04-07

    Laryngeal diseases are closely related to the swallowing and speech function of the patients.Protecting and restoring laryngeal function, while curing lesions, is vital to patients' quality of life.Photodynamic therapy (PDT) is a minimally invasive method which is widely used in the treatment of tumor, precancerous lesions, and inflammatory diseases.In recent years, it has been shown to have a protective effect on normal structures. This article reviews the clinical outcomes of laryngeal diseases treated with PDT since 1990 in order to evaluate its efficacy and significance. The complete remission rate of early-stage laryngeal tumors and precancerous lesions after PDT is 77.6%(249/321), and a promising effect on recurrent laryngeal papillomatosis has been observed thus far. The prolonged adverse effects of the first-generation photosensitizers have limited the application of PDT. With the improvement of photosensitizers and treatment strategies, PDT promises to be a safe, effective, and minimally invasive treatment method for laryngeal diseases.

  18. Core - shell upconversion nanoparticle - semiconductor heterostructures for photodynamic therapy

    Science.gov (United States)

    Dou, Qing Qing; Rengaramchandran, Adith; Selvan, Subramanian Tamil; Paulmurugan, Ramasamy; Zhang, Yong

    2015-02-01

    Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980 nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ~45% cancer cell death as measured by MTT assay, when illuminated with 980 nm NIR light.

  19. Photodynamic therapy for melanoma: efficacy and immunologic effects

    Science.gov (United States)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  20. Daylight-mediated photodynamic therapy in Spain: advantages and disadvantages.

    Science.gov (United States)

    Pérez-Pérez, L; García-Gavín, J; Gilaberte, Y

    2014-09-01

    Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated patients. Copyright © 2013 Elsevier España, S.L.U. y AEDV. All rights reserved.

  1. Photodynamic Therapy and Non-Melanoma Skin Cancer

    Directory of Open Access Journals (Sweden)

    Liezel L. Griffin

    2016-10-01

    Full Text Available Non-melanoma skin cancer (NMSC is the most common malignancy among the Caucasian population. Photodynamic therapy (PDT is gaining popularity for the treatment of basal cell carcinoma (BCC, Bowen’s disease (BD and actinic keratosis (AK. A topical or systemic exogenous photosensitiser, results in selective uptake by malignant cells. Protoporphyrin IX (PpIX is produced then activated by the introduction of a light source. Daylight-mediated MAL (methyl aminolaevulinate PDT for AKs has the advantage of decreased pain and better patient tolerance. PDT is an effective treatment for superficial BCC, BD and both individual and field treatment of AKs. Excellent cosmesis can be achieved with high patient satisfaction. Variable results have been reported for nodular BCC, with improved outcomes following pretreatment and repeated PDT cycles. The more aggressive basisquamous, morphoeic infiltrating subtypes of BCC and invasive squamous cell carcinoma (SCC are not suitable for PDT. Prevention of “field cancerization” in organ transplant recipients on long-term immunosuppression and patients with Gorlin syndrome (naevoid basal cell carcinoma syndrome is a promising development. The optimisation of PDT techniques with improved photosensitiser delivery to target tissues, new generation photosensitisers and novel light sources may expand the future role of PDT in NMSC management.

  2. Subretinal Hemorrhage after Photodynamic Therapy for Juxtapapillary Retinal Capillary Hemangioma

    Directory of Open Access Journals (Sweden)

    Takayuki Baba

    2011-04-01

    Full Text Available A 75-year-old Japanese woman presented with a juxtapapillary retinal capillary hemangioma (RCH in her left eye. Twelve months after the initial examination, the size of the hemangioma had increased and the exudation from the RCH involved the macula. Her best-corrected visual acuity (BCVA had decreased from 0.8 to 0.3. A total of five intravitreal injections of bevacizumab (IVB; 1.25 mg was given but the RCH did not respond. A photodynamic therapy (PDT was done using multiple laser spots to avoid damaging the optic nerve head. After the first PDT, the subfoveal fluid was reduced but not completely gone. One week after the second PDT, a massive subretinal hemorrhage developed. The subretinal hemorrhage was successfully displaced by injecting intraocular sulfur hexafluoride (SF6 gas. At the 3-year follow-up examination, no subretinal hemorrhage or fluid was observed at the macula and the BCVA remained at 0.05. Our case was resistant to the combination of anti-vascular endothelial growth factor (VEGF and PDT and had a rare massive subretinal hemorrhage. A further collection of RCH cases treated with anti-VEGF and PDT that would justify this treatment is necessary.

  3. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    International Nuclear Information System (INIS)

    Wang, W; Moriyama, L T; Bagnato, V S

    2013-01-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed. (review)

  4. Evaluation of actual vs expected photodynamic therapy spot size.

    Science.gov (United States)

    Ranchod, Tushar M; Brucker, Alexander J; Liu, Chengcheng; Cukras, Catherine A; Hopkins, Tim B; Ying, Gui-Shuang

    2009-05-01

    To determine the accuracy of the photodynamic therapy (PDT) laser spot size on the retina as generated by 2 Food and Drug Administration (FDA)-approved lasers. Prospective observational case series. Fundus photographs were taken of 1 eye of each of 10 subjects with the WinStation 4000 fundus photography system (OIS; Ophthalmic Imaging Systems, Sacramento, California, USA); disc size was calculated using OIS software. Slit-lamp photographs were taken of the PDT laser spot focused on the retina adjacent to the optic disc, using various spot sizes in combination with 3 different contact lenses and 2 different lasers. Spot size at the retina was determined by measuring the ratio of disc diameter to spot diameter in Adobe Photoshop (San Jose, California, USA) and applying this ratio to the OIS disc measurements. Spot size at the retina averaged 87% of expected spot size for the Coherent Opal laser (Coherent Inc, Santa Clara, California, USA) and 104% of expected spot size for the Zeiss Visulas laser (Carl Zeiss Meditec Inc, Dublin, California, USA)(P = .002). Multivariate analysis demonstrated that percentage of expected spot size decreased with larger spot diameter (P = .01 for Coherent laser; P = .02 for Zeiss laser). PDT spot size at the retina appears to be consistently smaller than expected for the Coherent laser while the spot size was consistently within 10% of expected size for the Zeiss laser. The deviation from expected size increased with larger spot size using the Coherent laser.

  5. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    Science.gov (United States)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  6. Trifluoromethyl Boron Dipyrromethene Derivatives as Potential Photosensitizers for Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Jian-Yong Liu

    2018-02-01

    Full Text Available In this study, two novel boron dipyrromethene-based photosensitizers (BDP3 and BDP6 substituted with three or six trifluoromethyl groups have been synthesized and characterized with various spectroscopic methods, and their photo-physical, photo-chemical, and photo-biological properties have also been explored. The two photosensitizers are highly soluble and remain nonaggregated in N,N-dimethylformamide as shown by the intense and sharp Q-band absorption. Under red light irradiation (λ = 660 nm, 1.5 J/cm2, both photosensitizers show high and comparable cytotoxicity towards HepG2 human hepatocarcinoma and HeLa human cervical carcinoma cells with IC50 values of 0.42–0.49 μM. The high photocytotoxicity of BDP3 and BDP6 can be due to their high cellular uptake and low aggregation tendency in biological media, which result in a high efficiency to generate reactive oxygen species inside the cells. Confocal laser fluorescence microscopic studies indicate that they have superior selective affinities to the mitochondria and lysosomes of HepG2 and HeLa cells. The results show that these two trifluoromethyl boron dipyrromethene derivatives are potential anticancer agents for photodynamic therapy.

  7. Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

    Science.gov (United States)

    Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

    2015-01-01

    A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

  8. Development of Smart Phthalocyanine-based Photosensitizers for Photodynamic Therapy

    Science.gov (United States)

    Chow, Yun Sang

    Phthalocyanines are versatile functional dyes that have shown great potential in cancer theranostics, especially in photodynamic therapy (PDT). This research work aims to develop "smart" phthalocyanine-based photosensitizers for targeted PDT. This thesis describes the synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities of several series of carefully designed phthalocyanine-based photosensitizers. Chapter 1 presents an overview of PDT, including its historical development, photophysical mechanisms, and biological mechanisms. Various classes of photosensitizers are introduced with emphasis putting on phthalocyanines, which exhibit ideal characteristics of photosensitizers for PDT. In recent years, several approaches have been used to develop photosensitizers with higher tumor selectivity and minimal skin photosensitivity after PDT. Activatable photosensitizers can provide a "turn on" mechanism to offer an additional control of the specificity of treatment. Photosensitizers can also work cooperatively with the tumor-targeting groups or anticancer drugs so as to achieve targeted or dual therapy, which can enhance the efficacy of PDT. The novel approaches mentioned above have been widely used and combined to form multi-functional photosensitizing agents. These novel concepts and development of PDT are discussed and illustrated with relevant examples at the end of this chapter. To minimize the prolonged skin photosensitivity, photosensitizers that can only be activated by tumor-associated stimuli have been developed. Due to the abnormal metabolism in tumor tissues, their surface usually exhibits a lower pH compared to that of the normal tissues. Also, the pH difference between the intracellular and the physiological environment provides a pH-activation mechanism. Chapter 2 presents the synthesis and spectroscopic characterization of a pH-responsive zinc(II) phthalocyanine tetramer, in which the phthalocyanine units

  9. Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy

    International Nuclear Information System (INIS)

    Korbelik, M.; Sun, J.

    2003-01-01

    Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy x-ray dose). PDT-vaccine treatment, done by peritumoral injection of in vitro PDT-treated SCCVII cells (20 million/mouse), was performed either immediately after radiotherapy or ten days later. The mice were then observed for tumor regression/recurrence. The tumors treated with radiotherapy alone shrunk and became impalpable for a brief period after which they all recurred. In contrast, vaccination performed at 10 days post radiotherapy delayed tumor recurrence and prevented it in one of six mice. Even better results were obtained with mice vaccinated immediately after radiotherapy, with mice showing not only a delayed tumor recurrence but also no sign of tumor in 50% of mice. The PDT-vaccine treatment without radiotherapy produced in this trial a significant tumor growth retardation but no complete regressions. These results indicate that PDT-generated vaccines can ensure immune rejection of cancer once the lesion size is reduced by radiotherapy. Even without obtaining a systemic immunity for the elimination of disseminated malignant deposits, these findings suggest that PDT-vaccines can improve local control

  10. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  11. Performance of a light applicator for photodynamic therapy in the oral cavity: calculations and measurements

    NARCIS (Netherlands)

    van Benthem, H. E.; Sterenborg, H. J.; van der Meulen, F. W.; van Gemert, M. J.

    1997-01-01

    Photodynamic therapy (PDT) is an experimental therapy for the treatment of superficial cancer using laser light. In PDT a uniform light distribution is usually required for an optimal therapeutic effect. To irradiate part of the oral cavity uniformly for PDT, two prototype applicators were built,

  12. Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis

    DEFF Research Database (Denmark)

    Morton, C A; Wulf, H C; Szeimies, R M

    2015-01-01

    INTRODUCTION: Daylight-mediated photodynamic therapy has been shown to be an effective therapy for actinic keratoses (AKs) and a simple and tolerable treatment procedure in three randomized Scandinavian studies and two recent Phase III randomized controlled studies in Australia and Europe...

  13. Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy

    DEFF Research Database (Denmark)

    Togsverd-Bo, K; Omland, S H; Wulf, H C

    2015-01-01

    Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK...

  14. Switching From Conventional Photodynamic Therapy to Daylight Photodynamic Therapy For Actinic Keratoses: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Tomás-Velázquez, A; Redondo, P

    2017-05-01

    Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the procedure is time-consuming, can be very painful, and requires infrastructure. These shortcomings led to the emergence of daylight PDT. To obtain a global estimate of efficacy, we undertook a systematic literature review and performed a meta-analysis of the available evidence on the efficacy and safety of daylight PDT as compared to conventional PDT in the treatment of actinic keratosis and/or field cancerization. The conclusion is that the difference in efficacy is clinically negligible (global estimate of the mean response rate difference, -3.69%; 95% CI, -6.54% to -0.84%). The adverse effects of daylight PDT are mild and localized (79% of patients report no discomfort), and patients report less pain (P<.001). Daylight PDT gives good to excellent cosmetic results in more than 90% of patients, and patient satisfaction is greater (P<.001). Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy.

    Science.gov (United States)

    Hammerer, Fabien; Poyer, Florent; Fourmois, Laura; Chen, Su; Garcia, Guillaume; Teulade-Fichou, Marie-Paule; Maillard, Philippe; Mahuteau-Betzer, Florence

    2018-01-01

    The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Treatment of Oral Candidiasis Using Photodithazine®- Mediated Photodynamic Therapy In Vivo.

    Science.gov (United States)

    Carmello, Juliana Cabrini; Alves, Fernanda; G Basso, Fernanda; de Souza Costa, Carlos Alberto; Bagnato, Vanderlei Salvador; Mima, Ewerton Garcia de Oliveira; Pavarina, Ana Cláudia

    2016-01-01

    This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT) in the treatment of oral candidiasis in a murine model using Photodithazine® (PDZ). This model of oral candidiasis was developed to allow the monitoring of the infection and the establishment of the aPDT treatment. Six-week-old female mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDZ-mediated aPDT and nystatin treatment were carried out for 5 consecutive days with one application per day. The macroscopic evaluation of oral lesions was performed. After each treatment, the tongue was swabbed to recover C. albicans cells. Viable colonies were quantified and the number of CFU/ml determined. The animals were sacrificed 24 hours and 7 days after treatment and the tongues were surgically removed for histological analysis and analysis of inflammatory cytokines expression (IL-1, TNF-α and IL-6) by RT-qPCR. Data were analyzed by two-way ANOVA. PDZ-mediated aPDT was as effective as Nystatin (NYS group) in the inactivation of C. albicans, reducing 3 and 3.2 logs10 respectively, 24 h after treatment (poral lesions, while animals treated with NYS presented partial remission of oral lesions in both periods assessed. Histological evaluation revealed mild inflammatory infiltrate in the groups treated with aPDT and NYS in both periods assessed. The aPDT induced the TNF-α expression when compared with the control (P-L-) (poral candidiasis.

  17. Targeted photodynamic therapy of established soft-tissue infections in mice

    Science.gov (United States)

    Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

    2004-06-01

    The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to resistant soft-tissue infections.

  18. Evaluation of the dentin changes in teeth subjected to endodontic treatment and photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Mariane Floriano Lopes Santos LACERDA

    Full Text Available Abstract Introduction Antimicrobial photodynamic therapy (PDT is an efficient adjuvant technique to promote disinfection of the root canal system. Therefore, it is important to investigate changes to dentin morphology and permeability induced by the use of diode laser on the root dentin. Objective The purpose of this study was to investigate morphological changes and the percentage of apical leakage after the use of laser. Material and method Forty single-rooted teeth were instrumented using rotary system and irrigated. Teeth were randomly divided in two groups: G1 - not exposed to PDT (control, and G2 - pretreated with toluidine blue photosensitizer and irradiated with AsGaAl laser diode. Ten teeth in each group were evaluated by SEM for morphological changes. The other ten teeth were filled and stained with Rhodamine B to evaluate the apical leakage. Result The results showed significant difference between G1 and G2 (p 0.001. The apical leakage was significantly higher in G2 than in G1 (p <0.001 - Student's t-test. Conclusion It was concluded that the use of low-level laser reduced the smear layer and opened the dentinal tubules. Use of laser increased the permeability of the apical dentin.

  19. Potassium iodide potentiates antimicrobial photodynamic inactivation mediated by Rose Bengal: in vitro and in vivo studies

    Science.gov (United States)

    Wen, Xiang; Zhang, Xiaoshen; Szewczyk, Grzegorz; ElHussien, Ahmed; Huang, Ying-Ying; Sarna, Tadeusz; Hamblin, Michael R.

    2018-02-01

    Rose Bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation. While highly active against Gram-positive bacteria, RB is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the non-toxic salt potassium iodide (100mM) potentiates green light (540nm)-mediated killing by up to six extra logs with Gramnegative bacteria Escherichia coli and Pseudomonas aeruginosa,Gram-positive methicillin resistant Staphylococcus aureus, and fungal yeast Candida albicans. The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals, finally forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing killing in three different scenarios: (1) cells+RB+KI are mixed together then illuminated with green light; (2) cells+RB are centrifuged then KI added then green light; (3) RB+KI+green light then cells added after light. We showed that KI could potentiate RBPDT in a mouse model of skin abrasions infected with bioluminescent P.aeruginosa.

  20. Can microbial cells develop resistance to oxidative stress in antimicrobial photodynamic inactivation?

    Science.gov (United States)

    Kashef, Nasim; Hamblin, Michael R

    2017-03-01

    Infections have been a major cause of disease throughout the history of humans on earth. With the introduction of antibiotics, it was thought that infections had been conquered. However, bacteria have been able to develop resistance to antibiotics at an exponentially increasing rate. The growing threat from multi-drug resistant organisms calls for intensive action to prevent the emergence of totally resistant and untreatable infections. Novel, non-invasive, non-antibiotic strategies are needed that act more efficiently and faster than current antibiotics. One promising alternative is antimicrobial photodynamic inactivation (APDI), an approach that produces reactive oxygen species when dyes and light are combined. So far, it has been questionable if bacteria can develop resistance against APDI. This review paper gives an overview of recent studies concerning the susceptibility of bacteria towards oxidative stress, and suggests possible mechanisms of the development of APDI-resistance that should at least be addressed. Some ways to potentiate APDI and also to overcome future resistance are suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Potentiation by potassium iodide using TPPS4 for antimicrobial photodynamic inactivation

    Science.gov (United States)

    Huang, Liyi; Hamblin, Michael R.

    2018-02-01

    Potassium iodide can potentiate antimicrobial photodynamic inactivation (aPDI) of a broad-spectrum of microorganisms, producing many extra logs of killing. We compared two charged porphyrins, TPPS4 (thought to be anionic and not able to bind to Gram-negative bacteria) and TMPyP4 (considered cationic and well able to bind to bacteria). As expected TPPS4 + light did not kill Gram-negative Escherichia coli, but surprisingly when 100 mM KI was added, it was highly effective at mediating aPDI (eradication at 200 nM + 10 J/cm2 of 415 nm light). TPPS4 was more effective than TMPyP4 in eradicating the Gram-positive bacteria, methicillin-resistant Staphylococcus aureus and the fungal yeast Candida albicans (regardless of KI). TPPS4 was also highly active against E. coli after a centrifugation step when KI was added, suggesting that the supposedly anionic porphyrin bound to bacteria and Candida. We conclude that TPPS4 behaves as if it has some cationic character in the presence of bacteria, which may be related to its supply from vendors in the form of a dihydrochloride salt.

  2. Effect of wavelength, epidermal thickness and skin type on the required dose for photodynamic therapy

    CSIR Research Space (South Africa)

    Karsten, AE

    2008-10-01

    Full Text Available Effect of Wavelength, Epidermal Thickness and Skin Type on the Required Dose for Photodynamic Therapy A.E. Karsten1,2 1CSIR National Laser Centre, Biophotonics Group, PO Box 395, Pretoria, 0001, South Africa 2Physics Department, Faculty of Natural... a certain depth in the skin. For most laser treatments and diagnostics apllications, wavelengths ranging between 600 and 1 000 nm are used. 1.1 Photodynamic therapy (PDT) In South Africa, as in many other countries, cancer is a major health...

  3. In vitro evaluation of ruthenium complexes for photodynamic therapy.

    Science.gov (United States)

    Li, Wenna; Xie, Qiang; Lai, Linglin; Mo, Zhentao; Peng, Xiaofang; Leng, Ennian; Zhang, Dandan; Sun, Hongxia; Li, Yiqi; Mei, Wenjie; Gao, Shuying

    2017-06-01

    Photodynamic therapy (PDT) is a promising anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDT mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated. Photocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization. Mitochondrial membrane potential (MMP), cell apoptosis, DNA fragmentation, c-Myc gene expression, and telomerase activities were also assayed. Rup-03 and Rup-04 had the lowest IC 50 values. Rup-03 had an IC 50 value of 29.5±2.3μM in HepG2 cells and 59.0±6.1μM in RAW264.7 cells, while Rup-04 had an IC 50 value of 40.0±3.8μM in SGC-7901 cells. The complexes also induced cellular morphological changes and impaired cellular ability to scavenge ROS, and accumulated preferentially in mitochondria and endoplasmic reticulum. Rup-03 reduced MMP levels, induced apoptosis, and repressed both c-Myc mRNA expression and telomerase activity in HepG2 cells. Among six candidates, Rup-03-mediated PDT is most effective against HepG2 and RAW264.7, with a similar efficacy as that of Rup-04-mediated PDT against SGC-7901 cells. Repression of ROS scavenging activities and c-Myc expression, which mediated DNA damage-induced cell apoptosis and repression of telomerase activity, respectively, were found to be involved in the anticancer mechanisms of Rup-03. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. New design of textile light diffusers for photodynamic therapy

    International Nuclear Information System (INIS)

    Cochrane, Cédric; Mordon, Serge R.; Lesage, Jean Claude; Koncar, Vladan

    2013-01-01

    A homogeneous and reproducible fluence delivery rate during clinical photodynamic therapy (PDT) plays a determinant role in preventing under- or overtreatment. PDT applied in dermatology has been carried out with a wide variety of light sources delivering a broad range of more or less adapted light doses. Due to the complexities of the human anatomy, these light sources do not in fact deliver a uniform light distribution to the skin. Therefore, the development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of plastic optical fiber (POF) into textile structures could offer an interesting alternative. In this article, a textile light diffuser (TLD) has been developed using POF and Polyester yarns. Predetermined POF macrobending leads to side emission of light when the critical angle is exceeded. Therefore, a specific pattern based on different satin weaves has been developed in order to improve light emission homogeneity and to correct the decrease of side emitted radiation intensity along POF. The prototyped fabrics (approximately 100 cm 2 : 5 × 20 cm) were woven using a hand loom, then both ends of the POF were coupled to a laser diode (5 W, 635 nm). The fluence rate (mW/cm 2 ) and the homogeneity of light delivery by the TLD were evaluated. Temperature evolution, as a function of time, was controlled with an infrared thermographic camera. When using a power source of 5 W, the fluence rate of the TLD was 18 ± 2.5 mw/cm 2 . Due to the high efficiency of the TLD, the optical losses were very low. The TLD temperature elevation was 0.6 °C after 10 min of illumination. Our TLD meets the basic requirements for PDT: homogeneous light distribution and flexibility. It also proves that large (500 cm 2 ) textile light diffusers adapted to skin, but also to peritoneal or pleural cavity, PDTs can be easily produced by textile manufacturing processes

  5. Photodynamic therapy in patients with early central lung cancer

    Directory of Open Access Journals (Sweden)

    V. V. Sokolov

    2013-01-01

    Full Text Available The results of photodynamic therapy (PDT for early central lung cancer are represented in the article. The study included 37 patients (52 tumor lesions. For 52 lesions pre-invasive cancer (carcinoma in situ was determined in 6 cases, squamous cell cancer with invasion within mucosal and submucosal layers of bronchial wall – in 46 cases. 51 tumors were primary lesion, 1 – residual after radiotherapy. 17 of 37 patients underwent previous surgical or combined modality treatment for cancer in other anatomical sites. For PDT we used photosensitizers photogem, photosens and radachlorine. The treatment response was assessed 1 months later by data of endoscopy and morphological study, CT, US and endosonography. Complete regression was achieved in 86,5% of cases, partial regression – in 13,5%. The efficacy of PDT was depended on tumor size. For lesion up to 1 cm in size complete regression was in 100% of cases, from 1.5 cm to 2.0 cm – in 28.6%, for tumors more than 2 cm the complete regression was not achieved. The recurrence of tumor was diagnosed in 2 patients in the period from 1 to 5 years with following successful repeated courses of PDT. Adverse effects included inflammation changes in mucosa at the PDT region with transient (up to 6-7 days local fibrinous endobronchitis with obturation of segmental bronchial lumen by fibrin membranes (7 patients, scar stenosis of segmental bronchus (2 patients. All patients had increased sensitivity to sun exposure, mild skin burns at exposed areas of body were in 2 patients. The results showed that method was highly efficient and applicable for pre-invasive central lung cancer and in patients with multiple primary bronchial lesions and high risk of surgical complications. 

  6. Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Ali Seyed M

    2008-06-01

    Full Text Available Abstract Background Photodynamic therapy (PDT involves the administration of a tumor-localizing photosensitizing drug, which is activated by light of specific wavelength in the presence of molecular oxygen thus generating reactive oxygen species that is toxic to the tumor cells. PDT selectively destroys photosensitized tissue leading to various cellular and molecular responses. The present study was designed to examine the angiogenic responses at short (0.5 h and long (6 h drug light interval (DLI hypericin-PDT (HY-PDT treatment at 24 h and 30 days post treatment in a human bladder carcinoma xenograft model. As short DLI targets tumor vasculature and longer DLI induces greater cellular damage, we hypothesized a differential effect of these treatments on the expression of angiogenic factors. Results Immunohistochemistry (IHC results showed minimal CD31 stained endothelium at 24 h post short DLI PDT indicating extensive vascular damage. Angiogenic proteins such as vascular endothelial growth factor (VEGF, tumor necrosis growth factor-α (TNF-α, interferon-α (IFN-α and basic fibroblast growth factor (bFGF were expressed to a greater extent in cellular targeting long DLI PDT compared to vascular mediated short DLI PDT. Gene expression profiling for angiogenesis pathway demonstrated downregulation of adhesion molecules – cadherin 5, collagen alpha 1 and 3 at 24 h post treatment. Hepatocyte growth factor (HGF and Ephrin-A3 (EFNA3 were upregulated in all treatment groups suggesting a possible activation of c-Met and Ephrin-Eph signaling pathways. Conclusion In conclusion, long DLI HY-PDT induces upregulation of angiogenic proteins. Differential expression of genes involved in the angiogenesis pathway was observed in the various groups treated with HY-PDT.

  7. Canine treatment with SnET2 for photodynamic therapy

    Science.gov (United States)

    Frazier, Donita L.; Milligan, Andrew J.; Vo-Dinh, Tuan; Morgan, Alan R.; Overholt, Bergein F.

    1990-07-01

    Photodynamic therapy is a treatment technique that utilizes the photoactived species of a drug to destroy tumor tissue. To be successful, the drug must localize in tumor tissue preferentially over normal tissue and must be activated by light of a specific wavelength. Currently the only drug to be approved for clinical use is Heinatoporphyrin Derivative (HpD) although a series of new drugs are being developed for use in the near future. One of the drugs belongs to a class called purpurins which display absorp-' tions between 630-711 nm. Along with several other investigators, we are currently exploring the characteristics of a specific purpurin (SnET2) in normal and tumorous canine tissue. The use of this compound has demonstrated increased tumor control rates in spontaneous dog tumors. Preliminary pharmacokinetic studies have been performed on 6 normal beagle dogs. SnET2 (2 mg/kg) was injected intravenously over 10 minutes and blood was collected at 5, 15, 30, 45 minutes and at 1, 2, 4, 8, 12 and 24 hours following administration for determination of drug concentration and calculation of pharinacokinetic parameters. Skin biopsies were collected at 1, 4, 8, 12 and 24 hours. Dogs were euthanized at 24 hours and tissues (liver, kidney muscle, esophagus, stomach, duodenum, jejunum, ileura, colon, adrenal gland, thyroid, heart, lung, urinary bladder, prostate, pancreas, eye, brain) were collected for drug raeasurement. Drug was shown to persist in liver and kidney for a prolonged period of time coiapared to other tissues. Knowledge of the pharmacokinetic properties of the drug will greatly add to the ability to treat patients with effective protocols.

  8. Attaching NorA efflux pump inhibitors to methylene blue enhances antimicrobial photodynamic inactivation of Escherichia coli and Acinetobacter baumannii in vitro and in vivo.

    Science.gov (United States)

    Rineh, Ardeshir; Bremner, John B; Hamblin, Michael R; Ball, Anthony R; Tegos, George P; Kelso, Michael J

    2018-02-24

    Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en-MB that shows enhanced photodynamic inactivation of the Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) relative to MB, both in vitro and in vivo. Here, we report the surprising observation that INF55-(Ac)en-MB and two related hybrids bearing the NorA efflux pump inhibitors INF55 and INF271 also show enhanced aPDI activity in vitro (relative to MB) against the Gram-negative bacteria Escherichia coli and Acinetobacter baumannii, despite neither species expressing the NorA pump. Two of the hybrids showed superior effects to MB in murine aPDI infection models. The findings motivate wider exploration of aPDI with EPI-MB hybrids against Gram-negative pathogens and more detailed studies into the molecular mechanisms underpinning their activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilm in experimental primary and secondary endodontic infections.

    Science.gov (United States)

    Tennert, Christian; Feldmann, Katharina; Haamann, Edwina; Al-Ahmad, Ali; Follo, Marie; Wrbas, Karl-Thomas; Hellwig, Elmar; Altenburger, Markus J

    2014-11-04

    To determine the antibacterial effect of photodynamic Therapy on Enterococcus faecalis (E. faecalis) biofilms in experimentally infected human root canals in primary infections and endodontic retreatments. One hundred and sixty single-rooted extracted teeth with one root canal were prepared using ProTaper instruments. Seventy specimens were left without root canal filling and autoclaved. The root canals of another 70 specimens were filled with Thermafil and AH Plus and the root canal fillings were removed after 24 hours using ProTaper D files and plasma sterilized. The specimens were infected with a clinical isolate of E. faecalis for 72 hours. Samples were taken using sterile paper points to determine the presence of E. faecalis in the root canals. The specimens were randomly divided into groups according to their treatment with 20 teeth each and a control. In the PDT group the teeth were treated using PDT, consisting of the photosensitizer toluidine blue and the PDT light source at 635 nm. In the NaOCl (sodium hypochlorite) group the root canals were rinsed with 10 mL of 3% NaOCl. In the NaOCl-PDT group the root canals were rinsed with 10 mL of 3% of sodium hypochlorite and then treated with PDT. Samples were taken after treatments using sterile paper points. Additionally, remaining root canal filling material was recovered from the root canal walls. Survival fractions of the samples were calculated by counting colony-forming units. A one-way analysis of variance (ANOVA) was applied to the data to assess the effect of different treatment techniques. Antimicrobial treatment of root canals caused a significant reduction of bacterial load in all groups. NaOCl irrigation eliminated E. faecalis most effectively. PDT alone was less effective compared to NaOCl irrigation and the combination of NaOCl irrigation and PDT. CFU levels recovered from the filling material after NaOCl irrigation of the root canals were 10fold higher compared to PDT and the combination of Na

  10. Endodontic treatment of teeth with periapical lesion in one session with photodynamic therapy as an adjuvant: study "in vivo"

    OpenAIRE

    Supercilio Barros Filho

    2012-01-01

    Hypothesis of the study: It is assumed that the use of photodynamic therapy (PDT) as an adjuvant in root canal therapy can promote the repair of teeth with periapical lesions treated in one session. Objectives: This in vivo study was to evaluate the effects of photodynamic therapy as an adjuvant in root canal therapy in one session for the repair of periapical lesions. Method: Fourteen human teeth with mortification pulp and periapical lesions were randomly divided into two groups (n=7): G1- ...

  11. Studies of photodynamic therapy: Investigation of physiological mechanisms and dosimetry

    Science.gov (United States)

    Woodhams, Josephine Helen

    Photodynamic therapy (PDT) is a treatment for a range of malignant and benign lesions using light activated photosensitising drugs in the presence of molecular oxygen. PDT causes tissue damage by a combination of processes involving the production of reactive oxygen species (in particular singlet oxygen). Since the PDT cytotoxic effect depends on oxygen, monitoring of tissue oxygenation during PDT is important for understanding the basic physiological mechanisms and dosimetry of PDT. This thesis describes the use of non-invasive, optical techniques based on visible light reflectance spectroscopy for the measurement of oxy- to deoxyhaemoglobin ratio or haemoglobin oxygen saturation (HbSat). HbSat was monitored at tissue sites receiving different light dose during aluminium disulphonated phthalocyanine (AIS2PC) PDT. Results are presented on real time PDT-induced changes in HbSat in normal tissue (rat liver) and experimental tumours, and its correlation with the final biological effect under different light regimes, including fractionated light delivery. It was found to some extent that changes in HbSat could indicate whether the tissue would be necrotic after PDT and it was concluded that online physiological dosimetry is feasible for PDT. The evaluation of a new photosensitiser for PDT called palladium-bacteriopheophorbide (WST09) has been carried out in normal and tumour tissue in vivo. WST09 was found to exert a strong PDT effect but was active only shortly after administration. WST09 produced substantial necrosis in colonic tumours whilst only causing a small amount of damage to the normal colon under certain conditions indicating a degree of selectivity. Combination therapy with PDT for enhancing the extent of PDT-induced damage has been investigated in vivo by using the photochemical internalisation (PCI) technique and Type 1 mechanism enhanced phototoxicity with indole acetic acid (IAA). PCI of gelonin using AIS2PC PDT in vivo after systemic administration of

  12. Liposomes as a drug delivery system in photodynamic therapy for colon cancer treatment

    CSIR Research Space (South Africa)

    Maduray, K

    2010-01-01

    Full Text Available Photodynamic therapy (PDT) uses a drug termed a photosensitizer (PS), light (laser) of an appropriate wavelength and molecular oxygen (tissue) to elicit cell death of cancer cells. The objective of this study was to evaluate the enhancement of PDT...

  13. Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

    NARCIS (Netherlands)

    Karakullukcu, Baris; van Oudenaarde, Kim; Copper, Marcel P.; Klop, W. M. C.; van Veen, Robert; Wildeman, Maarten; Bing Tan, I.

    2011-01-01

    The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to

  14. Optical Spectroscopy to Guide Photodynamic Therapy of Head and Neck Tumors

    NARCIS (Netherlands)

    Robinson, Dominic J.; Karakullukcu, M. Baris; Kruijt, Bastiaan; Kanick, Stephen Chad; van Veen, Robert P. L.; Amelink, Arjen; Sterenborg, Henricus J. C. M.; Witjes, Max J. H.; Tan, I. Bing

    2010-01-01

    In contrast to other interstitial applications of photodynamic therapy (PDT), optical guidance or monitoring in the head and neck is at a very early stage of development. The present paper reviews the use of optical approaches, in particular optical spectroscopy, that have been used or have the

  15. Covalently Assembled NIR Nanoplatform for Simultaneous Fluorescence Imaging and Photodynamic Therapy of Cancer Cells

    NARCIS (Netherlands)

    Liu, Kai; Liu, Xiaomin; Zeng, Qinghui; Zhang, Youlin; Tu, Langping; Liu, Tao; Kong, Xianggui; Wang, Yinghui; Cao, Feng; Lambrechts, Saskia A. G.; Aalders, Maurice C. G.; Zhang, Hong

    2012-01-01

    A highly efficient multifunctional nanoplatform for simultaneous upconversion luminescence (UCL) Imaging and photodynamic therapy has been developed on the basis of selective energy transfer from multicolor luminescent NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs) to photosensitizers (PS).

  16. Photodynamic Therapy of Skin using Porphyrin Precursors: Optical Monitoring, Vascular Effects and Personalized Medicine

    NARCIS (Netherlands)

    T.A. Middelburg (Tom)

    2014-01-01

    markdownabstract__Abstract__ Photodynamic therapy (PDT) is based on a photochemical reaction that involves three basic components: (1) a photosensitizer, which is a light-sensitive molecule that mediates transfer of light energy to molecular oxygen; (2) light of the appropriate wavelength that

  17. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

    NARCIS (Netherlands)

    Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K.; van Wijk, Albert C.; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C.; van Gulik, Thomas M.; Storm, Gert; Heger, Michal

    2016-01-01

    Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of

  18. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

    NARCIS (Netherlands)

    Weijer, R.; Broekgaarden, M.; Krekorian, M.; Alles, L.K.; van Wijk, A.C; Mackaaij, C.; Verheij, J.; van der Wal, A.C.; van Gullik, T.M.; Storm, Gerrit; Heger, M.

    2016-01-01

    Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression

  19. Photodynamic therapy with verteporfin: observations on the introduction of a new treatment into clinical practice.

    Science.gov (United States)

    Schein, Oliver D; Bressler, Neil M; Price, Patrick

    2005-01-01

    To assess adherence to Food and Drug Administration-approved indications and Centers for Medicare & Medicaid Services policy through June 2001 regarding the use of photodynamic therapy in Medicare beneficiaries. Systematic review of pretreatment fluorescein angiograms of 1245 consecutive Medicare patients who received photodynamic therapy from physicians in 3 contiguous Medicare coverage areas (fee-for-service arrangement) and in 136 consecutive patients in a Medicare health maintenance organization. In the 3 Medicare fee-for-service regions, payment denial due to nonconforming fluorescein angiograms ranged from 17% to 29% by region in 1245 beneficiaries. In the health maintenance organization setting, 60 (44%) of 136 submitted angiograms were nonconforming, including 8 in which the photographic quality was too poor to grade the lesion size, composition, or both. A substantial proportion of the actual or intended clinical application of photodynamic therapy with verteporfin was directed to patients who did not meet concurrent published clinical criteria associated with treatment benefit or national coverage policy. Although this policy has evolved, it still depends on fluorescein angiographic interpretation, suggesting that there is an opportunity to improve the cost-effectiveness of delivery of photodynamic therapy with verteporfin to Medicare beneficiaries.

  20. Covalently assembled NIR nanoplatform for simultaneous fluorescence imaging and photodynamic therapy of cancer cells

    NARCIS (Netherlands)

    Liu, K.; Liu, X.; Zeng, Q.; Zhang, Y.; Tu, L.; Liu, T.; Kong, X.; Wang, Y.; Cao, F.; Lambrechts, S.A.G.; Aalders, M.C.G.; Zhang, H.

    2012-01-01

    A highly efficient multifunctional nanoplatform for simultaneous upconversion luminescence (UCL) imaging and photodynamic therapy has been developed on the basis of selective energy transfer from multicolor luminescent NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs) to photosensitizers (PS).

  1. Is the thin layer of methyl aminolevulinate used during photodynamic therapy sufficient?

    DEFF Research Database (Denmark)

    Wiegell, Stine R; Lerche, Catharina M; Wulf, Hans Christian

    2016-01-01

    BACKGROUND: If the recommended 1.0 mm layer of methyl aminolevulinate (MAL) is used during photodynamic therapy (PDT) of large areas with multiple actinic keratoses (AK) huge amounts of cream are needed. OBJECTIVES: To report the amount of MAL used for PDT of AK and basal cell carcinomas (BCC) in...

  2. Diffuse choroidal haemangioma in Sturge-Weber syndrome treated with photodynamic therapy under general anaesthesia

    NARCIS (Netherlands)

    Huiskamp, EA; Muskens, RPHM; Ballast, A; Hooymans, JMM

    Purpose: To report the treatment outcome of photodynamic therapy with verteporfin (PDT) for exudative retinal detachment associated with diffuse choroidal haemangioma in Sturge-Weber syndrome. Methods: An interventional case report of a 12-year-old girl with Sturge-Weber syndrome who developed an

  3. Photodynamic therapy of necrobiosis lipoidica--a multicenter study of 18 patients

    DEFF Research Database (Denmark)

    Berking, C; Hegyi, J; Arenberger, P

    2008-01-01

    BACKGROUND: Necrobiosis lipoidica (NL) is a granulomatous skin disease of unknown origin, and no reliably effective treatment option exists to handle this often disfiguring disease. Recently, a patient with long-lasting NL was reported to be cured by topical photodynamic therapy (PDT). OBJECTIVE:...

  4. Precise Photodynamic Therapy of Cancer via Subcellular Dynamic Tracing of Dual-loaded Upconversion Nanophotosensitizers

    NARCIS (Netherlands)

    Chang, Y.; Li, X.; Zhang, L.; Xia, L.; Liu, Xiaomin; Li, C.; Zhang, Y.; Tu, L.; Xue, B.; Zhao, H.; Zhang, H.; Kong, X.

    2017-01-01

    Recent advances in upconversion nanophotosensitizers (UCNPs-PS) excited by near-infrared (NIR) light have led to substantial progress in improving photodynamic therapy (PDT) of cancer. For a successful PDT, subcellular organelles are promising therapeutic targets for reaching a satisfactory

  5. Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers

    Science.gov (United States)

    Chissov, Valery I.; Sokolov, Victor V.; Trakhtenberg, A. K.; Mamontov, A. S.; Vaschakmadze, L. A.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Belous, T. A.; Gladunov, V. K.; Aristarkhova, E. I.; Zharkova, Natalia N.; Menenkov, V. D.

    1996-01-01

    The paper presents the results of photodynamic therapy (PDT) of early-stage cancer of lung (17 patients), esophagus (8 patients) and stomach (10 patients). Fifteen patients had second primary tumors. New drugs photoheme and photosens were used as photosensitizers. Complete remission was obtained in 87%. The patients are followed up without relapses to 2.5 years.

  6. Effect of photodynamic therapy in the reduction of halitosis in patients with multiple sclerosis: clinical trial.

    Science.gov (United States)

    Gonçalves, Marcela Leticia Leal; Kalil Bussadori, Sandra; Dadalti Fragoso, Yara; da Silva, Vinicius Vieira Belarmino; Melo Deana, Alessandro; da Mota, Ana Carolina Costa; Horácio Pinto, Erika; Horliana, Anna Carolina RattoTempestini; Miranda França, Cristiane

    2017-10-27

    Smell and odours play a vital role in social interaction. Halitosis is a social problem that affects one third of the population, causing a negative impact on the quality of life. There is little knowledge on the prevalence and management of halitosis in multiple sclerosis (MS) patients. The present study aims to evaluate the presence of halitosis in patients with MS when compared to a control group, and also evaluate treatment of the problem with antimicrobial photodynamic therapy (aPDT). This is a case-control clinical study in which 60 patients were evaluated: 30 MS patients in treatment at the Specialties Clinic School of Medicine, and 30 healthy patients, matched in age and gender for the control group. Data was collected on the duration of the disease as well as the degree of disability and medication use in the MS group. For all patients, halitosis was assessed with Oral Chroma™. Individuals with halitosis underwent treatment with tongue scraping and aPDT. The photosensitizer was methylene blue (0.005%) and a THERAPY XT-EC ® laser (660 nm, 9 J, 100 mW for 90 s per point, 320 J cm -2 , 3537 mW cm -2 ) was used. Six points 1 cm apart from each other were irradiated in the tongue dorsum. There was a positive correlation between the disability and disease duration. No parameter was correlated with halitosis. Patients with MS have higher levels of SH 2 compounds when compared to the control group (p = 0.003, Mann-Whitney), but after aPDT both groups significantly reduced the levels to under the halitosis threshold. The aPDT scraping treatment was effective in the immediate reduction of halitosis in both groups.

  7. Local and systemic antimicrobial therapy in periodontics.

    Science.gov (United States)

    Herrera, David; Matesanz, Paula; Bascones-Martínez, Antonio; Sanz, Mariano

    2012-09-01

    This review aimed to update the current evidence on the efficacy of the adjunctive use of local and systemic antimicrobials in the treatment of periodontitis and to assess whether it might improve the clinical limitations and shortcomings of standard nonsurgical treatment in the management of periodontitis. Relevant randomized clinical trials (RCT) with more than 3 months of follow-up, published from 2010 to 2012 for systemic antimicrobials and from 2008 to 2012 for local antimicrobials, were searched in Medline and critically analyzed. Scientific evidence evaluated in different systematic reviews and reviews presented at European and World Workshops were also included. Only adjunctive therapies were considered in the present review: articles comparing debridement alone or plus placebo, versus debridement plus systemic or local antimicrobials were included. Adjunctive systemic antimicrobials have been evaluated both in aggressive and chronic periodontitis: in aggressive periodontitis, amoxicillin and metronidazole have been extensively studied, reporting clinical and microbiological benefits; in chronic periodontitis, different products are under scrutiny, such as azithromycin. The clinical efficacy of local antimicrobials, although extensively demonstrated, is still surrounded by a constant debate on the cost-effectiveness evaluation and on its adequate indications. Despite the clinical efficacy of the adjunctive use of local and systemic antimicrobials, demonstrated in RCTs and in systematic reviews, there is a lack of evidence to support well-defined clinical protocols, including products and dosages. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Biomedical applications of nano-titania in theranostics and photodynamic therapy.

    Science.gov (United States)

    Rehman, F U; Zhao, C; Jiang, H; Wang, X

    2016-01-01

    Titanium dioxide (TiO2) is one of the most abundantly used nanomaterials for human life. It is used in sunscreen, photovoltaic devices, biomedical applications and as a food additive and environmental scavenger. Nano-TiO2 in biomedical applications is well documented. It is used in endoprosthetic implants and early theranostics of neoplastic and non-neoplastic maladies as a photodynamic therapeutic agent and as vehicles in nano-drug delivery systems. Herein, we focus on the recent advancements and applications of nano-TiO2 in bio-nanotechnology, nanomedicine and photodynamic therapy (PDT).

  9. Multifunctional gold nanoparticles for photodynamic therapy of cancer

    Science.gov (United States)

    Khaing Oo, Maung Kyaw

    As an important and growing branch of photomedicine, photodynamic therapy (PDT) is being increasingly employed in clinical applications particularly for the treatment of skin cancer. This dissertation focuses on the synthesis, characterization and deployment of gold nanoparticles for enhanced PDT of fibrosarcoma cancer cells. We have developed robust strategies and methods in fabrication of gold nanoparticles with positively- and negatively-tethered surface charges by photo-reduction of gold chloride salt using branched polyethyleneimine and sodium citrate respectively. An optimal concentration window of gold salt has been established to yield the most stable and monodispersed gold nanoparticles. 5-aminolevulinic acid (5-ALA), a photosensitizing precursor, has been successfully conjugated on to positively charged gold nanoparticles through electrostatic interactions. The 5-ALA/gold nanoparticle conjugates are biocompatible and have shown to be preferably taken up by cancer cells. Subsequent light irradiation results in the generation of reactive oxygen species (ROS) in cancer cells, leading to their destruction without adverse effects on normal fibroblasts. We have demonstrated for the first time that gold nanoparticles can enhance PDT efficacy by 50% compared to the treatment with 5-ALA alone. Collected evidence has strongly suggested that this enhancement stems from the elevated formation of ROS via the strongly localized electric field of gold nanoparticles. Through single cell imaging using surface-enhanced Raman scattering enabled by the very same gold nanoparticles, we have shown that multifunctionality of gold nanoparticles can be harvested concurrently for biomedical applications in general and for PDT in specific. In other words, gold nanoparticles can be used not only for targeted drug delivery and field-enhanced ROS formation, but also for monitoring cell destructions during PDT. Finally, our COMSOL Multiphysics simulation of the size-dependent electric

  10. 5-Aminolevulinic acid photodynamic therapy for superficial basal cell carcinoma

    International Nuclear Information System (INIS)

    Want, David; Kennedy, James C.; Brundage, Michael; Rothwell, Deanna

    1997-01-01

    Treatment of superficial basal cell carcinoma with topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) offers an alternative to plastic surgery and radiotherapy with potential for good cosmetic outcome and local control of disease. We report our clinical experience with this technique. Patients were treated prospectively on a study protocol enrolling a total of 118 patients (63 male, 55 female) with an average age of 65 years. Consecutive patients meeting eligibility criteria were invited to participate over a four year period. Median followup was 27 months (range 1 to 76 months). In the study group, 62 patients had single lesions and 56 had multiple lesions. Of the 56 patients with multiple lesions, 33 had 2-4 lesions, 11 had 5-9, and 11 had 10 or more. All patients were treated with 20% ALA dissolved in Glaxal Base applied to the tumors for three to four hours. Following removal of the cream, fluorescence intensity and distribution were assessed using a UV-A lamp, and the lesions were exposed to photoactivating light of wavelength greater than 600 nm for a light dose ranging from 100-150 J/cm2. Lesions were reassessed in followup, and scored as complete or partial responses. At subsequent patient assessments, lesions were scored as continued complete responses or recurrences. In the patients with single lesions, there was an initial complete response rate of 90.3%. Of the 56 patients with multiple lesions, 44 had all of their lesions respond completely, and there was an overall average response rate of 95.5%. Sixty three percent of males and 44% of females had all of their lesions respond completely. (p=0.033, Chi-squared test). There was no difference in response rate with respect to age, or site of lesion. The recurrence rates were 35% for patients with single lesions, and 10.5% for patients with multiple lesions. ALA-PDT would appear to be a promising alternative to conventional treatment for superficial basal cell carcinoma. Based on these results

  11. MULTIPLE-COURSE PHOTODYNAMIC THERAPY FOR VERRUCOUS LEUKOPLAKIA OF MUCOUS MEMBRANE OF BODY OF THE TONGUE (CASE REPORT

    Directory of Open Access Journals (Sweden)

    Yu. P. Istomin

    2016-01-01

    Full Text Available The results of treatment of the patient with verrucous luekoplakia of mucous membrane of body of the tongue with photodynamic therapy are represented. In 2015 the patient underwent 4 courses of photodynamic therapy with photosensitizer photolon. Photolon was injected at dose of 2 mg/kg 3 h before irradiation (laser output power was 0.262 W, light dose – 50 and 100 J/cm2. The result of treatment was assessed as complete regression: 4 months after multiple-course photodynamic therapy there were no clinical and histological signs of luekoplakia.

  12. Current resistance issues in antimicrobial therapy | Senekal ...

    African Journals Online (AJOL)

    The human gut contains 1013 - 1014 bacteria that are exposed to selection pressure whenever antibiotics are administered.1 The same selection pressure applies to respiratory flora, which is one of the reasons why antimicrobial therapy prescribed for the treatment of respiratory tract infection should aim to eradicate ...

  13. EXPERIMENTAL CONFIRMATION FOR SELECTION OF IRRADIATION REGIMENS FOR INTRAPERITONEAL PHOTODYNAMIC THERAPY WITH PORPHYRIN AND PHTHALOCYANINE PHOTOSENSITIZERS

    Directory of Open Access Journals (Sweden)

    A. A. Pankratov

    2017-01-01

    Full Text Available Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.The experimental  study on НЕр2 cell line showed that reduce of power density for constant  light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death for half as much concentration of the photosensitizer.The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2  and power density of 25 mW/cm2 none of animals in the experimental  group had total resorption of the tumor. For the same light dose and decrease  of power density to 12 mW/cm2  total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic  shock. For twofold decrease  of light dose – to 45 J/cm2  with the same low-intensity power density (12 mW/cm2 we managed total tumor resorption in 100% of animals.In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2  with power density of mW/cm2.Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.

  14. Attempted photodynamic therapy against patagial squamous cell carcinoma in an African rose-ringed parakeet (Psittacula krameri).

    Science.gov (United States)

    Suedmeyer, Wm Kirk; Henry, Carolyn; McCaw, Dudley; Boucher, Magalie

    2007-12-01

    A 5-yr-old female African rose-ringed parakeet (Psittacula krameri) presented with an ulcerated mass in the medial postpatagial area of the right wing. Biopsy specimens of the mass demonstrated a well-differentiated squamous cell carcinoma. Photodynamic therapy resulted in tumor cell necrosis and initial reduction in tumor burden, but complete remission was not achieved. Based on this and other avian cases, it appears that photodynamic therapy designed to eradicate squamous cell carcinoma in avian species using protocols modeled after canine, feline, and human photodynamic therapy protocols may not be useful. It is hypothesized that differences in light penetration, photosensitizing agent pharmacokinetics, and wound healing properties in avian species necessitate alteration of photodynamic therapy protocols if this treatment modality is to be effective in avian oncology.

  15. Porous Porphyrin-Based Organosilica Nanoparticles for NIR Two-Photon Photodynamic Therapy and Gene Delivery in Zebrafish

    KAUST Repository

    Mauriello Jimenez, Chiara; Aggad, Dina; Croissant, Jonas G.; Tresfield, Karen; Laurencin, Danielle; Berthomieu, Dorothé e; Cubedo, Nicolas; Rossel, Mireille; Alsaiari, Shahad K.; Anjum, Dalaver H.; Sougrat, Rachid; Roldan-Gutierrez, Manuel A.; Richeter, Sé bastien; Oliviero, Erwan; Raehm, Laurence; Charnay, Clarence; Cattoë n, Xavier; Clé ment, Sé bastien; Wong Chi Man, Michel; Maynadier, Marie; Chaleix, Vincent; Sol, Vincent; Garcia, Marcel; Gary-Bobo, Magali; Khashab, Niveen M.; Bettache, Nadir; Durand, Jean-Olivier

    2018-01-01

    functionalization of the nanoparticles with aminopropyltriethoxysilane, two-photon-excited photodynamic therapy in zebrafish is successfully achieved. Two-photon photochemical internalization in cancer cells of the nanoparticles loaded with siRNA is also performed

  16. Photodynamic therapy in non-surgical treatment of chronic periodontitis: short term randomized clinical trial study

    Science.gov (United States)

    Russo, C.; Palaia, G.; Loskutova, E.; Libotte, F.; Kornblit, R.; Gaimari, G.; Tenore, G.; Romeo, U.

    2016-03-01

    Introduction: Periodontitis is a chronic inflammatory disease due to exposition to plaque and tartar. Conventional treatments consist of scaling and root planing (SRP) and antibiotics administration. Among them encouraging results have been obtained using alternative protocols, like the antimicrobial photodynamic therapy (PDT). Aim of the Study: Evaluation of PDT effects added to conventional methods. Materials and Methods: 11 patients (4M/7F, 37-67 years aged, non-smoking) affected by untreated chronic periodontal disease, with >3mm pockets in at least 4 teeth were divided in two groups, test and control group. Each patient had to made full-intraoral before and after the treatment. The test group received SRP+PDT, while the control group was subjected to SRP. The PDT was performed through the HELBO®TheraLite (Bredent Medical), diode laser battery powered 670nm with an output of 75mW/cm2. The Helbo Blue photosensitizer, containing methylene blue, was used. The exposure time to the laser effect was of 10'' for each site, for a total of 60'' at 3J/cm2. Results: Both groups had a significant improvement in the reduction of pocket depth (PD), above all in the test group. Statistical analysis was performed through the T-test, evaluating PD between the two groups p=0.96 (p> 0.05), resulting not statistically significant. Conclusion: PDT is a promising support to SRP, achieving a significant reduction in the pocket depth, but more cases are needed to confirm the validity of the used protocol.

  17. 5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies

    Science.gov (United States)

    Nelius, Thomas; de Riese, Werner T. W.

    2003-06-01

    Completeness and certainty of tumor detection are very important issues in clinical oncology. Recent technological developments in ultrasound, radiologic and magnetic resonance imaging diagnostics are very promising, but could not improve the detection rate of early stage malignancies. One of the most promising new approaches is the use of 5-aminolevulinic acid, a potent photosensitizer, in photodynamic diagnosis and therapy. 5-aminolevulinic acid is meanwhile a well-established tool in the photodynamic diagnosis of bladder cancer. It has been shown to improve the sensitivity of detection of superficial tumors and carcinoma in situ, which enables to reduce the risk of tumor recurrence related to undetected lesions or incomplete transurethral resection of the primary lesions. The use of 5-aminolevulinic acid is steadily expanding in diagnostics of urological malignancies. First clinical results are now reported in detection of urethral and ureteral lesions as well as in urine fluorescence cytology. Furthermore, due to the selective accumulation in transitional cell carcinoma of the bladder, 5-aminolevulinic acid may be an ideal candidate for photodynamic therapy in superficial bladder cancer. Summarizing the data of multiple clinical trials, 5-aminolevulinic acid is a promising agent in photodynamic diagnostics and treatment of superficial bladder cancer.

  18. Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

    Science.gov (United States)

    Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

    2015-09-01

    Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. COMPARATIVE STUDIES OF EFFICACY OF PHOTODYNAMIC THERAPY AND CRYOTHERAPY FOR TREATMENT OF ACTINIC KERATOSIS

    Directory of Open Access Journals (Sweden)

    T. E. Sukhova

    2016-01-01

    Full Text Available The results of a study on the effectiveness of photodynamic therapy with a photosensitizer fotoditazin and cryotherapy for actinic keratosis are represented in the article. The study included 80 patients with 215 lesions, among them erythematous form of actinic keratosis was diagnosed in 151 (70.2% cases, hyperkeratotic form – in 46 (21.4% cases, a pigmented form – in 12 (5.6% and an atypical variant of the disease – in 6 (2.8% cases. According to histological type the distribution of tumor was as follows: 19 (54.3% cases were diagnosed as hypertrophic type, 6 (17.1% – atrophic, 8 (22.9% – bowenoid and 2 (5.7% – pigmented type. Patients from the study group received one session of photodynamic therapy using laser unit "LAMI" (662 nm after 2 hours of application of fotoditazin 0.5% gel at dose of 0,2-0,3 ml per 1 cm2 of actinic keratosis focus with the following parameters: the energy density of the laser radiation – 200 J/cm2, power density – 0.14–0.48 W/cm2. In the control group patients underwent cryotherapy with liquid nitrogen with an exposure of 30-60 sec. The comparative analysis of the immediate results showed a tendency for the efficacy of photodynamic therapy to increase (the rate of complete regression was 92.5% compared with cryotherapy (85.0% (p>0,05. There were also a tendency for long-term results after photodynamic therapy to improve: three-year recurrence-free survival was 94.6% and 88.2%, respectively. For the photodynamic therapy there were significantly fewer adverse reactions, the epithelization time in lesions was significantly shorter. Compared with cryotherapy the photodynamic therapy provided significantly better cosmetic results (p <0.01, and can be used for out-patient treatment of patients with actinic keratosis.><0.01 and can be used for out-patient treatment of patients with actinic keratosis.

  20. Conjugate of biotin with silicon(IV) phthalocyanine for tumor-targeting photodynamic therapy.

    Science.gov (United States)

    Li, Ke; Qiu, Ling; Liu, Qingzhu; Lv, Gaochao; Zhao, Xueyu; Wang, Shanshan; Lin, Jianguo

    2017-09-01

    In order to improve the efficacy of photodynamic therapy (PDT), biotin was axially conjugated with silicon(IV) phthalocyanine (SiPc) skeleton to develop a new tumor-targeting photosensitizer SiPc-biotin. The target compound SiPc-biotin showed much higher binding affinity toward BR-positive (biotin receptor overexpressed) HeLa human cervical carcinoma cells than its precursor SiPc-pip. However, when the biotin receptors of HeLa cells were blocked by free biotin, >50% uptake of SiPc-biotin was suppressed, demonstrating that SiPc-biotin could selectively accumulate in BR-positive cancer cells via the BR-mediated internalization. The confocal fluorescence images further confirmed the target binding ability of SiPc-biotin. As a consequence of specificity of SiPc-biotin toward BR-positive HeLa cells, the photodynamic effect was also largely dependent on the BR expression level of HeLa cells. The photodynamic activities of SiPc-biotin against HeLa cells were dramatically reduced when the biotin receptors were blocked by the free biotin (IC 50 : 0.18μM vs. 0.46μM). It is concluded that SiPc-biotin can selectively damage BR-positive cancer cells under irradiation. Furthermore, the dark toxicity of SiPc-biotin toward human normal liver cell lines LO2 was much lower than that of its precursor SiPc-pip. The targeting photodynamic activity and low dark toxicity suggest that SiPc-biotin is a promising photosensitizer for tumor-targeting photodynamic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Effectiveness of Photodynamic Therapy in the Healing of Corneal Alkali Burn in Rats

    Directory of Open Access Journals (Sweden)

    Akshay Khera

    2016-06-01

    Full Text Available In this study, we investigated the effect of photodynamic therapy (PDT on the healing of corneal alkali burns in rats. The experiment was performed on 50 adult non-linear rats. Depending on the intervention, the animals were divided into 5 equal groups with 10 animals in each group: Group 1 included rats with intact eyes (the control group and Groups 2 through 5 were experimental groups with EAB. Group 2 consisted of rats subjected to instillation of 0.25% chloramphenicol solution; Group 3 consisted of rats subjected to photodynamic irradiation according to our scheme: 300 mJ (630 nm for 3 minutes; Group 4 consisted of rats subjected to instillation of methylene blue (MB; Group 5 consisted of rats subjected to instillation of MB with subsequent photodynamic irradiation according to the described scheme. During all periods of observation, the infiltration of the subcorneal zone was less pronounced in Group 5 than in the other groups and was represented mainly by round cells in the anterior chamber, iris, retina, and ciliary zone. The instillation of MB with subsequent photodynamic irradiation was the most effective in reducing the bacterial contamination Thus, PDT with the photosensitizer methylene blue, in accordance with the designed exposure mode, provided the epithelialization and bacteriostatic effect during corneal repair after EAB. In conclusion, PDT improves a wound’s healing process, which is expressed in the reduction of inflammatory infiltration and the promotion of corneal epithelialization.

  2. Three-dimensional in vitro cancer spheroid models for Photodynamic Therapy: Strengths and Opportunities

    Science.gov (United States)

    Evans, Conor

    2015-03-01

    Three dimensional, in vitro spheroid cultures offer considerable utility for the development and testing of anticancer photodynamic therapy regimens. More complex than monolayer cultures, three-dimensional spheroid systems replicate many of the important cell-cell and cell-matrix interactions that modulate treatment response in vivo. Simple enough to be grown by the thousands and small enough to be optically interrogated, spheroid cultures lend themselves to high-content and high-throughput imaging approaches. These advantages have enabled studies investigating photosensitizer uptake, spatiotemporal patterns of therapeutic response, alterations in oxygen diffusion and consumption during therapy, and the exploration of mechanisms that underlie therapeutic synergy. The use of quantitative imaging methods, in particular, has accelerated the pace of three-dimensional in vitro photodynamic therapy studies, enabling the rapid compilation of multiple treatment response parameters in a single experiment. Improvements in model cultures, the creation of new molecular probes of cell state and function, and innovations in imaging toolkits will be important for the advancement of spheroid culture systems for future photodynamic therapy studies.

  3. Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

    International Nuclear Information System (INIS)

    Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

    2009-01-01

    Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

  4. Review of photodynamic therapy in actinic keratosis and basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Marica B Ericson

    2008-03-01

    Full Text Available Marica B Ericson1,2, Ann-Marie Wennberg1, Olle Larkö11Department of Dermatology; 2Department of Physics, Göteborg University, Göteborg, SwedenAbstract: The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field.Keywords: photodynamic therapy, actinic keratosis, basal cell carcinoma

  5. Optimum modality for photodynamic therapy of tumors: gels containing liposomes with hydrophobic photosensitizers

    Czech Academy of Sciences Publication Activity Database

    Nekvasil, Miloš; Zadinová, M.; Tahotná, Ludmila; Žáčková, Markéta; Poučková, P.; Ježek, Petr

    2007-01-01

    Roč. 68, č. 5 (2007), s. 235-252 ISSN 0272-4391 R&D Projects: GA MŠk 1P04OE152; GA MPO 2A-1TP1/026; GA MZd NC6564 Institutional research plan: CEZ:AV0Z50110509 Keywords : photodynamic therapy of tumors * liposomal photosensitizer gel * hydroxyl-aluminium phtalocyanine * microfluidizacion Subject RIV: FD - Oncology ; Hematology Impact factor: 0.976, year: 2007

  6. A laser unit for photodynamic therapy and robot-assisted microsurgery in dentistry

    Science.gov (United States)

    Chunikhin, A. A.; Bazikyan, E. A.; Pikhtin, N. A.

    2017-06-01

    Results are presented of photochemical experiments with an IR-laser unit for microsurgery and photodynamic therapy in dentistry. The efficiency of direct generation of singlet oxygen in model organic media in the continuous-wave and pulsed nanosecond modes is examined. The unit can serve both as an independent instrument and as a part of a complex for robot-assisted surgery and dentistry.

  7. Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens

    OpenAIRE

    Smith, TK; Choi, B; Ramirez-San-Juan, JC; Nelson, JS; Osann, K; Kelly, KM

    2006-01-01

    Background and Objectives: Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT/ PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT/PDL in an in vivo rodent dorsal skinfold model. Study Design/Materials and Methods: A dorsal sk...

  8. Novel Topical Photodynamic Therapy of Prostate Carcinoma Using Hydroxy-aluminum Phthalocyanine Entrapped in Liposomes

    Czech Academy of Sciences Publication Activity Database

    Sutoris, K.; Rakušan, J.; Karásková, M.; Mattová, J.; Beneš, J.; Nekvasil, Miloš; Ježek, Petr; Zadinová, M.; Poučková, P.; Větvička, D.

    2013-01-01

    Roč. 33, č. 4 (2013), s. 1563-1568 ISSN 0250-7005 R&D Projects: GA MPO(CZ) 2A-1TP1/026; GA MŠk(CZ) OE09026; GA TA ČR(CZ) TA01010781 Institutional support: RVO:67985823 Keywords : PC prostate carcinomas * LNCaP * liposomes * hydroxy-aluminum phthalocyanine * photodynamic therapy Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.872, year: 2013

  9. Photodynamic therapy and imaging based on tumor-targeted nanoprobe, polymer-conjugated zinc protoporphyrin

    Czech Academy of Sciences Publication Activity Database

    Fang, J.; Liao, L.; Yin, H.; Nakamura, H.; Šubr, Vladimír; Ulbrich, Karel; Maeda, H.

    2015-01-01

    Roč. 2015, č. 4 (2015), s. 1-13 ISSN 2056-5623 R&D Projects: GA ČR(CZ) GAP301/12/1254 Grant - others:AV ČR(CZ) AP0802 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:61389013 Keywords : fluorescent nanoprobe * photodynamic therapy * theranostic nanomedicine Subject RIV: CD - Macromolecular Chemistry

  10. Photodynamic therapy effect of aluminum and zinc tetrasulfophthalocyanines on melanoma cancer cells

    CSIR Research Space (South Africa)

    Maduray, K

    2010-06-01

    Full Text Available , Cancer, Aluminum Tetrasulfophthalocyanines, Zinc Tetrasulfophthalocyanines 1. INTRODUCTION Photodynamic therapy (PDT) is a promising oncology treatment which aims at offering treatment that is selective and localized. PDT is a very simple principle... which requires three essential components a photosensitizer (PS), visible light (laser source) and molecular oxygen present in the biological tissue. The combination of these components will result in the destruction of tumor cells.1 This oncology...

  11. Two-photon excitation of porphyrin-functionalized porous silicon nanoparticles for photodynamic therapy.

    Science.gov (United States)

    Secret, Emilie; Maynadier, Marie; Gallud, Audrey; Chaix, Arnaud; Bouffard, Elise; Gary-Bobo, Magali; Marcotte, Nathalie; Mongin, Olivier; El Cheikh, Khaled; Hugues, Vincent; Auffan, Mélanie; Frochot, Céline; Morère, Alain; Maillard, Philippe; Blanchard-Desce, Mireille; Sailor, Michael J; Garcia, Marcel; Durand, Jean-Olivier; Cunin, Frédérique

    2014-12-03

    Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. 0.5% Liposome-encapsulated 5-aminolevulinic acid (ALA) photodynamic therapy for acne treatment.

    Science.gov (United States)

    An, Jee-Soo; Kim, Jeong-Eun; Lee, Dong-Hun; Kim, Byung-Yoon; Cho, Soyun; Kwon, In-Ho; Choi, Won-Woo; Kang, Seong-Min; Won, Chong-Hyun; Chang, Sung-Eun; Lee, Mi-Woo; Choi, Jee-Ho; Moon, Kee-Chan

    2011-02-01

    Photodynamic therapy using topical 5-aminolevulinic acid (ALA) has been successful in treating acne vulgaris, but sun avoidance for at least 48 hours after treatment is necessary due to the risk of post-treatment photosensitivity. Recently, a lower concentration of liposome-encapsulated 5-ALA was introduced to minimize this risk. To evaluate the efficacy and safety of liposome-encapsulated 0.5% 5-ALA in the photodynamic therapy of inflammatory acne and its effects on sebum secretion in Asian skin. Thirteen Korean subjects with inflammatory acne were administered 0.5% ALA spray before photoradiation treatment. Photoradiation was performed at 3.5-6.0 J/cm(2) three times during each of two visits, performed 2 weeks apart. Improvement of acne was evaluated subjectively and objectively based on the Korean Acne Grading System. Sebum secretion was measured quantitatively at each visit. The mean reduction in acne grade at the end of the treatment was 43.2%. Of the patients, 69.2% reported improvements in subjective skin oiliness, but fewer showed objective reductions in sebum secretion as determined by the Sebumeter® SM10. No serious adverse events were observed. Photodynamic therapy using liposome-encapsulated 0.5% 5-ALA improved inflammatory acne with minimal side effects in Asians.

  13. Afterglow properties of CaF2:Tm nanoparticles and its potential application in photodynamic therapy

    International Nuclear Information System (INIS)

    Zahedifar, M.; Sadeghi, E.; Shanei, M.M.; Sazgarnia, A.; Mehrabi, M.

    2016-01-01

    CaF 2 :Tm nanoparticles (NPs) were synthesized by the hydrothermal method. Intense afterglow emission with long life time was found for the produced NPs, so its applicability in photodynamic therapy was investigated. Since the wavelength of the afterglow emission of the NPs fairly matches with the absorption band of the PpIX sensitizer, especially in the red region, the Cystein mediator was used to bond NPs with the PpIX sensitizer. The CaF 2 :Tm NPs conjugated with PpIX was exposed to X-ray and by using the Antracene as detector, the production of the singlet oxygen was verified. Therefore, the produced NPs are recommended as a source of energy that improves photodynamic therapy beyond its current limitations. - Highlights: • Intense afterglow emission found for the synthesized CaF 2 :Tm nanoparticles. • CaF 2 :Tm emission band fairly matched with PpIX sensitizer's absorption band. • CaF 2 :Tm conjugated with the sensitized is a good candidate for photodynamic therapy. • The application of nanoparticles in producing singlet oxygen was verified.

  14. Optimization and Evaluation of a Chitosan/Hydroxypropyl Methylcellulose Hydrogel Containing Toluidine Blue O for Antimicrobial Photodynamic Inactivation

    Directory of Open Access Journals (Sweden)

    Chueh-Pin Chen

    2015-09-01

    Full Text Available Photodynamic inactivation (PDI combined with chitosan has been shown as a promising antimicrobial approach. The purpose of this study was to develop a chitosan hydrogel containing hydroxypropyl methylcellulose (HPMC, chitosan and toluidine blue O (TBO to improve the bactericidal efficacy for topical application in clinics. The PDI efficacy of hydrogel was examined in vitro against the biofilms of Staphylococcus aureus (S. aureus and Pseudomonas aeruginosa (P. aeruginosa. Confocal scanning laser microscopy (CSLM was performed to investigate the penetration level of TBO into viable S. aureus biofilms. Incorporation of HMPC could increase the physicochemical properties of chitosan hydrogel including the hardness, viscosity as well as bioadhesion; however, higher HMPC concentration also resulted in reduced antimicrobial effect. CSLM analysis further demonstrated that higher HPMC concentration constrained TBO diffusion into the biofilm. The incubation of biofilm and hydrogel was further performed at an angle of 90 degrees. After light irradiation, compared to the mixture of TBO and chitosan, the hydrogel treated sample showed increased PDI efficacy indicated that incorporation of HPMC did improve antimicrobial effect. Finally, the bactericidal efficacy could be significantly augmented by prolonged retention of hydrogel in the biofilm as well as in the animal model of rat skin burn wounds after light irradiation.

  15. PHOTODYNAMIC THERAPY IN PATIENTS WITH DIFFERENT CLINICAL FORMS OF BASAL CELL CARCINOMA OF THE SKIN

    Directory of Open Access Journals (Sweden)

    O. V. Matveeva

    2014-01-01

    Full Text Available Background: Photodynamic therapy is frequently applied for non-invasive destruction of basal cell carcinomas (BCC of the skin; though, there is lack of evidence for efficacy of the method. Aim: To assess objective response of BCCs to photodynamic therapy with intralesional administration of photosensitizer Radachlorin in patients with different clinical forms, stages, flow patterns and localization of BCC. Materials and methods: 45  stage I–II BCCs patients with primary and recurrent solitary (ulcerative, superficial, scleroderma-like and nodular forms and multiple lesions (predominantly Т₁– Т₂N₀M₀, with difficult to treat localization and high risk of recurrence were included during the period from March 2004 to March 2007. All patients received one cycle of photodynamic therapy with intralesional Radachlorin (0.5–1  ml/1  cm² tumor surface and irradiation dose 300  J/cm² (wavelength 662 nm. A primary outcome measure was grade of clinical and cytological lesion regression after three months. Secondary outcome measure was stable clinical and cytological reaction at the lesion site. In the long-term, lesion recurrence was assessed yearly during 5 years. Results: Complete regression of BCCs was found in 43  (95.5% patients and 47  (95.9% lesions. In 2 (4.5% patients with partial regression of 2 (4.1% lesions repeated cycles of photodynamic therapy resulted in complete response. In BCCs Т₁N₀M₀, early outcome was independent from the clinical form of the diseases; by contrast, in BCCs Т₂N₀M₀, treatment of scleroderma-like BCCs was non-significantly less effective (66.7% compared to nodular, surface (100% for both and ulcerative (92.8% forms. In the long-term, 1  tumor recurrence was observed after 29 months at the site of completely regressed ulcerative lesion. Conclusion: Photodynamic therapy with intralesional administration of photosensitizer Radachlorin is an effective treatment method for different

  16. Overview on Topical 5-ALA Photodynamic Therapy Use for Non Melanoma Skin Cancers

    Directory of Open Access Journals (Sweden)

    Carmen Cantisani

    2014-01-01

    Full Text Available Ultraviolet radiation (UV contributes to a variety of skin diseases including inflammation, degenerative aging, and cancer. Historically, humans have been exposed to UV radiation mainly through occupational exposure; recreational UV exposure, however, has increased dramatically in recent years, because of outdoor leisure activities and to purposely tan for cosmetic purposes. Both UVB and UVA radiation have been shown to cause DNA damage and immunosuppression, the important forms of biological damage that lead to NMSC. Nonmelanoma skin cancer (NMSC is the most common malignancy, whose public health significance is often unrecognized which continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include photodynamic therapy, electrochemotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Among these, photodynamic therapy is a noninvasive technique with excellent cosmetic outcome and good curative results, when used in initial stages of skin cancers for superficial lesions. It is administered under numerous and significantly varied regimens and there are a wide range of cure rates reported, permitting treatment of large and multiple lesions with excellent cosmetic results. This is an overview of photodynamic applications especially for the treatment of NMSC, with a short focus on daylight modality.

  17. Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

    Science.gov (United States)

    Kumar, M. Suresh; Aruna, P.; Ganesan, S.

    2018-03-01

    One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

  18. Immune and antioxidizing response in cancer patients to photodynamic therapy with photohem and photosens as photosensitizers

    Science.gov (United States)

    Yakubovskaya, Raisa I.; Sokolov, Victor V.; Nemtzova, H. R.; Oganezov, Victor K.; Scherbitskaya, I. Y.; Filonenko, H. V.; Aristarkhova, E. I.; Chissov, Valery I.

    1996-01-01

    Free radicals are the main basis of anticancer effect of photodynamic therapy (PDT). At the same time, they cause different complications. The goal of this study is to investigate the changes in homeostasis of cancer patients under the influence of PDT. It was shown, as a result of study of antioxidizing and immune status of these patients, that there are significant deviations in their indices even before PDT. The treatment leads to further development of disbalance in these systems which demands correction. Several remedies have been offered for correction therapy. The application of these remedies causes the reduction of overstrain in antioxidizing defence and leads to decrease in cases of complications.

  19. Combination of ablative fractional laser and daylight-mediated photodynamic therapy for actinic keratosis in organ transplant recipients – a randomized controlled trial

    DEFF Research Database (Denmark)

    Togsverd-Bo, Katrine; Lei, Ulrikke; Erlendsson, A M

    2015-01-01

    BACKGROUND: Topical photodynamic therapy (PDT) for actinic keratoses (AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients (OTR). OBJECTIVES: We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-dPDT) compared...

  20. Efficacy of photodynamic therapy against larvae of Aedes aegypti: confocal microscopy and fluorescence-lifetime imaging

    Science.gov (United States)

    de Souza, L. M.; Pratavieira, S.; Inada, N. M.; Kurachi, C.; Corbi, J.; Guimarães, F. E. G.; Bagnato, V. S.

    2014-03-01

    Recently a few demonstration on the use of Photodynamic Reaction as possibility to eliminate larvae that transmit diseases for men has been successfully demonstrated. This promising tool cannot be vastly used due to many problems, including the lake of investigation concerning the mechanisms of larvae killing as well as security concerning the use of photosensitizers in open environment. In this study, we investigate some of the mechanisms in which porphyrin (Photogem) is incorporated on the Aedes aegypti larvae previously to illumination and killing. Larvae at second instar were exposed to the photosensitizer and after 30 minutes imaged by a confocal fluorescence microscope. It was observed the presence of photosensitizer in the gut and at the digestive tract of the larva. Fluorescence-Lifetime Imaging showed greater photosensitizer concentration in the intestinal wall of the samples, which produces a strong decrease of the Photogem fluorescence lifetime. For Photodynamic Therapy exposition to different light doses and concentrations of porphyrin were employed. Three different light sources (LED, Fluorescent lamp, Sun light) also were tested. Sun light and fluorescent lamp shows close to 100% of mortality after 24 hrs. of illumination. These results indicate the potential use of photodynamic effect against the LARVAE of Aedes aegypti.

  1. 2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: photosensitization efficiency, subcellular localization and in vivo studies.

    Science.gov (United States)

    Laranjo, Mafalda; Serra, Arménio C; Abrantes, Margarida; Piñeiro, Marta; Gonçalves, Ana C; Casalta-Lopes, João; Carvalho, Lina; Sarmento-Ribeiro, Ana B; Rocha-Gonsalves, António; Botelho, Filomena

    2013-02-01

    Photodynamic therapy (PDT) is a therapeutic modality capable of inducing cell death by oxidative stress through activation of a sensitizer by light. Aryl-porphyrin with hydroxyl groups are good photosensitizers and presence of bromine atoms can enhance the photodynamic activity through heavy atom effect. These facts and our previous work made pertinent to compare the photodynamic capacity of tetraaryl brominated porphyrin (TBr4) with the corresponding diaryl (BBr2) derivative. Cell cultures were incubated with the sensitizers, ranging from 50nM to 10μM and irradiated until 10J. Cell proliferation was analysed by MTT assay. Flow cytometry studies evaluated cell death pathways, mitochondrial membrane potential and ROS. For in vivo studies Balb/c nu/nu mice were injected with 4×10(6)cells. After PDT, monitoring was carried out for 12 days to establish Kaplan-Meier survival curves. Tumours were excised and histological analysis was performed. Both sensitizers seem to accumulate in the mitochondria. The molecules have no intrinsic cytotoxicity or in non-tumour cells at therapeutic concentrations. Both sensitizers induced a significant decrease of cell proliferation and growth of xenografts of melanoma and colorectal adenocarcinoma. Diaryl BBr2 is more efficient than tetraaryl TBr4, concerning intracellular ROS production, mitochondrial disruption and induction of cell death. The main cell death pathway is necrosis. TBr2 and BBr4 are promising sensitizers with good photodynamic properties and have the ability to induce cell death in human melanoma and colorectal adenocarcinoma in vitro and in vivo. We consider that BBr2 is a molecule that should be the subject of extensive studies towards clinical use. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Evaluation of the Combined Effects of Sonodynamic and Photodynamic Therapies in a Colon Carcinoma Tumor Model (CT26

    Directory of Open Access Journals (Sweden)

    Ameneh Sazgarnia

    2009-12-01

    Full Text Available Introduction: Photodynamic therapy is a noninvasive therapeutic method for tumors with a maximum depth of 5 mm. On the other hand, most photosensitizers are also susceptible to ultrasound waves (the basis of sonodynamic therapy. Therefore, it is expected that a combination of the two therapeutic methods will increase effectiveness of photodynamic therapies for lower doses of sensitizer and curing deeper tumors. This study evaluates the synergistic effects of photodynamic and sonodynamic therapies.     Materials and methods: The study was conducted on a colon carcinoma tumor model in Balb/c mice. The colon carcinoma tumors were induced in the mice by subcutaneous injection. Twenty four hours after intraperitoneal injection of Zinc Phthalocyanine liposome as a sensitizer, at first ultrasound irradiation with a known frequency and intensity was performed followed by illumination of the tumor area. Evaluation of the treatment efficacy was done using daily measurement of the tumors and calculation of their relative volumes. Also, all control groups were considered to confirm the effect of each therapeutic option in the study.   Results: In the first ten days post treatment, the relative volumes of all groups decreased significantly in comparison with the main control group, but the best response was observed in the photodynamic or sonodynamic therapy groups. The longest doubling time of tumor size was related to groups under photodynamic, sonodynamic and main therapies, and the shortest belonged to the control group.   Discussion and conclusion: Zinc phthalocyanine liposome is both a photosensitizer and sonsensitizer. Photodynamic and sonodynamic therapies can be efficient in retarding tumor growth rate. In this study, combination of the two methods did not cause improved therapeutic outcomes. It is predicted that this result is related to the choice of therapeutic agents and could be optimized in future.

  3. Delivering precision antimicrobial therapy through closed-loop control systems

    Science.gov (United States)

    Rawson, T M; O’Hare, D; Herrero, P; Sharma, S; Moore, L S P; de Barra, E; Roberts, J A; Gordon, A C; Hope, W; Georgiou, P; Cass, A E G; Holmes, A H

    2018-01-01

    Abstract Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients. PMID:29211877

  4. Current state and future of photodynamic therapy for the treatment of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Christina Mimikos

    2016-06-01

    Full Text Available Photodynamic therapy has shown promise in the treatment of early head and neck squamous cell carcinoma (SCC. In photodynamic therapy (PDT, a light sensitive drug (photosensitizer and visible light cause cancer cell death by the creation of singlet oxygen and free radicals, inciting an immune response, and vascular collapse. In this paper, we review several studies that demonstrate the effectiveness of PDT in the treatment of early stage SCC of the head and neck, with some showing a similar response rate to surgery. Two cases are presented to illustrate the effectiveness of PDT. Then, new advances are discussed including the discovery of STAT3 crosslinking as a potential biomarker for PDT response and interstitial PDT for locally advanced cancers. Keywords: Photodynamic therapy, PDT, Squamous cell carcinoma, Head and neck cancer

  5. Conscious sedation with inhaled 50% nitrous oxide/oxygen premix in photodynamic therapy sessions for vulvar lichen sclerosus treatment.

    Science.gov (United States)

    Cabete, Joana; Campos, Sara; Lestre, Sara

    2015-01-01

    Photodynamic therapy has been described as an effective therapeutic option in selected cases of anogenital lichen sclerosus that are refractory to first-line treatments. However, procedure-related pain is a limiting factor in patient adherence to treatment. The authors report the case of a 75-year-old woman with highly symptomatic vulvar lichen sclerosus, successfully treated with photodynamic therapy. An inhaled 50% nitrous oxide/oxygen premix was administered during sessions, producing a pain-relieving, anxiolytic, and sedative effect without loss of consciousness. This ready-to-use gas mixture may be a well-tolerated and accepted alternative to classical anesthetics in Photodynamic therapy, facilitating patients' adherence to illumination of pain-prone areas.

  6. "Smart" nickel oxide based core-shell nanoparticles for combined chemo and photodynamic cancer therapy.

    Science.gov (United States)

    Bano, Shazia; Nazir, Samina; Munir, Saeeda; AlAjmi, Mohamed Fahad; Afzal, Muhammad; Mazhar, Kehkashan

    2016-01-01

    We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy.

  7. Combination photodynamic therapy of human breast cancer using salicylic acid and methylene blue

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh; Jahanshiri, Maryam

    2017-09-01

    The objective of this study was to evaluate the effects of combination therapy with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid (SA) as chemo-therapy anticancer agent. The binding of salicylic acid to methylene blue was studied using spectrophotometric method. The results show the 1:2 complex formation between SA and MB. The binding constants and related Gibbs free energies o are obtained (Kb1 = 183.74, Kb2 = 38.13 and ∆ Gb1° = 12.92 kJ·mol- 1, ∆ Gb2° =9.02 kJ·mol- 1). The spectrophotometric results show the improvement in solubilization and reduction prevention for SA and MB in the complex form. These results are in agreements with cellular experiments. The dark toxicity measurements represent the improve efficacy of chemotherapy using combination of SA and MB. The photodynamic therapy results (using red LED as light source (630 nm; power density: 30 mW cm- 2)) show that the cancer cell killing efficiency of MB increases in the combination with SA due to reduction prevention and stabilization of monomeric form of MB.

  8. In vitro evaluation of Radachlorin sensitizer for photodynamic therapy.

    Science.gov (United States)

    Douillard, Samuel; Lhommeau, Isabelle; Olivier, David; Patrice, Thierry

    2010-02-12

    This paper reports the evaluation of a new photosensitizer, Radachlorin in comparison with one of its well known components but used solely, Chlorin e(6). The photodynamic properties and cell uptake and localisation of the two drugs were compared. In vitro studies were conducted on human adenocarcinoma cells (HT29) and lung carcinoma cell line (A549). Both dyes showed an absorption maximum between 640 and 650 nm, but those absorption peaks are enhanced by interactions with serum, with a shifted maximum at 661 and 664 nm, and much higher absorbance. As Radachlorin is constituted of different products and as photoreactivity is dependent on absorbed light energy, we chose to adapt concentrations so that both drugs had the same absorption at the irradiation wavelength (664 nm) for photoreactivity tests, and express concentrations in optical density at 664 nm. The capacity of the two drugs to generate Reactive Oxygen Species was identical, but on HT29 cells, Radachlorin reaches its optimal LD50 sooner than Chlorin e(6). Radachlorin LD50 on HT29 cells was 0.0251 OD(664 nm) after 2 h and 0.0672 OD(664 nm) for Chlorin e(6) for a 20 J cm(-2) irradiation. Radachlorin gave very similar results on A549 cells, LD50 being 0.05 for 5 J irradiation, and 0.026 for 10 and 20 J cm(-2). Pharmacokinetics using fluorescence showed that, even if Radachlorin quickly crossed HT29 (a human colonic cancer line) cell membrane, cellular distribution evolved from a diffuse cytoplasmic repartition 1 hour after Radachlorin addition to a delimited localisation into organelles all around the nucleus. Radachlorin intracellular fluorescence decreased after 4 h, whereas we did not observe a decrease of Chlorin e(6) intracellular fluorescence for times up to 24 h. In both case, a quick decline was observed as soon as the culture medium was replaced with a drug-free one. Radachlorin appears to be an excellent photosensitizer, with similar phototoxicity to Chlorin e(6) on cell cultures, but with quicker

  9. SU-E-T-191: First Principle Calculation of Quantum Yield in Photodynamic Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abolfath, R; Guo, F; Chen, Z; Nath, R [Yale New Haven Hospital, New Haven, CT (United States)

    2014-06-01

    Purpose: We present a first-principle method to calculate the spin transfer efficiency in oxygen induced by any photon fields especially in MeV energy range. The optical pumping is mediated through photosensitizers, e.g., porphyrin and/or ensemble of quantum dots. Methods: Under normal conditions, oxygen molecules are in the relatively non-reactive triplet state. In the presence of certain photosensitizer compounds such as porphyrins, electromagnetic radiation of specific wavelengths can excite oxygen to highly reactive singlet state. With selective uptake of photosensitizers by certain malignant cells, photon irradiation of phosensitized tumors can lead to selective killing of cancer cells. This is the basis of photodynamic therapy (PDT). Despite several attempts, PDT has not been clinically successful except in limited superficial cancers. Many parameters such as photon energy, conjugation with quantum dots etc. can be potentially combined with PDT in order to extend the role of PDT in cancer management. The key quantity for this optimization is the spin transfer efficiency in oxygen by any photon field. The first principle calculation model presented here, is an attempt to fill this need. We employ stochastic density matrix description of the quantum jumps and the rate equation methods in quantum optics based on Markov/Poisson processes and calculate time evolution of the population of the optically pumped singlet oxygen. Results: The results demonstrate the feasibility of our model in showing the dependence of the optical yield in generating spin-singlet oxygen on the experimental conditions. The adjustable variables can be tuned to maximize the population of the singlet oxygen hence the efficacy of the photodynamic therapy. Conclusion: The present model can be employed to fit and analyze the experimental data and possibly to assist researchers in optimizing the experimental conditions in photodynamic therapy.

  10. The efficacy of photodynamic therapy for basal cell carcinoma with intralesional injection of radachlorine

    Directory of Open Access Journals (Sweden)

    T. E. Sukhova

    2015-01-01

    Full Text Available The results of evaluation of the efficiency of photodynamic therapy with photosensitizer radachlorine for basal cell carcinoma are represented. The study included patients with primary and recurrent cancer, solitary and multiple foci of different histological subtypes. All tumors corresponded stages T1-2N0M0. The radachlorine solution was injected into pathological focus at dose of 1.75-3.50 mg/ cm2 of tumor 15 min before the onset of irradiation (wavelength of 662 nm, light dose of 300 J/cm2. The evaluation of efficiency by means of short-term and long-term outcomes was performed on the basis of clinical and cytological data. According to shortterm outcomes evaluation, the total tumor regression was in 43 (95,5% patients for 47 (95,9% tumors. The partial regression was achieved in 2 (4,5% patients, who subsequently had one repeated course of photodynamic therapy with short-term outcome as total tumor regression. All patients with multiple, superficial and nodal forms of basal cell carcinoma had total tumor regression in 100% of cases, with ulcerated form – in 94,4%, with morphea-like form – in 83,3%. During follow-up in subjects, 44 (97,7% patients had 5-year recurrence-free period. The relapse of tumor was detected in 1 (2,3% patient after PDT for primary cancer of nasal ala stage Т2N0M0 of solid and adenoid histological subtype. Thus, photodynamic therapy with intralesional injection of radachlorine showed high efficiency for treating all existent clinical forms and histological subtypes of basal cell carcinoma. 

  11. A laser-spectroscopy complex for fluorescent diagnostics and photodynamic therapy of age-related macula degeneration

    Science.gov (United States)

    Shevchik, S. A.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Kharnas, Sergey S.; Loschenov, Victor B.

    2004-06-01

    A laser-spectroscopy complex was developed for fluorescent diagnostics and photodynamic therapy of age related macula degeneration using the Russian photosensitizer Photosense. The complex is based on slit lamp which was additionally equipped with an optical adapter, and the video adapter allows to combine the procedure of photodynamic therapy and the control of its carrying in the frame work of one procedure. The sensitivity and spatial resolution of the complex were investigated using a special test object. The availability of the developed complex and Photosense itself was examined on experimental animals.

  12. Temoporfin-loaded 1-tetradecanol-based thermoresponsive solid lipid nanoparticles for photodynamic therapy

    Czech Academy of Sciences Publication Activity Database

    Brezaniova, I.; Hrubý, Martin; Králová, Jarmila; Král, V.; Černochová, Zulfiya; Černoch, Peter; Šlouf, Miroslav; Kredatusová, Jana; Štěpánek, Petr

    2016-01-01

    Roč. 241, 10 November (2016), s. 34-44 ISSN 0168-3659 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109; GA TA ČR(CZ) TE01020118; GA MŠk(CZ) LO1507; GA MŠk(CZ) 7F14009 Institutional support: RVO:61389013 ; RVO:68378050 Keywords : photodynamic therapy * nanomedicine * drug delivery Subject RIV: CD - Macromolecular Chemistry; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 7.786, year: 2016

  13. Prospects of radical-interacting porphyrin photosensitizers and their possible use in photodynamic therapy

    Science.gov (United States)

    Gal, Dezso; Shuliakovskaya, T.; Vidoczy, Tamas; Elzemzam, Saleh; Vasvari, Gabor; Suemegi, L.; Kuti, Zsolt

    1994-03-01

    Based on literature data obtained in various fields with respect to studies on the role of free radicals in biology and on the kinetics of triplet-doublet interactions, it is suggested that excited photosensitizers react in vivo with free radicals formed in malignant tissues during photodynamic therapy (PDT) and this interaction competes with sensitizer-radical + molecule and the singlet oxygen mediated effects. Experimental results by laser flash photolysis and electron spin resonance revealed that sensitizer applied in PDT react with stable free radicals presumably both by energy transfer and electron transfer.

  14. [Photochemical internalisation (PCI): a further development of photodynamic therapy for the treatment of skin cancer].

    Science.gov (United States)

    Johansen, Pål; Berg, K; Selbo, P K; Hofbauer, G F L

    2010-11-17

    Recently, several new and non-invasive methods have been introduced for the treatment of skin cancers. Topical creams using the immune modulator imiquimod or the COX inhibitor diclofenac (with hyaluronic acid) are now registered for use against neoplasms such as basal or squamous cell carcinoma. Another modern treatment option is photodynamic therapy (PDT). A refined version of PDT, namely photochemical internalisation, is currently subject to a first clinical trial in patients with osteosarcoma, squamous cell carcinoma, head and neck cancer as well as adenocarcinoma of the breast. Preliminary results from this trial suggest that PCI seems to be a promising treatment.

  15. Influence of the Human Skin Tumor Type in Photodynamic Therapy Analysed by a Predictive Model

    Directory of Open Access Journals (Sweden)

    I. Salas-García

    2012-01-01

    Full Text Available Photodynamic Therapy (PDT modeling allows the prediction of the treatment results depending on the lesion properties, the photosensitizer distribution, or the optical source characteristics. We employ a predictive PDT model and apply it to different skin tumors. It takes into account optical radiation distribution, a nonhomogeneous topical photosensitizer spatial temporal distribution, and the time-dependent photochemical interaction. The predicted singlet oxygen molecular concentrations with varying optical irradiance are compared and could be directly related with the necrosis area. The results show a strong dependence on the particular lesion. This suggests the need to design optimal PDT treatment protocols adapted to the specific patient and lesion.

  16. Effect of molecular surrounding to spectral characteristics of chlorophylls - the perspective photodynamic therapy photosensitizers

    International Nuclear Information System (INIS)

    Zakhidov, E. A.; Kokhkharov, A. M.; Nematov, Sh. Q.

    2011-01-01

    In the paper the absorption and fluorescence spectra of biomolecules of natural origin a chlorophyll and bacteriochlorophyll have been analysed. The possibility of gigantic (up to several thousand sm -1 ) frequency shifts of the maxima of absorption and fluorescence bands of these molecules depending on physical characteristics their molecular surrounding is shown. Expressions describing dependence of the frequency shift from electron polarizability and ionization potentials of the molecules are discussed. The molecules studied are considered as effective photosensitizers for photodynamic therapy in long wavelength range of the spectra. (authors)

  17. Increased protoporphyrin IX accumulation does not improve the effect of photodynamic therapy for actinic keratosis

    DEFF Research Database (Denmark)

    Nissen, C V; Heerfordt, I M; Wiegell, S R

    2017-01-01

    BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is highly effective for treating actinic keratosis (AK) on the face/scalp, but less effective on the extremities. Insufficient accumulation of protoporphyrin IX (PpIX) may cause these inferior efficacy rates. However...... (P = 0·001 and P = 0·002, respectively). However, the median total clearance rates did not improve accordingly: 3hC+ (55·0%), 21hC- (55·0%) and 21hC+ (53·6%). Conversely, insufficient PpIX accumulation in the 3hC- regimen led to a significantly lower clearance rate (33·3%) than the other regimens (P...

  18. Light-Emitting Diode-Based Illumination System for In Vitro Photodynamic Therapy

    OpenAIRE

    Defu Chen; Huifen Zheng; Zhiyong Huang; Huiyun Lin; Zhidong Ke; Shusen Xie; Buhong Li

    2012-01-01

    The aim of this study is to develop a light-emitting diode- (LED-) based illumination system that can be used as an alternative light source for in vitro photodynamic therapy (PDT). This illumination system includes a red LED array composed of 70 LEDs centered at 643 nm, an air-cooling unit, and a specific-designed case. The irradiance as a function of the irradiation distance between the LED array and the sample, the homogeneity and stability of irradiation, and the effect of long-time irrad...

  19. The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances

    International Nuclear Information System (INIS)

    Zawacka-Pankau, Joanna; Krachulec, Justyna; Grulkowski, Ireneusz; Bielawski, Krzysztof P.; Selivanova, Galina

    2008-01-01

    Photodynamic therapy (PDT) is a promising modality for the treatment of both pre-malignant and malignant lesions. The mechanism of action converges mainly on the generation of reactive oxygen species which damage cancer cells directly as well as indirectly acting on tumor vasculature. The exact mechanism of PDT action is not fully understood, which is a formidable barrier to its successful clinical application. Elucidation of the mechanisms of cancer cell elimination by PDT might help in establishing highly specific, non-genotoxic anti-cancer treatment of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor p53 protein recognized as the guardian of the genome. Together with its family members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress stimuli. The wild-type and mutant p53-targeting chemotherapeutics are currently extensively investigated as a promising strategy for highly specific anti-cancer therapy. In photodynamic therapy porphyrinogenic sensitizers are the most widely used compounds due to their potent biophysical and biochemical properties. Recent data suggest that the p53 tumor suppressor protein might play a significant role in porphyrin-PDT-mediated cell death by direct interaction with the drug which leads to its accumulation and induction of p53-dependent cell death both in the dark and upon irradiation. In this review we describe the available evidence on the role of p53 in PDT

  20. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

    Science.gov (United States)

    Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

    2010-01-25

    Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

    Science.gov (United States)

    Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

    2010-12-01

    A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area.

  2. pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy.

    Science.gov (United States)

    Tang, Xiang-Long; Jing, Feng; Lin, Ben-Lan; Cui, Sheng; Yu, Ru-Tong; Shen, Xiao-Dong; Wang, Ting-Wei

    2018-05-02

    By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe 3 O 4 @mSiO 2 (DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe 3 O 4 @mSiO 2 (DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

  3. The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

    Directory of Open Access Journals (Sweden)

    Shi J

    2013-07-01

    Full Text Available Jinjin Shi,* Rourou Ma,* Lei Wang, Jing Zhang, Ruiyuan Liu, Lulu Li, Yan Liu, Lin Hou, Xiaoyuan Yu, Jun Gao, Zhenzhong Zhang School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, People's Republic of China*These authors contributed equally to this workAbstract: Carbon nanotubes (CNTs have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME, was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy.Keywords: photodynamic therapy, photothermal therapy, HA-derivatized carbon nanotubes, tumor targeting, synergistic effect, hematoporphyrin monomethyl ether

  4. Virus Capsids as Targeted Nanoscale Delivery Vessels of Photoactive Compounds for Site-Specific Photodynamic Therapy

    Science.gov (United States)

    Cohen, Brian A.

    The research presented in this work details the use of a viral capsid as an addressable delivery vessel of photoactive compounds for use in photodynamic therapy. Photodynamic therapy is a treatment that involves the interaction of light with a photosensitizing molecule to create singlet oxygen, a reactive oxygen species. Overproduction of singlet oxygen in cells can cause oxidative damage leading to cytotoxicity and eventually cell death. Challenges with the current generation of FDA-approved photosensitizers for photodynamic therapy primarily stem from their lack of tissue specificity. This work describes the packaging of photoactive cationic porphyrins inside the MS2 bacteriophage capsid, followed by external modification of the capsid with cancer cell-targeting G-quadruplex DNA aptamers to generate a tumor-specific photosensitizing agent. First, a cationic porphyrin is loaded into the capsids via nucleotide-driven packaging, a process that involves charge interaction between the porphyrin and the RNA inside the capsid. Results show that over 250 porphyrin molecules associate with the RNA within each MS2 capsid. Removal of RNA from the capsid severely inhibits the packaging of the cationic porphyrins. Porphyrin-virus constructs were then shown to photogenerate singlet oxygen, and cytotoxicity in non-targeted photodynamic treatment experiments. Next, each porphyrin-loaded capsid is externally modified with approximately 60 targeting DNA aptamers by employing a heterobifunctional crosslinking agent. The targeting aptamer is known to bind the protein nucleolin, a ubiquitous protein that is overexpressed on the cell surface by many cancer cell types. MCF-7 human breast carcinoma cells and MCF-10A human mammary epithelial cells were selected as an in vitro model for breast cancer and normal tissue, respectively. Fluorescently tagged virus-aptamer constructs are shown to selectively target MCF-7 cells versus MCF-10A cells. Finally, results are shown in which porphyrin

  5. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Narsireddy A

    2015-11-01

    Full Text Available Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao21CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, IndiaAbstract: Challenges in photodynamic therapy (PDT include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl-21H,23H-porphine [PS] and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine dendrimer (G4 was conjugated with a PS and a nitrilotriacetic acid (NTA group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.Keywords: photodynamic therapy, dendrimers, nanoparticle, targeted delivery, Affibody, xenograft animal model

  6. [Physical treatment methods for acne. Light, laser, photodynamic therapy and peeling].

    Science.gov (United States)

    Borelli, C; Korting, H C

    2010-02-01

    The medical treatment of acne is generally sufficient to meet the expectations of acne patients. However, in a number of situations additional therapeutic approaches may be advisable. There are a wide variety of useful physical methods. They range from electromagnetic waves, usually light, to peeling and manual therapy. Phototherapy of acne includes not just visible light but also laser and flash lamp therapy. The present review provides an overview on the evidence. Visible light, in particular blue light, provides an effective option for treatment of inflammatory acne. Photodynamic therapy also is efficacious; however, it should not be used because of an unfavorable risk-benefit ratio. UV treatment of acne is obsolete. Newer studies on the use of a variety of laser systems and flash lamps have demonstrated in part rewarding results.

  7. NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles

    Science.gov (United States)

    Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

    2014-09-01

    The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.

  8. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

    Directory of Open Access Journals (Sweden)

    Giovana Maria Fioramonti Calixto

    2016-03-01

    Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  9. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

    Science.gov (United States)

    Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

    2016-03-11

    Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  10. Regulation of porphyrin synthesis and photodynamic therapy in heavy metal intoxication.

    Science.gov (United States)

    Grinblat, Borislava; Pour, Nir; Malik, Zvi

    2006-01-01

    Protoporphyrin IX (PpIX) synthesis by malignant cells is successfully exploited for photodynamic therapy (PDT) following administration of 5-aminolevulinic acid (ALA) and light irradiation. The influence of two environmental heavy metal poisons, lead and gallium, on PpIX-synthesis and ALA-PDT was studied in two neu-ronal cell lines, SH-SY5Y neuroblastoma and PC12 pheochromocytoma. The heavy metal intoxication affected two of the heme-synthesis enzymes, ALA-dehydratase (ALAD) and porphobilinogen deaminase (PBGD). The present results show that lead poisoning significantly decreased the PBGD cellular level and inhibited its enzymatic activity, whereas the effects of gallium were less prominent. Although, the protein levels were reduced, the mRNA levels of PBGD remained unchanged during metal intoxication. These findings show additional inhibitory activity of lead on top of its classical effect on ALAD. Proteasome activity was enhanced during lead treatment, as measured by the AMC fluorigenic proteasome assay. The reduction in PBGD levels was not a consequence of PBGD mRNA reduced synthesis, which remained unchanged as shown by RT-PCR analysis. As a result of the lead poisoning, marked alterations in the cell cycle were observed, including a decreased G1 phase and an increased number of S phase cells. The efficacy of ALA-PDT was reduced in correlation with decreased activities of the enzymes during lead intoxication. We may conclude that lead poisoning adversely affects the outcome of ALA photodynamic therapy of cancer.

  11. Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

    Science.gov (United States)

    Li, Jian-Wei; Wu, Zhong-Ming; Magetic, Davor; Zhang, Li-Jun; Chen, Zhi-Long

    2015-12-01

    In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

  12. Photodynamic therapy versus ultrasonic irrigation: interaction with endodontic microbial biofilm, an ex vivo study.

    Science.gov (United States)

    Muhammad, Omid H; Chevalier, Marlene; Rocca, Jean-Paul; Brulat-Bouchard, Nathalie; Medioni, Etienne

    2014-06-01

    Photodynamic therapy was introduced as an adjuvant to conventional chemo-mechanical debridement during endodontic treatment to overcome the persistence of biofilms. The aim of this study was to evaluate the ability of photodynamic therapy (PDT) to disrupt an experimental microbial biofilm inside the root canal in a clinically applicable working time. Thirty extracted teeth were prepared and then divided in three groups. All samples were infected with an artificially formed biofilm made of Enterococcus faecalis, Streptococcus salivarius, Porphyromonas gingivalis and Prevotella intermedia bacteria. First group was treated with Aseptim Plus® photo-activated (LED) disinfection system, second group by a 650 nm Diode Laser and Toluidine blue as photosensitizer, and the third group, as control group, by ultrasonic irrigation (PUI) using EDTA 17% and NaOCl 2.6% solutions. The working time for all three groups was fixed at 3 min. Presence or absence of biofilm was assessed by aerobic and anaerobic cultures. There was no statistically significant difference between results obtained from groups treated by Aseptim Plus® and Diode Laser (Pirrigation and NaOCl and EDTA solutions had the best results (Pendodontic artificial microbial biofilm and could not inhibit bacterial growth in a clinically favorable working time. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. PHOTODYNAMIC THERAPY FOR HEAD AND NECK BASAL CELL SKIN CANCER WITH ADDITIONAL INTERSTITIAL LASER IRRADIATION

    Directory of Open Access Journals (Sweden)

    V. N. Kapinus

    2017-01-01

    Full Text Available The article is devoted to the development and evaluation of the effi ciency of photodynamic therapy (PDT with photosensitizer photolon with additional interstitial laser irradiation in patients with head and  neck basal cell skin cancer (BCSC. Treatment was performed in 55  patients. On the fi rst stage, all patients underwent photodynamic  therapy with interstitial irradiation using fl exible optical fi bers with  cylindrical diffuser, on the second stage PDT with distant delivery of  laser at a dose of 50-300 J/cm2 was carried out. During the follow- up period of 6 months to 4 years in 13 (23.6% of the 55 patients a  recurrence of the disease was diagnosed. A higher rate of recurrence was in the group of patients who underwent PDT for recurrent  neoplasms compared with patients with primary disease (37.5% and 4.3%, respectively, in patients with endophytic growth of the tumor compared to patients with exophytic component (30.0% and 16.0%,respectively and in patients with large tumors (up to 2.0 cm – 14.3%, from 2.0 to 5.0 cm – 16.7% and more than 5.0 cm – 54.4%.

  14. Use of photodynamic therapy in the treatment of bovine subclinical mastitis.

    Science.gov (United States)

    Moreira, Lívia Helena; de Souza, José Carlos Pereira; de Lima, Carlos José; Salgado, Miguel Angel Castillo; Fernandes, Adriana Barrinha; Andreani, Dora Inés Kozusny; Villaverde, Antonio Balbin; Zângaro, Renato Amaro

    2018-03-01

    Bovine mastitis is a disease that causes a severe drawback in dairy production. Conventional treatments with antibiotic could leave antibiotic residues in the milk. The aim of this study was to evaluate the effect of photodynamic therapy in the treatment of bovine subclinical mastitis to develop an in vivo therapeutic protocol that could be used in routine farm practice, favoring the early return to production. Forty cows with subclinical mastitis (n = 40) were divided into 4 groups (control, photodynamic therapy - PDT, light irradiation - LED, and photosensitizer - PS). Control group received no treatment, PDT group received application of 1.0 mL of 2.5% toluidine blue photosensitizer followed by LED irradiation at λ = 635 nm, the LED group was treated with LED irradiation alone, and the PS group received only 2.5% toluidine blue dye. LED irradiation was applied to the mammary gland by means of an acrylic light guide coupled to the LED equipment. The PDT and LED groups were irradiated with 200 J/cm 2 at three different positions inside the mammary gland. Milk samples were collected at 0 h, 12 h, 24 h after treatment for microbial identification and total bacterial count. The treatment of the PDT group showed significant difference p bovine mastitis. There was no need to separate the animal from production. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. MS2 bacteriophage as a delivery vessel of porphyrins for photodynamic therapy

    Science.gov (United States)

    Cohen, Brian A.; Kaloyeros, Alain E.; Bergkvist, Magnus

    2011-02-01

    Challenges associated with photodynamic therapy (PDT) include the packaging and site-specific delivery of therapeutic agents to the tissue of interest. Nanoscale encapsulation of PDT agents inside targeted virus capsids is a novel concept for packaging and site-specific targeting. The icosahedral MS2 bacteriophage is one potential candidate for such a packaging-system. MS2 has a porous capsid with an exterior diameter of ~28 nm where the pores allow small molecules access to the capsid interior. Furthermore, MS2 presents suitable residues on the exterior capsid for conjugation of targeting ligands. Initial work by the present investigators has successfully demonstrated RNA-based self-packaging of a heterocyclic PDT agent (meso-tetrakis(para-N-trimethylanilinium)porphine, TMAP) into the MS2 capsid. Packaging photoactive compounds in confined spaces could result in energy transfer between the molecules upon photoactivation, which could in turn reduce the production of radical oxygen species (ROS). ROS are key components in photodynamic therapy, and a reduced production could negatively impact the efficacy of PDT treatment. Here, findings are presented from an investigation of ROS generation of TMAP encapsulated within the MS2 capsid compared to free TMAP in solution. Monitoring of ROS production upon photoactivation via a specific singlet oxygen assay revealed the impact on ROS generation between packaged porphyrins as compared to free porphyrin in an aqueous solution. Follow on work will study the ability of MS2-packaged porphyrins to generate ROS in vitro and subsequent cytotoxic effects on cells in culture.

  16. Effectiveness of erythrosine-mediated photodynamic antimicrobial chemotherapy on dental plaque aerobic microorganisms: A randomized controlled trial.

    Science.gov (United States)

    Bhat, Manohar; Acharya, Swathi; Prasad, Kakarla Veera Venkata; Kulkarni, Raghavendra; Bhat, Anithraj; Bhat, Devikripa

    2017-01-01

    Dental plaque is one of the predominant causes of major oral diseases. Although mechanical and chemical methods are extensively followed to control the development of plaque, plaque-related diseases still persist. Therefore, this necessitates for alternative measures of plaque control, one such alternative is photodynamic antimicrobial chemotherapy (PACT). Split mouth randomized clinical trial (CTRI/2017/03/008239) was conducted on 30 participants who reported to the hospital. Participants were asked to rinse their mouth for 1 min using 10 ml of 25 μM erythrosine solutions. Same tooth on both quadrants of the same jaw are selected as the test and control. Intervention used was halogen-based composite curing light with wavelength of 500-590 nm. Plaque sample from the control tooth and test tooth was collected before and after exposure, respectively, and sent to microbiological laboratory for colony count. Logarithmic mean and standard deviation of control group with 10 2 dilutions of aerobic microbial count were found to be 5.34 ± 0.94, and for experimental group, it was 4.47 ± 1.37. The statistical difference between mean CFU values between aerobic bacterial counts was significant ( P = 0.006). Erythrosine-mediated PACT reduces the extent of dental plaque microbial count and has a potential preventive and therapeutic use in day-to-day life and dental clinics.

  17. Combination therapy of low-fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane in choroidal osteoma

    Directory of Open Access Journals (Sweden)

    Rodney J Morris

    2011-01-01

    Full Text Available Choroidal osteoma is an unusual form of intraocular calcification seen in otherwise healthy eyes. It is a benign idiopathic osseous tumor of the choroid, typically seen in young females. Choroidal neovascular membrane (CNVM is a complication seen in one-third of these patients and carries a poor visual outcome. We report a case of a 25-year-old hyperthyroid female with choroidal osteoma and subfoveal CNVM in her left eye which was successfully treated using low-fluence photodynamic therapy (PDT with verteporfin followed by a single injection of intravitreal ranibizumab.

  18. "Smart" nickel oxide based core–shell nanoparticles for combined chemo and photodynamic cancer therapy

    Directory of Open Access Journals (Sweden)

    Bano S

    2016-07-01

    Full Text Available Shazia Bano,1–3,* Samina Nazir,2,* Saeeda Munir,3 Mohamed Fahad AlAjmi,4 Muhammad Afzal,1 Kehkashan Mazhar3 1Department of Physics, The Islamia University of Bahawalpur, 2Nanosciences and Technology Department, National Centre for Physics, Islamabad, 3Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan; 4College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia *These authors contributed equally to this work Abstract: We report “smart” nickel oxide nanoparticles (NOPs as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA connected bovine serum albumin (BSA shell on entrapped doxorubicin (DOX. The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm2, at pH=5.5. The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy. Keywords: light-triggered drug release, cancer, bovine serum albumin, multi-model therapy

  19. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer

    NARCIS (Netherlands)

    Van Driel, Pieter B A A; Boonstra, Martin C.; Slooter, Maxime D.; Heukers, Raimond; Stammes, Marieke A.; Snoeks, Thomas J A; De Bruijn, Henriette S.; Van Diest, Paul J.; Vahrmeijer, Alexander L.; Van Bergen En Henegouwen, Paul M P; Van De Velde, Cornelis J H; Löwik, Clemens W G M; Robinson, Dominic J.; Oliveira, Sabrina

    2016-01-01

    Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has

  20. Efficiency of Photodynamic Therapy in the Treatment of Diffuse Facial Viral Warts in an Immunosuppressed Patient: Towards a Gold Standard

    Directory of Open Access Journals (Sweden)

    M. Caucanas

    2010-12-01

    Full Text Available A 64-year-old man with a pulmonary transplant developed diffuse verrucae vulgares of the neck. After the failure of multiple cryotherapy treatments, 3 sessions of photodynamic therapy resulted in rapid therapeutic clinical success. This moderately painful and well-tolerated treatment is reproducible and can be very useful in treating papillomavirus infections in the immunosuppressed patient.

  1. Pretreatment with 5-Fluorouracil Cream Enhances the Efficacy of Daylight-mediated Photodynamic Therapy for Actinic Keratosis

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Heerfordt, Ida Marie; Wiegell, Stine R

    2017-01-01

    The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized intra...

  2. Increase in protoporphyrin IX after 5-aminolevulinic acid based photodynamic therapy is due to local re-synthesis

    NARCIS (Netherlands)

    de Bruijn, Henriëtte S.; Kruijt, Bastiaan; van der Ploeg-van den Heuvel, Angélique; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.

    2007-01-01

    Protoporphyrin IX (PpIX) fluorescence that is bleached during aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) increases again in time after treatment. In the present study we investigated if this increase in PpIX fluorescence after illumination is the result of local re-synthesis or of

  3. Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis

    NARCIS (Netherlands)

    Gomi, Harumi; Solomkin, Joseph S.; Schlossberg, David; Okamoto, Kohji; Takada, Tadahiro; Strasberg, Steven M.; Ukai, Tomohiko; Endo, Itaru; Iwashita, Yukio; Hibi, Taizo; Pitt, Henry A.; Matsunaga, Naohisa; Takamori, Yoriyuki; Umezawa, Akiko; Asai, Koji; Suzuki, Kenji; Han, Ho-Seong; Hwang, Tsann-Long; Mori, Yasuhisa; Yoon, Yoo-Seok; Huang, Wayne Shih-Wei; Belli, Giulio; Dervenis, Christos; Yokoe, Masamichi; Kiriyama, Seiki; Itoi, Takao; Jagannath, Palepu; Garden, O. James; Miura, Fumihiko; de Santibañes, Eduardo; Shikata, Satoru; Noguchi, Yoshinori; Wada, Keita; Honda, Goro; Supe, Avinash Nivritti; Yoshida, Masahiro; Mayumi, Toshihiko; Gouma, Dirk J.; Deziel, Daniel J.; Liau, Kui-Hin; Chen, Miin-Fu; Liu, Keng-Hao; Su, Cheng-Hsi; Chan, Angus C. W.; Yoon, Dong-Sup; Choi, In-Seok; Jonas, Eduard; Chen, Xiao-Ping; Fan, Sheung Tat; Ker, Chen-Guo; Giménez, Mariano Eduardo; Kitano, Seigo; Inomata, Masafumi; Mukai, Shuntaro; Higuchi, Ryota; Hirata, Koichi; Inui, Kazuo; Sumiyama, Yoshinobu; Yamamoto, Masakazu

    2018-01-01

    Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community-acquired and healthcare-associated infections. The listed agents are for

  4. Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach.

    Science.gov (United States)

    Lee, Tae Yoon; Cheon, Young Koog; Shim, Chan Sup

    2016-04-01

    This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p hilar CC. Lower pre-PDT bilirubin levels were associated with longer survival in all patients.

  5. Photodynamic therapy for mycosis fungoides: a case series and review of the literature

    Directory of Open Access Journals (Sweden)

    Robert E. Hunger

    2015-01-01

    Full Text Available Mycosis fungoides (MF is the most common form of cutaneous T cell lymphoma. In early stages of the disease, topical therapeutic approaches like steroids, chemotherapy, phototherapy or spot radiation therapy are most commonly used. Photodynamic therapy (PDT is widely executed in the treatment of actinic keratosis and superficial basal cell carcinoma. The effective use of PDT for early forms of MF has been previously demonstrated in a series of cases. In this instance, the treatment of MF (n = 6, 11 lesions with methyl alanine PDT (MAL-PDT in 73% of the treated lesions showed a complete response. Within the timeframe of 25-51 months, no recurrence of the successfully treated lesions was observed, on the contrary some of the patients developed new lesions on different sites. Hence, this case study shows that patients having a single or few MF lesions can be successfully treated by PDT.

  6. A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

    Science.gov (United States)

    Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

    2014-04-01

    The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

  7. A Florescence Detection Module for Photodynamic Therapy Optimization by Measuring the Concentration of Photo sensitizer

    International Nuclear Information System (INIS)

    Serrano Navarro, Joel; Stolik Isakina, Suren; La Rosa Vazquez, Jose M. de; Valor Reed, Alma

    2016-01-01

    In the present work, a portable fluorescence detection system designed and built for dosimetry control applications in Photodynamic Therapy is presented. The system excites the used photo sensitizer drug with a modulated laser light source and subsequently measures the radiance of the emitted fluorescent light. Since the fluorescent radiance is directly related to the photosensitizers concentration, this measurement allows for real-time monitoring of the photo sensitizer concentration in the treated tissue. The system is thought to permit adjusting the therapeutic regime in order to optimize the expected therapy results. In the developed system, a synchronous detection technique is employed to recover the fluorescence signals embedded in noisy backgrounds and lit environments. A scanning probe with a 405 nm diode laser is used to excite the photo sensitizer, while a detection wavelength range from 590 nm to 700 nm has been implemented. (Author)

  8. The treatment of larynxpapillomas with the aid of photodynamic therapy

    International Nuclear Information System (INIS)

    Feyh, H.

    1992-01-01

    HPV associated papillomas are the most common benign laryngeal tumors in children and show similar distribution to both sexes. Papilloma and condyloma are caused by the human papilloma virus (HPV) belonging to the family of papovaviruses. Numerous studies have shown that there are at least 16 HPV subspecies apparent in man causing different diseases. In children larynx papillomas are histologically benign whereas in adults papillomatosis turns into cancer in 20% of the cases. Conventional therapy is based on a surgical removal of the papillomas by means of carbondiogsite laser systems. Because of the recurrent character of this disorder the increasing number of surgical interventions leave scars in the mucous membranes of the vocal cords of the larynx. This results in increasing malfunctioning of the larynx. All other treatment agents that have been added to surgery like steroids, aureomycine, Idoxoridine, Podophyllin, Vaccine and Interferon showed no significant effect to prolonge the treatment interval for the recurrent larynx papillomatosis. As a new treatment modality PDT confirmed to be a functional therapeutic agent for recurrent laryngeal papillomas. (author). 12 refs

  9. Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions.

    Science.gov (United States)

    McCarron, Paul A; Donnelly, Ryan F; Zawislak, Agnieszka; Woolfson, A David; Price, John H; McClelland, Raymond

    2005-04-11

    An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 Ncm(-2). Patient evaluation demonstrated comfort and firm attachment for up to 4h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

  10. Bovine serum albumin nanoparticles loaded with Photosens photosensitizer for effective photodynamic therapy

    Science.gov (United States)

    Khanadeev, Vitaly; Khlebtsov, Boris; Packirisamy, Gopinath; Khlebtsov, Nikolai

    2017-03-01

    Polymeric nanoparticles (NPs) are widely used for drug delivery applications due to high biodegradability, low toxicity and high loading capacity. The focus of this study is the development of photosensitizer Photosens (PS) loaded albumin NPs for efficient photodynamic therapy (PDT). To fabricate PS-loaded bovine serum albumin nanoparticles (BSA-PS NPs), we used a coacervation method with glutaraldehyde followed by passive loading of PS. Successful loading of PS was confirmed by appearance of characteristic peak in absorption spectrum which allows to determine the PS loading in BSA NPs. The synthesized BSA-PS NPs demonstrated low toxicity to HeLa cells at therapeutic concentrations of loaded PS. Compared to free PS solution, the synthesized BSA-PS NPs generated the singlet oxygen more effectively under laser irradiation at 660 nm. In addition, due to presence of various chemical groups on the surface of BSA-PS NPs, they are capable to adsorb on cell surface and accumulate in cells due to cellular uptake mechanisms. Owing to combination of PD and cell uptake advantages, BSA-PS NPs demonstrated higher efficacy of photodynamic damage to cancer cells as compared to free PS at equivalent concentrations. These results suggest that non-targeted BSA-PS NPs with high PD activity and low-fabrication costs of are promising candidates for transfer to PD clinic treatments.

  11. Monte Carlo simulations for optimal light delivery in photodynamic therapy of non-melanoma skin cancer

    International Nuclear Information System (INIS)

    Valentine, R M; Ibbotson, S H; Moseley, H; Wood, K; Brown, C T A

    2012-01-01

    The choice of light source is important for the efficacy of photodynamic therapy (PDT) of non-melanoma skin cancer. We simulated the photodynamic dose (PDD) delivered to a tumour during PDT using theoretical radiation transfer simulations performed via our 3D Monte Carlo radiation transfer (MCRT) model for a range of light sources with light doses up to 75 J cm −2 . The PDD delivered following superficial irradiation from (A) non-laser light sources, (B) monochromatic light, (C) alternate beam diameters and (D) re-positioning of the tumour within the tissue was computed. (A) The final PDD deposited to the tumour at a depth of 2 mm by the Paterson light source was 2.75, 2.50 and 1.04 times greater than the Waldmann 1200, Photocure and Aktilite, respectively. (B) Tumour necrosis occurred at a depth of 2.23 mm and increased to 3.81 mm for wavelengths 405 and 630 nm, respectively. (C) Increasing the beam diameter from 10 to 50 mm had very little effect on depth of necrosis. (D) As expected, necrosis depths were reduced when the tumour was re-positioned deeper into the tissue. These MCRT simulations show clearly the importance of choosing the correct light source to ensure optimal light delivery to achieve tumour necrosis. (paper)

  12. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

    Science.gov (United States)

    Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

    2015-01-01

    Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

  13. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

    Directory of Open Access Journals (Sweden)

    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  14. Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Juan Zhang

    2018-06-01

    Full Text Available The use of photodynamic therapy (PDT and development of novel photosensitizers (PSs for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.

  15. Squaraine dyes for photodynamic therapy: study of their cytotoxicity and genotoxicity in bacteria and mammalian cells.

    Science.gov (United States)

    Ramaiah, Danaboyina; Eckert, Inge; Arun, Kalliat T; Weidenfeller, Lydia; Epe, Bernd

    2002-12-01

    Halogenated squaraine dyes are characterized by long wavelength absorption (>600 nm) and high triplet yields and therefore represent new types of photosensitizers that could be useful for photodynamic therapy. We have analyzed the cytotoxicity and genotoxicity of the bromo derivative 1, the iodo derivative 2 and the corresponding nonhalogenated dye 3 in the absence and presence of visible light. At concentrations of 1-2 microM, 1 and 2 reduced the cloning efficiency of AS52 Chinese hamster ovary cells to less than 1% under conditions that were well tolerated in the dark. Similarly, the proliferation of L5178Y mouse lymphoma cells was inhibited by photoexcited 1 and 2 with high selectivity. The squaraine 3 was much less efficient. Both 1 and 2 induced only few mutations in the gpt locus of the AS52 cells in the presence of light and were not mutagenic in the dark. No mutagenicity with and without irradiation was observed in Salmonella typhimurium TA100 and TA2638. However, both 1 and 2 plus light increased the frequency of micronuclei in AS52 cells. The results indicate that halogenated squaraines exhibit photobiological properties in vitro that are favorable for photodynamic therapeutical applications.

  16. Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

    Science.gov (United States)

    Rangel, Carlos M; Villota, Eva; Fernández-Vega González, Álvaro; Sanchez-Avila, Ronald M

    2017-12-01

    Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. Polypoidal choroidal vasculopathy and choroidal nevus. The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  17. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Unterweger H

    2015-11-01

    Full Text Available Harald Unterweger,1 Daniel Subatzus,1 Rainer Tietze,1 Christina Janko,1 Marina Poettler,1 Alfons Stiegelschmitt,2 Matthias Schuster,3 Caroline Maake,4 Aldo R Boccaccini,5 Christoph Alexiou11ENT Department, Section of Experimental Oncology and Nanomedicine (SEON, Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen; 2Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, 3Materials for Electronics and Energy Technology, Department of Materials Science and Engineering, University Erlangen-Nürnberg, Erlangen, Germany; 4Institute of Anatomy, University of Zurich, Winterthurerstr, Zurich, Switzerland; 5Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany Abstract: Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55–85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5–5.0 nm. Surface chemistry of those

  18. Quantitative approach to skin field cancerization using a nanoencapsulated photodynamic therapy agent: a pilot study

    Directory of Open Access Journals (Sweden)

    Passos SK

    2013-02-01

    Full Text Available Simone K Passos,1,2 Paulo EN de Souza,3 Priscila KP Soares,1,3 Danglades RM Eid,1,2 Fernando L Primo,4 Antonio Cláudio Tedesco,4 Zulmira GM Lacava,1 Paulo C Morais3,51University of Brasília, Institute of Biological Sciences, DF, Brazil; 2Foundation for Teaching and Research on Health Sciences, Brasília, DF, Brazil; 3University of Brasília, Institute of Physics, Brasília, DF, Brazil; 4Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, Laboratory of Photobiology and Photomedicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; 5Department of Control Science and Engineering, Hua-Zhong University of Science and Technology, Wuham, People's Republic of ChinaBackground: This paper introduces a new nanoformulation of 5-aminolevulinic acid (nano-ALA as well as a novel quantitative approach towards evaluating field cancerization for actinic keratosis and/or skin photodamage. In this pilot study, we evaluated field cancerization using nano-ALA and methyl aminolevulinate (MAL, the latter being commercialized as Metvix®.Methods and results: Photodynamic therapy was used for the treatment of patients with selected skin lesions, whereas the fluorescence of the corresponding photosensitizer was used to evaluate the time evolution of field cancerization in a quantitative way. Field cancerization was quantified using newly developed color image segmentation software. Using photodynamic therapy as the precancer skin treatment and the approach introduced herein for evaluation of fluorescent area, we found that the half-life of field cancerization reduction was 43.3 days and 34.3 days for nano-ALA and MAL, respectively. We also found that nano-ALA targeted about 45% more skin lesion areas than MAL. Further, we found the mean reduction in area of skin field cancerization was about 10% greater for nano-ALA than for MAL.Conclusion: Although preliminary, our findings indicate that the efficacy of nano-ALA in

  19. Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

    Science.gov (United States)

    Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

    2018-06-09

    Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

  20. Empirical antimicrobial therapy of acute dentoalveolar abscess

    Directory of Open Access Journals (Sweden)

    Matijević Stevo

    2009-01-01

    Full Text Available Background/Aim. The most common cause of acute dental infections are oral streptococci and anaerobe bacteria. Acute dentoalveolar infections are usually treated surgically in combination with antibiotics. Empirical therapy in such infections usually requires the use of penicillin-based antibiotics. The aim of this study was to investigate the clinical efficiency of amoxicillin and cefalexin in the empirical treatment of acute odontogenic abscess and to assess the antimicrobial susceptibility of the isolated bacteria in early phases of its development. Methods. This study included 90 patients with acute odontogenic abscess who received surgical treatment (extraction of a teeth and/or abscess incision and were divided into three groups: two surgicalantibiotic groups (amoxicillin, cefalexin and the surgical group. In order to evaluate the effects of the applied therapy following clinical symptoms were monitored: inflammatory swelling, trismus, regional lymphadentytis and febrility. In all the patients before the beginning of antibiotic treatment suppuration was suched out of the abscess and antibiotic susceptibility of isolated bacteria was tested by using the disk diffusion method. Results. The infection signs and symptoms lasted on the average 4.47 days, 4.67 days, and 6.17 days in the amoxicillin, cefalexin, and surgically only treated group, respectively. A total of 111 bacterial strains were isolated from 90 patients. Mostly, the bacteria were Gram-positive facultative anaerobs (81.1%. The most common bacteria isolated were Viridans streptococci (68/111. Antibiotic susceptibility of isolated bacteria to amoxicillin was 76.6% and cefalexin 89.2%. Conclusion. Empirical, peroral use of amoxicillin or cefalexin after surgical treatment in early phase of development of dentoalveolar abscess significantly reduced the time of clinical symptoms duration in the acute odontogenic infections in comparison to surgical treatment only. Bacterial strains

  1. Ultrasonic activation and chemical modification of photosensitizers enhances the effects of photodynamic therapy against Enterococcus faecalis root-canal isolates.

    Science.gov (United States)

    Tennert, C; Drews, A M; Walther, V; Altenburger, M J; Karygianni, L; Wrbas, K T; Hellwig, E; Al-Ahmad, A

    2015-06-01

    The aim of this study was to evaluate the effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilms in artificially infected root canals using modified photosensitizers and passive ultrasonic activation. Two hundred and seventy extracted human teeth with one root canal were instrumented utilizing ProTaper files, autoclaved, infected with E. faecalis T9 for 72 h and divided into different groups: irrigation with 3% sodium hypochlorite (NaOCl), 20% ethylenediaminetetraacetic acid (EDTA), or 20% citric acid, PDT without irrigation, PDT accompanied by irrigation with NaOCl, EDTA, or citric acid, PDT using an EDTA-based photosensitizer or a citric-acid-based photosensitizer and PDT with ultrasonic activation of the photosensitizer. A 15 mg/ml toluidine blue served as the photosensitizer, activated by a 100 mW LED light source. Sterile paper points were used for sampling the root canals and dentin chips were collected to assess the remaining contamination after treatment. Samples were cultured on blood agar plates and colony forming units were quantified. PDT alone achieved a reduction in E. faecalis counts by 92.7%, NaOCl irrigation alone and combined with PDT by 99.9%. The antibacterial effects increased by the combination of irrigation using EDTA or citric acid and PDT compared to irrigation alone. More than 99% of E. faecalis were killed using PDT with the modified photosensitizers and ultrasonic activation. NaOCl based disinfection achieved the highest antimicrobial effect. Using PDT with an EDTA-based or citric-acid-based phozosensitizer or activating the photosensitizer with ultrasound resulted in a significantly higher reduction in E. faecalis counts compared to conventional PDT. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2017-11-01

    Full Text Available Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT and antivascular endothelial growth factor (VEGF therapy is effective in the management of chronic central serous chorioretinopathy (CSC recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT, fluorescein angiography (FA, and most with indocyanine green angiography (ICGA followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept. Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010 by 4 months after treatment (1.63±1.18 months. Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019. Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in

  3. Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis.

    Science.gov (United States)

    Tang, Kai; Si, Jun-Kang; Guo, Da-Dong; Cui, Yan; Du, Yu-Xiang; Pan, Xue-Mei; Bi, Hong-Sheng

    2015-01-01

    To compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV). A systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis. Three RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P≤0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All Pcompare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.

  4. Review of dermatology use of 5-aminolevulinic acid photodynamic therapy in China from 1997 to 2013

    Science.gov (United States)

    Wang, Peiru; Zhang, Guolong; Wang, Xiuli

    2015-07-01

    The prodrug 5-aminolevulinic acid (ALA) and its ester derivatives have been used in photodynamic therapy (PDT) in dermatology worldwide. In China, ALA-PDT was first used to treat urethral condylomata acuminata and non-melanoma skin cancers in 1997. A powder formulation of ALA hydrochloride was approved by the Chinese Food and Drug Administration for the treatment of condylomata acuminata in 2007. Large successful experience of treating condylomatas was accumulated compared with Western countries. Meanwhile, numerous clinical studies as well as off-label use of ALAPDT have been carried out in China. To reflect the progress of ALA-PDT in China, several major Chinese and English databases were searched and published data were reviewed in this article.

  5. Development of Flexible Luminous Fabrics for Photodynamic Therapy in Biomedical Applications

    Institute of Scientific and Technical Information of China (English)

    KONG Lingbao; BAI Ziqian

    2017-01-01

    Fabrics integrating with side-emitting polymer optical fiber (SE-POF) have great potentials for photodynamic therapy (PDT),which is a form of phototherapy recognized as a treatment strategy that is both minimally invasive and minimally toxic.Preliminary research has been undertaken to develop flexible luminous fabrics (FLF) device for PDT used in biomedical applications.The FLF device consists of SE-POFs,textile substrates,light source (LEDs or laser) with proper wavelength,and optical fiber coupling,etc.Different patterns of the fabrics were designed and fabricated purposely,and the light illumination effect was tested including the light power emitting from the patterned optical fiber fabrics,the stability of the illumination,and the light with different wavelengths.The work contributes to the successful development of an efficient and pain-alleviated illumination device for PDT in biomedical application.

  6. Effect of axial length on laser spot size during photodynamic therapy: an experimental study in monkeys.

    Science.gov (United States)

    Kondo, Mineo; Ito, Yasuki; Miyata, Kentaro; Kondo, Nagako; Ishikawa, Kohei; Terasaki, Hiroko

    2006-01-01

    To investigate the effect of shorter axial length on the laser spot size and laser energy during photodynamic therapy (PDT) in monkeys. Experimental study with four rhesus monkeys. PDT was performed on the normal retina of monkeys whose ocular axial lengths are shorter (19.55 to 20.25 mm) than that of humans. After the PDT, the eyes were enucleated, and the diameter of the irradiated laser spot was measured with a microcaliper. The area of actual laser spot was only 0.56 to 0.61 times of the planned area, which indicated that the laser energy/area was 1.64 to 1.78 times more intense than planned initially. These results are the in vivo demonstration that the diameter of PDT laser spot is smaller for eyes with shorter axial lengths.

  7. Relevance of PDT-induced inflammatory response for the outcome of photodynamic therapy

    Science.gov (United States)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai

    2001-07-01

    The treatment of solid cancerous lesions by photodynamic therapy (PDT) elicits an acute host reaction primarily manifested as a strong, rapidly developing inflammatory response. It is becoming increasingly clear that the destructive impact of the inflammatory process is directly responsible for the so-called indirect damage in PDT-treated tumors. The loss of vascular homeostasis followed by massive damage to vascular and perivascular regions in PDT- treated tumors and the ensuing tumor antigen-specific immunity, are direct consequences of critical initiating events including the action of complement, activation of poly(ADP-ribose)polymerase (PARP) and ischemia/reperfusion insult, and the associated cascades of tissue-destructive responses. Hence, the effectiveness of PDT as an anti- cancer modality is largely owed to the fact that it instigates a comprehensive engagement of powerful innate host defense mechanisms.

  8. Indwelling Stent Embedded with Light-Emitting Diodes for Photodynamic Therapy of Malignant Biliary Obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Baran, Timothy M., E-mail: timothy.baran@rochester.edu [University of Rochester Medical Center, Department of Imaging Sciences (United States); Mironov, Oleg, E-mail: oleg.mironov@uhn.ca [University Health Network, The Joint Department of Medical Imaging (Canada); Sharma, Ashwani K., E-mail: Ashwani-Sharma@URMC.Rochester.edu; Foster, Thomas H., E-mail: thomas.foster@rochester.edu [University of Rochester Medical Center, Department of Imaging Sciences (United States)

    2016-06-15

    PurposeWe describe the design and preliminary characterization of a stent incorporating light-emitting diodes (LEDs) for photodynamic therapy (PDT) of malignant biliary obstruction.MethodsA prototype was constructed with red (640 nm) LEDs embedded in a 14.5 French polyurethane tube. The device was evaluated for optical power and subjected to physical and electrical tests. PDT-induced reactive oxygen species were imaged in a gel phantom.ResultsThe stent functioned at a 2.5-cm bend radius and illuminated for 6 months in saline. No stray currents were detected, and it was cool after 30 minutes of operation. Optical power of 5–15 mW is applicable to PDT. Imaging of a reactive oxygen indicator showed LED-stent activation of photosensitizer.ConclusionsThe results motivate biological testing and design optimization.

  9. Indwelling Stent Embedded with Light-Emitting Diodes for Photodynamic Therapy of Malignant Biliary Obstruction

    International Nuclear Information System (INIS)

    Baran, Timothy M.; Mironov, Oleg; Sharma, Ashwani K.; Foster, Thomas H.

    2016-01-01

    PurposeWe describe the design and preliminary characterization of a stent incorporating light-emitting diodes (LEDs) for photodynamic therapy (PDT) of malignant biliary obstruction.MethodsA prototype was constructed with red (640 nm) LEDs embedded in a 14.5 French polyurethane tube. The device was evaluated for optical power and subjected to physical and electrical tests. PDT-induced reactive oxygen species were imaged in a gel phantom.ResultsThe stent functioned at a 2.5-cm bend radius and illuminated for 6 months in saline. No stray currents were detected, and it was cool after 30 minutes of operation. Optical power of 5–15 mW is applicable to PDT. Imaging of a reactive oxygen indicator showed LED-stent activation of photosensitizer.ConclusionsThe results motivate biological testing and design optimization.

  10. Idiopathic elastosis perforans serpiginosa with satisfactory response after 5-ALA photodynamic therapy.

    Science.gov (United States)

    Alique-García, S; Company-Quiroga, J; Horcajada-Reales, C; Echeverría-García, B; Tardío-Dovao, J C; Borbujo, J

    2018-03-01

    Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases. Topical photosensitizers employed in dermatology are 5-aminolevulinic acid (5 ALA) and methyl aminolevulinate, classically used for the treatment of superficial non-melanoma skin cancer and their precursors. Recently the efficacy of PDT has been introduced in other benign diseases. Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibers. Management of this condition is complicated, various methods have been used but with limited success. We report a case of EPS in a 30-yeard-old woman treated with 5 ALA-PDT. After 4 sessions the lesions have almost completely disappeared with no residual side effects. Therefore we present an effective and safe alternative for the treatment of EPS. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Photodynamic therapy on spontaneous tumors of dogs and cats: a ten-year study

    Science.gov (United States)

    Fonda, Diego

    1992-06-01

    Since 1981, more than fifty spontaneous tumors of dogs and cats were treated by photodynamic therapy with hematoporphyrins in the surgery department of the University of Milan. Therapeutic results proved to be successful and promising in certain forms of cancer and will be compared in the future with the effectiveness of other photosensitizer drugs like phatolocyanines derivatives. Applied hematoporphyrins phototherapy methods included: (1) injection of hematoporphyrins derivative (HpD) and irradiation with laser light at 631 nanometers, using a Rhodamine B dye laser; (2) injection of the active component of hematoporphyrin derivative (DHE) and irradiation with a Rhodamine B dye laser; and (3) injection of DHE and irradiation with laser light at 628 nanometers using a gold vapor laser. More frequently treated tumor sites were oral and nasal cavities. Other localizations were mucous membranes of the glans and stomach. Nineteen histological types were diagnosed in treated tumors.

  12. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    Science.gov (United States)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  13. Daylight-mediated photodynamic therapy of basal cell carcinomas - an explorative study

    DEFF Research Database (Denmark)

    Wiegell, S R; Skødt, V; Wulf, H C

    2014-01-01

    BACKGROUND: Studies have shown that daylight-photodynamic therapy (PDT) is an effective treatment of actinic keratoses, nearly pain free and more convenient for both the clinics and patients. Treatment of basal cell carcinomas (BCCs) is another main indication for PDT. OBJECTIVES: The aim...... of this open, uncontrolled, prospective explorative study was to evaluate the efficacy of daylight-PDT for BCCs. METHODS: Twenty-one patients with a total of 32 BCCs located in the face, scalp, chest, back and lower leg received one cycle of daylight-methyl aminolevulinate (MAL)-PDT, consisting of two...... treatments 1 week apart. After sunscreen application and lesion preparation, MAL was applied and patients exposed themselves to daylight for 2½ h. Daylight exposure was monitored with a wrist-borne dosimeter. RESULTS: At 3-month follow-up, complete response was seen in 30 lesions (94%) and in 19 patients (90...

  14. Successful treatment of a large oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy

    Directory of Open Access Journals (Sweden)

    Yu-Chao Chang

    2013-03-01

    Full Text Available Studies have shown that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT can be used successfully for the treatment of oral verrucous hyperplasia (OVH. Studies have also demonstrated that cryotherapy could be used as a treatment modality for OVH lesions. In this case report, we tested the efficacy of topical ALA-PDT, combined with cryogun cryotherapy, for an extensive OVH lesion on the right buccal mucosa of a 65-year-old male areca quid chewer. The tumor was cleared after six treatments of combined topical ALA-PDT and cryogun cryotherapy. No recurrence of the lesion was found after a follow-up period of 18 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. The treatment course may be slightly shortened with this combined protocol and was well tolerated by the patient.

  15. Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

    Science.gov (United States)

    Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

    2017-05-30

    The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

  16. Chorioretinal anastomosis after photodynamic therapy for polypoidal choroidal vasculopathy: CRA after PDT for PCV.

    Science.gov (United States)

    Yodoi, Yuko; Tsujikawa, Akitaka; Otani, Atsushi; Aikawa, Hiroko; Yoshimura, Nagahisa

    2008-08-01

    An 80-year-old woman was treated with photodynamic therapy (PDT) to the left eye for polypoidal choroidal vasculopathy (PCV). About 3 months after PDT, her left eye developed a chorioretinal anastomosis with severe atrophy of the retinal pigment epithelium in the macula; visual acuity in this eye was 20/1000. She received a second session of PDT, plus an intravitreal injection of triamcinolone acetonide. About 3 months after the second treatment, the chorioretinal anastomosis was enlarged and the retinal vessels involved in the anastomosis were more dilated. About 1 year after the first PDT, visual acuity in the left eye had stabilized at 20/400. Development of a chorioretinal anastomosis is a distinct possibility following PDT in eyes with PCV, and can lead to poor visual recovery.

  17. Photodynamic therapy in surgical treatment of patients by a skin melanom

    Directory of Open Access Journals (Sweden)

    G. I. Gafton

    2013-01-01

    Full Text Available In experimental and clinical research carried out studying of influence of neoadjyuvant photodynamic therapy on T- and B-cellular immune answer in surgical treatment of patients of a melanoma of skin of the I–III stage. PDT was executed to 25 patients two days prior to surgical removal of primary tumor from July, 2012 to January, 2013. As a result of the conducted research it was revealed that: the increase in concentration fotoditaziny doesn‘t lead to increase in quantity of tumoral cages at stages early apoptosis; lengthening of time of an exposition leads to increase in a share of late forms apoptosis, and FDT use with fotoditaziny in a dose of 50,0 mg with the subsequent radiation (662 nanometers, 400 J in 2 days prior to surgical intervention promotes T- and B-cellular link of immune system.

  18. Photodynamic Therapy Activated by Intense Pulsed Light in the Treatment of Nonmelanoma Skin Cancer

    Directory of Open Access Journals (Sweden)

    Domenico Piccolo

    2018-02-01

    Full Text Available Photodynamic therapy (PDT with topical 5-aminolevulinic acid (ALA or methyl aminolevulinate (MAL has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK, Bowen’s disease (BD, and superficial basal cell carcinoma (sBCC. PDT is traditionally performed in association with broad-spectrum continuous-wave light sources, such as red or blue light. Recently, intense pulsed light (IPL devices have been investigated as an alternative light source for PDT in the treatment of nonmelanoma skin cancers (NMSC. We herein report our observational findings in a cohort of patients with a diagnosis of AK, sBCC, and BD that is treated with MAL-PDT using IPL, as well as we review published data on the use of IPL-PDT in NMSC.

  19. Systematic immunosuppression induced by photodynamic therapy (PDT) is adoptively transferred by macrophages

    International Nuclear Information System (INIS)

    Lynch, D.H.; Haddad, S; King, V.J.; Ott, M.J.; Jolles, C.J.; Straight, R. C.

    1989-01-01

    The purpose of this study was to determine whether photodynamic therapy induced suppression of contact hypersensitivity (CHS) responses was an active phenomenon that could be adoptively transferred by viable splenocytes from PDT-treated mice. Although induction of adoptively transferable suppressor cells in PDT-treated mice required exposure to antigen, the suppressor cells were found to be antigen nonspecific in their function. Furthermore, splenocytes from PDT-treated mice were capable of generating levels of allospecific cytotoxic T lymphocyte (CTL) activity which were comparable to those generated by normal control mice, but the ability of irradiated spleen cells from PDT-treated mice to stimulate a mixed lymphocyte response (MLR) was dramatically impaired. Finally, chromatographic separation of T cells, B cells and macrophages showed that the cell type which mediates adoptively transferable suppression of CHS responsiveness is in the macrophage lineage. (author)

  20. Minimally invasive neuronavigator-guided microsurgery and photodynamic therapy for gliomas.

    Science.gov (United States)

    Wang, Yezhong; Lei, Ting; Wang, Zhi

    2009-06-01

    In order to evaluate the effectiveness of neuronavigator-guided microsurgery and keyhole technique for the resection of gliomas, a total of 60 patients with gliomas were exactly located by using neuronavigator during microsurgery. Forty deep-seated gliomas were resected through a keyhole operative approach. Thirty out of the 60 cases were subjected to photodynamic therapy (PDT) after tumor resection. The therapeutic effectiveness of all the cases was recorded and analyzed. The results showed that glioma was totally resected in 52 cases (86.7%), subtotally in 5 (8.3%), and most partially in 3 (5%). Neurological deficits occurred postoperatively in 4 cases. One patient died of multiple system organ failure 4 days after operation. It was concluded that the application of minimally invasive technique could dramatically decrease surgical complications following resection of glioma, and its combination with PDT could obviously improve the quality of life of patients and prolong the survival time.

  1. Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations

    Directory of Open Access Journals (Sweden)

    Gloria Mazzone

    2016-02-01

    Full Text Available The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600–800 nm. The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenylchlorin (Foscan© already used in the photodynamic therapy (PDT protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents.

  2. Primary photochemical processes for Pt(iv) diazido complexes prospective in photodynamic therapy of tumors.

    Science.gov (United States)

    Shushakov, Anton A; Pozdnyakov, Ivan P; Grivin, Vjacheslav P; Plyusnin, Victor F; Vasilchenko, Danila B; Zadesenets, Andrei V; Melnikov, Alexei A; Chekalin, Sergey V; Glebov, Evgeni M

    2017-07-25

    Diazide diamino complexes of Pt(iv) are considered as prospective prodrugs in oxygen-free photodynamic therapy (PDT). Primary photophysical and photochemical processes for cis,trans,cis-[Pt(N 3 ) 2 (OH) 2 (NH 3 ) 2 ] and trans,trans,trans-[Pt(N 3 ) 2 (OH) 2 (NH 3 ) 2 ] complexes were studied by means of stationary photolysis, nanosecond laser flash photolysis and ultrafast kinetic spectroscopy. The process of photolysis is multistage. The first stage is the photosubstitution of an azide ligand to a water molecule. This process was shown to be a chain reaction involving redox stages. Pt(iv) and Pt(iii) intermediates responsible for the chain propagation were recorded using ultrafast kinetic spectroscopy and nanosecond laser flash photolysis. The mechanism of photosubstitution is proposed.

  3. Light-Emitting Diode-Based Illumination System for In Vitro Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Defu Chen

    2012-01-01

    Full Text Available The aim of this study is to develop a light-emitting diode- (LED- based illumination system that can be used as an alternative light source for in vitro photodynamic therapy (PDT. This illumination system includes a red LED array composed of 70 LEDs centered at 643 nm, an air-cooling unit, and a specific-designed case. The irradiance as a function of the irradiation distance between the LED array and the sample, the homogeneity and stability of irradiation, and the effect of long-time irradiation on culture medium temperature were characterized. Furthermore, the survival rate of the CNE1 cells that sensitized with 5-aminolevulinic acid after PDT treatment was evaluated to demonstrate the efficiency of the new LED-based illumination system. The obtained results show that the LED-based illumination system is a promising light source for in vitro PDT that performed in standard multiwell plate.

  4. Serum levels of hematoporphyrin derivatives in the photodynamic therapy of malignant tumors

    Science.gov (United States)

    Chan, H. K.; Low, K. S.; Haji Baba, A. S.; Arimbalam, S.; Yip, C. H.; Chang, K. W.; Baskaran, G.; Lo, Y. L.; Jayalakshmi, P.; Looi, L. M.; Tan, N. H.

    1995-03-01

    In photodynamic therapy (PDT), red light is administered 24 - 72 hours post intravenous (i.v.) injection of hematoporphyrin derivatives (HpD). In an earlier animal model study, more effective therapeutic response was obtained when red light irradiation was carried out 15 mins after the injection of HpD. The effectiveness of this immediate PDT protocol has been correlated to the high serum level of HpD immediately after administration and the destruction of the microcirculation system as the dominant tumor destruction mechanism. This study examines the pharmacokinetics and the serum levels of HpD in rats and also in human patients. Such data can assist in defining the optimum time delay for light irradiation in the PDT of cancer.

  5. Micro-Encapsulated Porphyrins and Phthalocyanines - New Formulations in Photodynamic Therapy

    Science.gov (United States)

    Ion, R. M.

    2017-06-01

    Photodynamic therapy (PDT), as an innovative method for cancer tretament is based on a concerted action of some drugs, called sensitizers, which generate reactive oxygen species via a photochemical mechanism, leading to cellular necrosis or apoptosis. The present work aims at loading some sensitizers, as porphyrins (P) and phthalocyanines (Pc) into alginate particles. Particles were prepared by dropping alginate into an aqueous solution containing P or Pc and CaCl2, which allows the formation of particles through ionic crosslinking. It was obtained P or Pc loaded alginate beads with an average diameter of about 100 μm. For these systems, this paper analyses the spectroscopic properties, encapsulation into microcapsules, controlled releasing action and their photosensitizer capacity (singlet oxygen generation).

  6. In vitro toxicity testing of zinc tetrasulfophthalocyanines in fibroblast and keratinocyte cells for the treatment of melanoma cancer by photodynamic therapy

    CSIR Research Space (South Africa)

    Maduray, K

    2011-05-01

    Full Text Available and United States [3]. The standard oncology treatment for melanoma cancer is surgi- Available online xxxx Keywords: Photodynamic therapy Zinc tetrasulfophthalocyanines Melanoma cancer Phthalocyanines 1011-1344/$ - see front matter � 2011 Elsevier B... of cancer, 567 The Lancet Oncology 1 (2000) 4212?4219. 568 [15] K. Plaetzer, B. Krammer, J. Berlanda, F. Berr, T. Kiesslich, Photophysics and 569 photochemistry of photodynamic therapy: fundamental aspects, Laser Medical 570 Science 24 (2009) 259...

  7. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy.

    Science.gov (United States)

    Unterweger, Harald; Subatzus, Daniel; Tietze, Rainer; Janko, Christina; Poettler, Marina; Stiegelschmitt, Alfons; Schuster, Matthias; Maake, Caroline; Boccaccini, Aldo R; Alexiou, Christoph

    2015-01-01

    Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55-85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5-5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs' targeting abilities with hypericin's phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer.

  8. Photodynamic therapy in the management of actinic keratosis: Retrospective evaluation of outcome.

    Science.gov (United States)

    Jerjes, Waseem; Hamdoon, Zaid; Abdulkareem, Ali A; Hopper, Colin

    2017-03-01

    Photodynamic therapy (PDT) is a minimally invasive intervention used in the management of tissue disorders. In this retrospective study, a total of 62 patients with actinic keratosis (AKs) were treated with surface illumination PDT. Comparisons with the clinical features, rate of recurrence as well as malignant transformation and overall outcome were made. The medical records of 62 consecutive patients who presented with suspicious skin lesions and diagnosed with AKs were examined. These patients with 178 AKs lesions were treated with surface illumination methyl aminolevulinate-photodynamic therapy (MAL-PDT). The 16% strength cream (MAL) was applied topically 3h prior to tissue illumination. A single-channel 628nm diode laser was used for illumination and light was delivered at 100J/cm 2 per site. These patients were followed-up for a mean of 7.4 years. Eight recurrences were reported after the first round of MAL-PDT, and two recurrences after the second round. Malignant transformation to squamous cell carcinoma (SCC) was noted in 2 patients only. The 3-year outcome resulted in 60 patients with complete response (CR), and this was maintained at the final outcome (last clinic review). Assessment of lesional outcome vs. response showed that 175/178 treated lesions had complete response (CR) at 3-year follow-up, which increased to 176/178 lesions at the last clinic follow-up. MAL-PDT offers an effective treatment for AKs lesions with excellent cosmetic outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, Sean R H; Gertner, Mark R; Bogaards, Arjen; Sherar, Michael D; Wilson, Brian C [Division of Biophysics and Bioimaging, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Weersink, Robert A; Giewercer, David [Laboratory for Applied Biophysics, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Haider, Masoom A [Joint Department of Medical Imaging, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Scherz, Avigdor [Department of Plant Science, Weizmann Institute of Science, PO Box 26, Rehovot 76100 (Israel); Elhilali, Mostafa [Department of Surgery, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6 (Canada); Chin, Joseph L [Department of Oncology, University of Western Ontario, 800 Commissioners Road East, PO Box 5010, London, Ontario N6A 5W9 (Canada); Trachtenberg, John [Department of Urology, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)], E-mail: wilson@uhnres.utoronto.ca

    2009-04-21

    With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately {+-}2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D{sub 90}, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D{sub 90} less than 23 J cm{sup -2} had complete biopsy response, while 8/13 (62%) of patients with a D{sub 90} greater than 23 J cm{sup -2} had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

  10. A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy

    International Nuclear Information System (INIS)

    Kang-Hsin Wang, Ken; Mitra, Soumya; Foster, Thomas H.

    2007-01-01

    We have developed a comprehensive theoretical model for rigorously describing the spatial and temporal dynamics of oxygen ( 3 O 2 ) consumption and transport and microscopic photodynamic dose deposition during photodynamic therapy (PDT) in vivo. Previously published models have been improved by considering perfused vessels as a time-dependent 3 O 2 source and linking the 3 O 2 concentration in the vessel to that within the tissue through the Hill equation. The time-dependent photochemical 3 O 2 consumption rate incorporates sensitizer photobleaching effects and an experimentally determined initially nonuniform photosensitizer distribution. The axial transport of 3 O 2 is provided for in the capillaries and in the surrounding tissue. A self-sensitized singlet oxygen ( 1 O 2 )-mediated bleaching mechanism and the measured, initially nonuniform distribution of meso-tetrahydroxyphenyl chlorin at 3 h after intravascular administration were used to demonstrate the capabilities of the model. Time-evolved distributions of 3 O 2 concentration were obtained by numerically solving two-dimensional diffusion-with-reaction equations both in the capillary and the adjacent tissue. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin- 3 O 2 saturation (SO 2 ) within the vessels, irreversible sensitizer degradation due to photobleaching, and the microscopic distributions of 3 O 2 , sensitizer concentration, and 1 O 2 dose deposition under various irradiation conditions. The simulations reveal severe axial gradients in 3 O 2 and in photodynamic dose deposition in response to a wide range of clinically relevant treatment parameters. Thus, unlike former Krogh cylinder-based models, which assume a constant 3 O 2 concentration at the vessel, this new model identifies conditions in which 3 O 2 depletion and minimal deposition of reacting 1 O 2 exist near the end of axial segments of

  11. Prospects in the Application of Photodynamic Therapy in Oral Cancer and Premalignant Lesions

    Science.gov (United States)

    Saini, Rajan; Lee, Nathan V.; Liu, Kelly Y. P.; Poh, Catherine F.

    2016-01-01

    Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment. PMID:27598202

  12. Prevalence and treatment patterns of ranibizumab and photodynamic therapy in a tertiary care setting in Malaysia.

    Science.gov (United States)

    Mohamad, Nur Afiqah; Ramachandran, Vasudevan; Ismail, Patimah; Mohd Isa, Hazlita; Chan, Yoke Mun; Ngah, Nor Fariza; Md Bakri, Norshakimah; Ching, Siew Mooi; Hoo, Fan Kee; Wan Sulaiman, Wan Aliaa

    2017-01-01

    To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy (PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014. Study subjects were recruited retrospectively using the Electronic Medical Record (EMR) database software in Hospital Selayang. Demographic data, medical history, diagnostic procedure, treatments and diagnosis of patients were recorded. The five-year analysis included 821 patients with a mean age of 65.9±11.73y. Overall, there were a higher number of males (63.1%) and a higher number of Chinese (47.4%) patients. Among the 821 patients, 62.9% received ranibizumab injection followed by 19.2% PDT therapy and 17.9% had ranibizumab combined with PDT therapy. Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) were the most common retinal eye diseases reported, recording prevalence of 25.0% and 45.6%, respectively. The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014. In terms of treatment, following multiple logistic regression, AMD was associated with the subjects being more likely to have received ranibizumab monotherapy ( P Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD, while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.

  13. Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma.

    Science.gov (United States)

    Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; de Azevedo, Ricardo Bentes

    2014-01-01

    Malignant melanoma is the most aggressive form of skin cancer and has been traditionally considered difficult to treat. The worldwide incidence of melanoma has been increasing faster than any other type of cancer. Early detection, surgery, and adjuvant therapy enable improved outcomes; nonetheless, the prognosis of metastatic melanoma remains poor. Several therapies have been investigated for the treatment of melanoma; however, current treatment options for patients with metastatic disease are limited and non-curative in the majority of cases. Photodynamic therapy (PDT) has been proposed as a promising minimally invasive therapeutic procedure that employs three essential elements to induce cell death: a photosensitizer, light of a specific wavelength, and molecular oxygen. However, classical PDT has shown some drawbacks that limit its clinical application. In view of this, the use of nanotechnology has been considered since it provides many tools that can be applied to PDT to circumvent these limitations and bring new perspectives for the application of this therapy for different types of diseases. On that ground, this review focuses on the potential use of developing nanotechnologies able to bring significant benefits for anticancer PDT, aiming to reach higher efficacy and safety for patients with malignant melanoma.

  14. Using Fourier transform infrared spectroscopy to evaluate biological effects induced by photodynamic therapy.

    Science.gov (United States)

    Lima, Cassio A; Goulart, Viviane P; Correa, Luciana; Zezell, Denise M

    2016-07-01

    Vibrational spectroscopic methods associated with multivariate statistical techniques have been succeeded in discriminating skin lesions from normal tissues. However, there is no study exploring the potential of these techniques to assess the alterations promoted by photodynamic effect in tissue. The present study aims to demonstrate the ability of Fourier Transform Infrared (FTIR) spectroscopy on Attenuated total reflection (ATR) sampling mode associated with principal component-linear discriminant analysis (PC-LDA) to evaluate the biochemical changes caused by photodynamic therapy (PDT) in skin neoplastic tissue. Cutaneous neoplastic lesions, precursors of squamous cell carcinoma (SCC), were chemically induced in Swiss mice and submitted to a single session of 5-aminolevulinic acid (ALA)-mediated PDT. Tissue sections with 5 μm thickness were obtained from formalin-fixed paraffin-embedded (FFPE) and processed prior to the histopathological analysis and spectroscopic measurements. Spectra were collected in mid-infrared region using a FTIR spectrometer on ATR sampling mode. Principal Component-Linear Discriminant Analysis (PC-LDA) was applied on preprocessed second derivatives spectra. Biochemical changes were assessed using PCA-loadings and accuracy of classification was obtained from PC-LDA . Sub-bands of Amide I (1,624 and 1,650 cm(-1) ) and Amide II (1,517 cm(-1) ) indicated a protein overexpression in non-treated and post-PDT neoplastic tissue compared with healthy skin, as well as a decrease in collagen fibers (1,204, 1,236, 1,282, and 1,338 cm(-1) ) and glycogen (1,028, 1,082, and 1,151 cm(-1) ) content. Photosensitized neoplastic tissue revealed shifted peak position and decreased β-sheet secondary structure of proteins (1,624 cm(-1) ) amount in comparison to non-treated neoplastic lesions. PC-LDA score plots discriminated non-treated neoplastic skin spectra from post-PDT cutaneous lesions with accuracy of 92.8%, whereas non-treated neoplastic

  15. Physiological oxygen concentration alters glioma cell malignancy and responsiveness to photodynamic therapy in vitro.

    Science.gov (United States)

    Albert, Ina; Hefti, Martin; Luginbuehl, Vera

    2014-11-01

    The partial pressure of oxygen (pO2) in brain tumors ranges from 5 to 15%. Nevertheless, the majority of in vitro experiments with glioblastoma multiforme (GBM) cell lines are carried out under an atmospheric pO2 of 19 to 21%. Recently, 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), has been introduced to neurosurgery to allow for photodynamic diagnosis and photodynamic therapy (PDT) in high-grade gliomas. Here, we investigate whether low pO2 affects GBM cell physiology, PpIX accumulation, or PDT efficacy. GBM cell lines (U-87 MG and U-251 MG) were cultured under atmospheric (pO2  =  19%) and physiological (pO2  =  9%) oxygen concentrations. PpIX accumulation and localization were investigated, and cell survival and cell death were observed following in vitro PDT. A physiological pO2 of 9% stimulated GBM cell migration, increased hypoxia-inducible factor (HIF)-1 alpha levels, and elevated resistance to camptothecin in U-87 MG cells compared to cultivation at a pO2 of 19%. This oxygen reduction did not alter 5-ALA-induced intracellular PpIX accumulation. However, physiological pO2 changed the responsiveness of U-87 MG but not of U-251 MG cells to in vitro PDT. Around 20% more irradiation light was required to kill U-87 MG cells at physiological pO2, resulting in reduced lactate dehydrogenase (LDH) release (one- to two-fold) and inhibition of caspase 3 activation. Reduction of oxygen concentration from atmospheric to a more physiological level can influence the malignant behavior and survival of GBM cell lines after in vitro PDT. Therefore, precise oxygen concentration control should be considered when designing and performing experiments with GBM cells.

  16. Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

    Science.gov (United States)

    Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

    2011-02-01

    A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

  17. Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

    Directory of Open Access Journals (Sweden)

    Soo Khee

    2009-11-01

    Full Text Available Abstract Background Photodynamic therapy (PDT is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR, on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors.

  18. INTRAOPERATIVE PHOTODYNAMIC THERAPY IN PATIENT WITH STAGE IIIC BREAST CANCER (8 YEARS WITHOUT RECURRENCE

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2017-01-01

    Full Text Available The article presents  a clinical observation  of the patient  of 38 y.o. with cancer of the left breast stage IIIC урТ4bN3М0L1V1. On the 1st  step of the treatment the patient  had 2 courses of CAF neoadjuvant chemotherapy, on the 2nd  step – extended radical mastectomy on the left with intraoperative photodynamic therapy and closure of the defect with ТRАМ-flap, on the 3rd step – continuation of the chemotherapy (8 courses, on the 4th  step  – radiation  therapy  to the chest wall on the left and zones of regional lymph drainage, targeted therapy  with herceptin  a (1 year. Four years later a silicone implant was inserted  into the left breast. Corrective surgery (reduction  mammoplasty on the right side was performed in april, 2017. Currently, the patient has remission of the disease of the left breast, the period of remission accounts for 8 years. 

  19. Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

    Science.gov (United States)

    Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

    2017-03-28

    Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

  20. Preparation of fluorescent mesoporous hollow silica-fullerene nanoparticles via selective etching for combined chemotherapy and photodynamic therapy

    Science.gov (United States)

    Yang, Yannan; Yu, Meihua; Song, Hao; Wang, Yue; Yu, Chengzhong

    2015-07-01

    Well-dispersed mesoporous hollow silica-fullerene nanoparticles with particle sizes of ~50 nm have been successfully prepared by incorporating fullerene molecules into the silica framework followed by a selective etching method. The fabricated fluorescent silica-fullerene composite with high porosity demonstrates excellent performance in combined chemo/photodynamic therapy.Well-dispersed mesoporous hollow silica-fullerene nanoparticles with particle sizes of ~50 nm have been successfully prepared by incorporating fullerene molecules into the silica framework followed by a selective etching method. The fabricated fluorescent silica-fullerene composite with high porosity demonstrates excellent performance in combined chemo/photodynamic therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02769a

  1. Is Photodynamic Therapy with Adjunctive Non-Surgical Periodontal Therapy Effective in the Treatment of Periodontal Disease under Immunocompromised Conditions

    International Nuclear Information System (INIS)

    Javed, F.; Hezaimi, K.A.; Qadri, T.; Ahmed, H.B.; Corbet, F.E.; Romanos, G.E.

    2013-01-01

    The aim was to assess whether or not photodynamic therapy (PDT) with adjunctive scaling-and-root-planing (SRP) is effective in the treatment of periodontitis under immunocompromised conditions. PubMed/Medline and Google-Scholar databases were searched from 1967 to May 2013 using various key words. Six studies (five experimental and one clinical) were included. In the clinical study, SRP with PDT was reported to be ineffective in treating chronic periodontitis in T2DM patients. All experimental studies reported significantly less bone loss in periodontal defects treated with SRP+PDT than those treated with SRP alone. Efficacy of PDT+SRP in the treatment of periodontal disease under immunocompromised conditions remains unclear. (author)

  2. Is Photodynamic Therapy with Adjunctive Non-Surgical Periodontal Therapy Effective in the Treatment of Periodontal Disease under Immunocompromised Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Javed, F.; Hezaimi, K. A. [King Saud Univ., Riyadh (Saudi Arabia). College of Applied Medical Sciences; Qadri, T. [Karolinska Inst., Huddinge (Sweden). Dept. of Dental Medicine; Ahmed, H. B. [Al-Farabi Dental College, Riyadh (Saudi Arabia). Dept. of Dentistry; Corbet, F. E. [University of Hong Kong, Hong Kong (Hong Kong). Dept. of Periodontology; Romanos, G. E. [Stony Brook University, New York (United States). School of Dental Medicine

    2013-10-15

    The aim was to assess whether or not photodynamic therapy (PDT) with adjunctive scaling-and-root-planing (SRP) is effective in the treatment of periodontitis under immunocompromised conditions. PubMed/Medline and Google-Scholar databases were searched from 1967 to May 2013 using various key words. Six studies (five experimental and one clinical) were included. In the clinical study, SRP with PDT was reported to be ineffective in treating chronic periodontitis in T2DM patients. All experimental studies reported significantly less bone loss in periodontal defects treated with SRP+PDT than those treated with SRP alone. Efficacy of PDT+SRP in the treatment of periodontal disease under immunocompromised conditions remains unclear. (author)

  3. Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris

    DEFF Research Database (Denmark)

    Hædersdal, Merete; Togsverd-Bo, Katrine; Wulf, Hans Chr.

    2008-01-01

    through searches in PubMed and the Cochrane Library. Results A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources...... outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments Udgivelsesdato: 2008/3...

  4. [Effect of M007 mediated photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro].

    Science.gov (United States)

    Zhou, Yu-Kai; Wu, Wen-Zhi; Zhang, Lan; Yang, Chun-Hui; Wang, Yan-Ping

    2012-01-01

    To investigate the effect of a new photosensitizer, M007 mediated photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro. Human osteosarcoma MG63 cells were prepared as 1 x 10(6) /mL single-cell suspension, and 1 mL cells were transferred into 60 mL culture dish, then treated with 5 different gradient dosages (0, 2, 4, 8, 16 micromol/L) of M007 followed by photodynamic therapy or dark reaction for 10 min. The survival rate of the cells and the mode of cell death were detected by flow cytometry with the stain of Annexin V-FITC/PI. The effect on proliferation of survival cells was observed by MTT assay and colony-forming assay. M007 mediated photodynamic therapy induced the inactivation of MG63 human osteosarcoma cells in the way of late apoptosis/necrosis or becoming naked nucleus predominately. More than 90% MG63 cells in M007-PDT group were dead under the treatment of 2-16 micromol/L M007. The survival rates of 4-16 micromol/L M007-PDT group were steadily less than 1%. The optical densities did not increase with extension of culture time in 2-8 micromol/L M007-PDT group (P > 0.05). There were 16 survival alive cells found occasionally in 2 micromol/L M007-PDT group, but no colonies found in other groups. M007 mediated photodynamic therapy totally inactivated human osteosarcoma MG63 cells in vitro with the dosage more than 4 micromol/L.

  5. In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

    2009-01-01

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.

  6. Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways

    Czech Academy of Sciences Publication Activity Database

    Moserová, Irena; Králová, Jarmila

    2012-01-01

    Roč. 7, č. 3 (2012), e32972 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LC06077; GA ČR GA203/09/1311; GA ČR(CZ) GAP303/11/1291 Institutional research plan: CEZ:AV0Z50520514 Keywords : photodynamic therapy * porphyrin derivatives * cell death * ER stress Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  7. Review of photodynamic therapy with 5-methyl aminolevulinate in actinic keratosis, epidermoid carcinoma and basal cell carcinoma

    International Nuclear Information System (INIS)

    Fallas Moya, Said

    2013-01-01

    A bibliographic review was conduced on the use of 5-methyl aminolevulinate in dermatology, specifically in the treatment of actinic keratosis, epidermoid carcinoma and basal cell carcinoma. The basic fundamentals of photodynamic therapy are described. The preparation and method of use of photodynamic therapy with 5-methyl aminolevulinate (MAL-PDT) are detailed. The clinical studies that were realized with photodynamic therapy for the treatment of actinic keratosis, epidermoid carcinoma and basal cell carcinoma are mentioned. Different photo-inducible agents and other current therapeutic options of first-line are compared. The MAL-PDT has have the advantage of to present less side effects and the same have been more tolerable than liquid nitrogen and 5 fluorouracil. The MAL-PDT has been considered as an effective option for the treatment of Bowen's disease. Invasive epidermoid carcinoma has existed without evidence to support the routine use of this therapeutic. For superficial basal cell carcinoma, the MAL-PDT has presented a high cure rate and transient and manageable side effects in extensive and multiple lesions. The MAL-PDT has been an effective and safe treatment in patients with basal cell carcinoma, for those with less depth of 2mm. The MAL-PDT could play an important role in the field of prevention with immunosuppressed patients, particularly, those that have required transplant and its immunosuppression has been pharmacological. The use or not of the MAL-PDT, should be evaluated individually for each patient and to have suitable characteristics for each disease that was cited in this review. The photodynamic therapy with 5-methyl aminolevulinate has been a therapeutic modality of considerable economy, however, it should be evaluated in the context of number of inquiries and side effects that have offered other therapeutic modalities [es

  8. Evaluation of Topical Photodynamic Therapy of Mammary Carcinoma with an Experimental Gel Containing Liposomal Hydroxyl-aluminium Phthalocyanine

    Czech Academy of Sciences Publication Activity Database

    Sutoris, K.; Větvička, D.; Horák, L.; Beneš, J.; Nekvasil, Miloš; Ježek, Petr; Zadinová, M.; Poučková, P.

    2012-01-01

    Roč. 32, č. 9 (2012), s. 3769-3774 ISSN 0250-7005 R&D Projects: GA MPO(CZ) 2A-1TP1/026; GA MŠk(CZ) OE09026; GA TA ČR(CZ) TA01010781 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : photodynamic therapy * phthalocyanine * liposomal sensitizer Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.713, year: 2012

  9. Comparing clinical effects of photodynamic therapy as a novel method with topical corticosteroid for treatment of Oral Lichen Planus.

    Science.gov (United States)

    Bakhtiari, Sedigheh; Azari-Marhabi, Saranaz; Mojahedi, Seyyed Masoud; Namdari, Mahshid; Rankohi, Zahra Elmi; Jafari, Soudeh

    2017-12-01

    Oral lichen planus is an autoimmune disorder with several challenges in treatment. Photodynamic therapy has been proposed as a new treatment option for the disease. The present study compared the clinical effects of photodynamic therapy to dexamethasone mouthwash in the treatment of oral lichen planus lesions. In this randomized clinical trial, 30 patients with oral lichen planus were included.15 patients were treated with 5% methylene blue mediated photodynamic therapy using Fotosan device for 30s (630nm wavelength and 7.2-14.4J/cm 2 dose) for 4 sessions in the days 1, 4, 7, 14. In another group, the treatment was done on 15 patients by 0.5mg tab dexamethasone solution in 5cc water, rinsed 4 times in a day within two weeks. The sign score, symptoms scores (pain), clinical severity and treatment efficacy were measured at the days 15, 30, 60, 90 after beginning of the treatment. The results were subjected to Mann-whitney U test in both groups. No significant difference existed between the two modalities regarding the treatment efficacy index, sign score, symptom score and clinical severity on the 15, 30, 60 and 90 post-treatment days. Decreases in patient's symptoms were statistically significant in both groups. Photodynamic therapy was as effective as the dexamethasone mouth wash in the treatment of oral lichen planus. It could be used as a safe modality in the treatment of oral lichen planus lesions without identified side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Photodynamic therapy for angiosarcoma of scalp as alternative approach for surgical treatment in patient with severe co-morbidity

    Directory of Open Access Journals (Sweden)

    E. V. Yaroslavtseva-Isaeva

    2014-01-01

    Full Text Available A case of successful photodynamic therapy in patient of 86 y.o. with diagnosis: angiosarcoma of right temporal-parietal region stage IIA (Т2вN0M0 is reported. The tumor was as soft tissue round shape lesion with tuberous contours 3.4х3.4х1.1 cm in size, located in subcutaneous tissue in right parietal region with no scull bone invasion. The patient was refused to surgical treatment with general anesthesia due to severe cardiovascular co-morbidity. The patient underwent a course of photodynamic therapy with Photolon. The photosensitizer was intravenousely introduced for 3 h before irradiation at dose of 1 mg/kg body weight. The parameters of irradiation were as follows: output power – 0.8 W, light dose – 150 J/cm2, 4 irradiation fields 2.5 cm in diameter. During the irradiation there were moderate pain which did not require drug management. After PDT complete regression of the tumor was achieved. For nowadays (11 months after treatment the patient is observed with no recurrence. The reported case shows that photodynamic therapy may be successfully used for alternative treatment of soft tissue angiosarcoma in patients with no ability for surgical treatment. 

  11. Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Chen Zhi-Long

    2009-01-01

    Full Text Available Abstract As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl-13,17-bis-(3-hydroxypropyl porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4 and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.

  12. Synthesis and characterization of a new class of glycosylated porphyrins bearing the RGD moiety and their application in photodynamic therapy

    International Nuclear Information System (INIS)

    Chaleix, Vincent

    2003-01-01

    The use of porphyrins and analogues as photosensitisers together with visible light is a new treatment of tumors (photodynamic therapy, PDT). Carbohydrate-substituted porphyrins are in this domain very promising compounds. In addition, it is known that endothelial cells of the neo-vascularisation in tumors express αVβ3 integrin. Extracellular domains of this transmembrane glycoprotein are able to bind components of the extracellular matrix (ECM) and more precisely the sequence Arg-Gly-Asp. With the aim of their utilization in photodynamic therapy of cancers, we describe the synthesis and characterization (UV-Visible, mass, NMR) of new glucosylated porphyrins bearing the RGD moiety. The first synthesised compounds were derived from tritolyl and tri-glucosyl-aryl-porphyrins where the peptidic moiety is linked to the phenyl group by a spacer arm by means of a solid phase reaction.. The second series consists of glucosylated porphyrin derivatives bearing a cyclical unsaturated pentapeptide including RGD sequence, obtained by ring closing metathesis in solid phase. We have also synthesized a dimer in which the two glucosylated porphyrins are linked by the RGD sequence. These compounds produced 1 O 2 and photo-cyto-toxicities against K562 leukemia cell line were favourably compared to Photofrin II R . Due to their sensitising abilities, these compounds are of considerable interest for photodynamic therapy. (author) [fr

  13. Afterglow properties of CaF{sub 2}:Tm nanoparticles and its potential application in photodynamic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zahedifar, M., E-mail: zhdfr@kashanu.ac.ir [Physics Department, University of Kashan, Kashan, I.R. Iran (Iran, Islamic Republic of); Institute of Nanoscience and Nanotechniology, University of Kashan, Kashan, I.R. Iran (Iran, Islamic Republic of); Sadeghi, E. [Physics Department, University of Kashan, Kashan, I.R. Iran (Iran, Islamic Republic of); Institute of Nanoscience and Nanotechniology, University of Kashan, Kashan, I.R. Iran (Iran, Islamic Republic of); Shanei, M.M. [Institute of Nanoscience and Nanotechniology, University of Kashan, Kashan, I.R. Iran (Iran, Islamic Republic of); Sazgarnia, A. [Research Center and Department of Medical Physics, School of Medicine, Mashhad University of Medical Sciences, Vakil Abad Blvd., Mashhad (Iran, Islamic Republic of); Mehrabi, M. [Institute of Nanoscience and Nanotechniology, University of Kashan, Kashan, I.R. Iran (Iran, Islamic Republic of)

    2016-03-15

    CaF{sub 2}:Tm nanoparticles (NPs) were synthesized by the hydrothermal method. Intense afterglow emission with long life time was found for the produced NPs, so its applicability in photodynamic therapy was investigated. Since the wavelength of the afterglow emission of the NPs fairly matches with the absorption band of the PpIX sensitizer, especially in the red region, the Cystein mediator was used to bond NPs with the PpIX sensitizer. The CaF{sub 2}:Tm NPs conjugated with PpIX was exposed to X-ray and by using the Antracene as detector, the production of the singlet oxygen was verified. Therefore, the produced NPs are recommended as a source of energy that improves photodynamic therapy beyond its current limitations. - Highlights: • Intense afterglow emission found for the synthesized CaF{sub 2}:Tm nanoparticles. • CaF{sub 2}:Tm emission band fairly matched with PpIX sensitizer's absorption band. • CaF{sub 2}:Tm conjugated with the sensitized is a good candidate for photodynamic therapy. • The application of nanoparticles in producing singlet oxygen was verified.

  14. Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical model in the dog.

    Science.gov (United States)

    Ross, H M; Smelstoys, J A; Davis, G J; Kapatkin, A S; Del Piero, F; Reineke, E; Wang, H; Zhu, T C; Busch, T M; Yodh, A G; Hahn, S M

    2006-10-01

    Local recurrence of rectal cancer remains a significant clinical problem despite multi-modality therapy. Photodynamic Therapy (PDT) is a cancer treatment which generates tumor kill through the production of singlet oxygen in cells containing a photosensitizing drug when exposed to laser light of a specific wavelength. PDT is a promising modality for prevention of local recurrence of rectal cancer for several reasons: tumor cells may selectively retain photosensitizer at higher levels than normal tissues, the pelvis after mesorectal excision is a fixed space amenable to intra-operative illumination, and PDT can generate toxicity in tissues up to 1 cm thick. This study evaluated the safety, tissue penetration of 730 nm light, normal tissue toxicity and surgical outcome in a dog model of rectal resection after motexafin lutetium-mediated photodynamic therapy. Ten mixed breed dogs were used. Eight dogs underwent proctectomy and low rectal end to end stapled anastomosis. Six dogs received the photosensitizing agent motexafin lutetium (MLu, Pharmacyclics, Inc., Sunnyvale, CA) of 2 mg/kg preoperatively and underwent subsequent pelvic illumination of the transected distal rectum of 730 nm light with light doses ranging from 0.5 J/cm(2) to 10 J/cm(2) three hours after drug delivery. Two dogs received light, but no drug, and underwent proctectomy and low-rectal stapled anastomosis. Two dogs underwent midline laparotomy and pelvic illumination. Light penetration in tissues was determined for small bowel, rectum, pelvic sidewall, and skin. Clinical outcomes were recorded. Animals were sacrificed at 14 days and histological evaluation was performed. All dogs recovered uneventfully. No dog suffered an anastomotic leak. Severe tissue toxicity was not seen. Histological findings at necropsy revealed mild enteritis in all dogs. The excitation light penetration depths were 0.46 +/- 0.18, 0.46 +/- 0.15, and 0.69 +/- 0.39 cm, respectively, for rectum, small bowel, and peritoneum in

  15. A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

    Science.gov (United States)

    Yokoyama, Yoshihito; Shigeto, Tatsuhiko; Miura, Rie; Kobayashi, Asami; Mizunuma, Makito; Yamauchi, Aisa; Futagami, Masayuki; Mizunuma, Hideki

    2016-01-01

    The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

  16. Photodynamic antimicrobial chemotherapy for Staphylococcus aureus and multidrug-resistant bacterial burn infection in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Mai B

    2017-08-01

    Full Text Available Bingjie Mai,1,2 Yiru Gao,1,2 Min Li,1,2 Xiaobing Wang,1,2 Kun Zhang,1,2 Quanhong Liu,1,2 Chuanshan Xu,3 Pan Wang1,2 1Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, 2National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an, 3School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China Background and objectives: Antibiotic resistance has emerged as one of the most important determinants of outcome in patients with serious infections, along with the virulence of the underlying pathogen. Photodynamic antimicrobial chemotherapy (PACT has been proposed as an alternative approach for the inactivation of bacteria. This study aims to evaluate the antibacterial effect of sinoporphyrin sodium (DVDMS-mediated PACT on Staphylococcus aureus and multidrug resistant S. aureus in vitro and in vivo.Materials and methods: Bacteria were incubated with DVDMS and exposed to treatment with light. After PACT treatment, colony-forming units were counted to estimate the bactericidal effect. Intracellular reactive oxygen-species production was detected by flow cytometry. Flow cytometry and fluorescence-microscopy detection of bacterial cell-membrane permeability. Enzyme-linked immunosorbent assays were used to determine expression of VEGF, TGFβ1, TNFα, IL6, and bFGF factors in burn infection.Results: DVDMS-PACT effectively killed bacterial proliferation. Intracellular ROS levels were enhanced obviously in the PACT-treatment group. SYTO 9 and propidium iodide staining showed a decrease in the ratio of green:red fluorescence intensity in the PACT-treatment group in comparison to the control group. Enzyme-linked immunosorbent-assay results revealed that in the healing process, the expression of bFGF, TGFβ1, and VEGF in the treatment group were higher than in the control group

  17. Modifications of cell cycle according to conditions of photodynamic therapy induced by hypericin

    International Nuclear Information System (INIS)

    Mikes, J.; Kleban, J.; Szilardiova, B.; Sackova, V; Fedorocko, P.; Horvath, V.; Brezani, P.

    2004-01-01

    Photodynamic therapy (PDT) is becoming a rapidly developing method in cancer therapy, recently. PDT is based on administration of nontoxic/weakly toxic photosensitive compound and its activation with light of appropriate wave length. Although PDT is of use in clinical practise, new promising photosensitive compounds with advantageous attributes are discovered continuously. Hypericin, one of these compounds, is known to induce cell cycle arrest in G 2 /M phase at low doses. This arrest is caused by microtubules destruction linked to Bcl-2 phosphorylation as a consequence of CDK-1/cyclin B1 complex activation, but data about combinations of different hypericin concentrations and light doses are missing. PDT effect is effected by multiple factors. In our experiment, we have been shown, by cytokinetical and flow-cytometric analysis, the way how the cells response to photo-cytotoxic effect of hypericin. By combination of two factors, light doses and concentrations of hypericin, we eliminated inappropriate combinations and chose for another analysis narrow ranges of both factors. We discovered a breakpoint between a controlled cell death - apoptosis and cell signalling disaster followed by necrosis. (authors)

  18. An in vivo photodynamic therapy with diode laser to cell activation of kidney dysfunction

    International Nuclear Information System (INIS)

    Astuti, Suryani Dyah; Prasaja, Brahma Indra; Prijo, Tri Anggono

    2017-01-01

    This study aims to analyze the effect of photodynamic therapy (PDT) low level laser therapy (LLLT) 650 nm in the experimental animals mice ( Musmuculus ) suffering from kidney organ damage in mice ( Musmuculus ) in vivo. Exposure laser acupuncture was performed on the kidney BL-23. The conditioning of kidney damage in mice used carbofuraan 35 at a dose of 0.041697 mg/mice. LLLT 650 nm exposure was done on a wide variety of energy (0.5; 1.0; 1.5; 2.0; 4.0; 5.0; 6.0; 7.0) J. The histopathological kidney cells in mice renal impairment showed that exposure to 650 nm laser energy 1 Joule resulted in the reduction of damaged cells (necrosis) and normal cells were increased with the improvement of renal tubular cells (64.14 ± 8:02)%. Therefore, exposure to 650 nm LLLT on acupuncture points Shenshu (BL-23) has the ability to proliferation of renal tubular cells of mice. (paper)

  19. Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

    International Nuclear Information System (INIS)

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2010-01-01

    Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

  20. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Paola Savoia

    2015-09-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer in individuals with fair skin type (I–II and steadily increasing in incidence (70% of skin malignancy. It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC.

  1. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Science.gov (United States)

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  2. Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts.

    Science.gov (United States)

    Hu, Zhili; Liu, Lishi; Zhang, Wenjing; Liu, Hui; Li, Junpeng; Jiang, Lifen; Zeng, Kang

    2018-03-01

    Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy.

    Science.gov (United States)

    Wan, Guoyun; Chen, Bowei; Li, Ling; Wang, Dan; Shi, Shurui; Zhang, Tao; Wang, Yue; Zhang, Lianyun; Wang, Yinsong

    2018-02-01

    Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer. Compared to free ICG, ICG and DOX co-loaded RAs (DIRAs) exhibited nearly identical PTT efficiency both in vitro and in vivo, but meanwhile their PDT efficiency was enhanced significantly. In mouse breast cancer cells, DIRAs significantly inhibited cell growth and induced cell apoptosis after laser irradiation. In breast tumor-bearing mice, intratumoral injection of DIRAs and followed by local laser irradiation almost completely ablated breast tumor and further suppressed tumor recurrence and metastasis. In conclusion, this biomimetic multifunctional nanosystem can facilitate breast cancer treatment by combining PTT/PDT and chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis?

    Science.gov (United States)

    Kessels, Janneke P H M; Nelemans, Patty J; Mosterd, Klara; Kelleners-Smeets, Nicole W J; Krekels, Gertruud A M; Ostertag, Judith U

    2016-03-01

    Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; -2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo.

  5. Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update and expansion.

    Science.gov (United States)

    Ross, Kate; Cherpelis, Basil; Lien, Mary; Fenske, Neil

    2013-12-01

    Topical photodynamic therapy (PDT) is an option for the treatment of cutaneous malignancy. To present an update and expansion on a previous review of the use of PDT in the current literature in the treatment of actinic keratoses (AK), superficial and nodular basal cell carcinoma (sBCC, nBCC), squamous cell carcinoma (SCC), Bowen's disease, cutaneous T cell lymphoma (CTCL), malignant melanoma, and its use in chemoprevention. Extensive PubMed search January 2013. We find sufficient evidence to recommend the use of PDT in certain patients in the treatment of AK, Bowen's disease, sBCC, and nBCC. It is especially useful in those with contraindications to surgery, widespread areas of involvement, and large lesions. Not only can it be considered superior to other therapies as far as recovery time, tolerance, and cosmetic outcomes, but it also should be considered, when indicated, as first-line treatment in the above conditions. Investigations continue for the use of PDT in the treatment of melanoma, SCC, chemoprevention, and CTCL. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  6. Effects of the photodynamic therapy on microbial reduction of diabetic ulcers in humans

    Science.gov (United States)

    Carrinho Aureliano, Patrícia Michelassi; Andreani, Dora Inés. Kozusny; Morete, Vislaine de Aguiar; Iseri Giraldeli, Shizumi; Baptista, Alessandra; Navarro, Ricardo Scarparo; Villaverde, Antonio Balbin

    2018-02-01

    Diabetes Mellitus is a chronic disease that can lead to lower-limb ulceration. The photodynamic therapy (PDT) is based on light interaction with a photosensitizer capable to promote bacterial death and tissue repair acceleration. This study analyzed the effects of PDT in the repair of human diabetic ulcers, by means of microbiological assessment. The clinical study was composed of 12 patients of both sexes with diabetic ulcers in lower limbs that were divided into two groups, control group (n=6) and PDT group (n=6). All patients were treated with collagenase/chloramphenicol during the experimental period, in which 6 of them have received PDT with methylene blue dye (0.01%) associated with laser therapy (660 nm), dose of 6 J/cm2¨ and 30 mW laser power. PDT group received ten treatment sessions. Wounds were evaluated for micro-organisms analysis. It was found a reduction in the occurrence of Staphylococcus aureus in both groups, being that reduction more pronounced in the PDT group. Microbial count was performed on PDT group, showing a statistical difference reduction (p<0.05) when compared before and after the treatment. It is concluded that PDT seems to be effective in microbial reduction of human diabetic wounds, promoting acceleration and improvement of tissue repair quality.ty.

  7. Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

    Science.gov (United States)

    Nair, Lakshmi V; Nazeer, Shaiju S; Jayasree, Ramapurath S; Ajayaghosh, Ayyappanpillai

    2015-06-23

    Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 μg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC.

  8. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Photodynamic therapy in neurosurgery: a proof of concept of treatment planning system

    Science.gov (United States)

    Dupont, C.; Reyns, N.; Mordon, S.; Vermandel, M.

    2017-02-01

    Glioblastoma (GBM) is the most common primary brain tumor. PhotoDynamic Therapy (PDT) appears as an interesting research field to improve GBM treatment. Nevertheless, PDT cannot fit into the current therapeutic modalities according to several reasons: the lack of reliable and reproducible therapy schemes (devices, light delivery system), the lack of consensus on a photosensitizer and the absence of randomized and controlled multicenter clinical trial. The main objective of this study is to bring a common support for PDT planning. Here, we describe a proof of concept of Treatment Planning System (TPS) dedicated to interstitial PDT for GBM treatment. The TPS was developed with the integrated development environment C++ Builder XE8 and the environment ArtiMED, developed in our laboratory. This software enables stereotactic registration of DICOM images, light sources insertion and an accelerated CUDA GPU dosimetry modeling. Although, Monte-Carlo is more robust to describe light diffusion in biological tissue, analytical model accelerated by GPU remains relevant for dose preview or fast reverse planning processes. Finally, this preliminary work proposes a new tool to plan interstitial or intraoperative PDT treatment and might be included in the design of future clinical trials in order to deliver PDT straightforwardly and homogenously in investigator centers.

  10. Optical spectroscopy of radiotherapy and photodynamic therapy responses in normal rat skin shows vascular breakdown products

    Science.gov (United States)

    Teles de Andrade, Cintia; Nogueira, Marcelo S.; Kanick, Stephen C.; Marra, Kayla; Gunn, Jason; Andreozzi, Jacqueline; Samkoe, Kimberley S.; Kurachi, Cristina; Pogue, Brian W.

    2016-03-01

    Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.

  11. Endoscopic surgery and photodynamic therapy for behign and malignant neoplasms of colon

    Directory of Open Access Journals (Sweden)

    А. А. Razzhivina

    2013-01-01

    Full Text Available The review of literature for current methods of endoscopic treatment for colon epithelial neoplasms is represented. Such types of endoscopic interventions as loop electroresection, submucosal dissection, coagulation and destruction of tumors and combination of several options depending on efficiency of previous therapy is analyzed. Limitations of every method, its special aspects and possible complications are described. Special focus is on specifics of neoplasms for which selected methods may be the most effective. Thus, hot biopsy and destruction using high-energy laser is efficient for small flat neoplasms, endoscopic electroexcision – far small pedunculated lesions, and fragmentation is adequate for exophytic tumors more than 2.0 cm. Long-term results of endoscopic treatment, recurrence rates after different options are represented. The literature for photodynamic therapy consists mostly articles about development (on pre-clenecal stage of new photosensitizers which are effective for colon cancer, new methods of treatment including combination with hyperthermia in low-dose light irradiation etc. The literature data shows the prospectivity of subsequent developments in this field. 

  12. An in vivo photodynamic therapy with diode laser to cell activation of kidney dysfunction

    Science.gov (United States)

    Dyah Astuti, Suryani; Indra Prasaja, Brahma; Anggono Prijo, Tri

    2017-05-01

    This study aims to analyze the effect of photodynamic therapy (PDT) low level laser therapy (LLLT) 650 nm in the experimental animals mice (Musmuculus) suffering from kidney organ damage in mice (Musmuculus) in vivo. Exposure laser acupuncture was performed on the kidney BL-23. The conditioning of kidney damage in mice used carbofuraan 35 at a dose of 0.041697 mg/mice. LLLT 650 nm exposure was done on a wide variety of energy (0.5; 1.0; 1.5; 2.0; 4.0; 5.0; 6.0; 7.0) J. The histopathological kidney cells in mice renal impairment showed that exposure to 650 nm laser energy 1 Joule resulted in the reduction of damaged cells (necrosis) and normal cells were increased with the improvement of renal tubular cells (64.14 ± 8:02)%. Therefore, exposure to 650 nm LLLT on acupuncture points Shenshu (BL-23) has the ability to proliferation of renal tubular cells of mice.

  13. Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

    2005-01-01

    In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

  14. Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy

    Science.gov (United States)

    Broekgaarden, Mans; Kos, Milan; Jurg, Freek A.; van Beek, Adriaan A.; van Gulik, Thomas M.; Heger, Michal

    2015-01-01

    Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor κB (NF-κB) has been identified as a potential pharmacological target, albeit inhibition of NF-κB may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-κB in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-κB in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells. PMID:26307977

  15. The quest for optimal antimicrobial therapy

    NARCIS (Netherlands)

    Mol, Petrus Gerardus Maria

    2005-01-01

    Since the discovery of sulphonam ides and penicillin in the 1930's, and their widespread use in clinical practice during World War II a plethora of new antimicrobial agents have entered the market. Initial optim ism has faded that these new drugs would eliminate infectious diseases as killer

  16. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    Chen Bin; Pogue, Brian W.; Hoopes, P. Jack; Hasan, Tayyaba

    2005-01-01

    Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm 2 ) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm 2 ) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments

  17. The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Theodossis A. Theodossiou

    2017-08-01

    Full Text Available The diverse responses of different cancers to treatments such as photodynamic therapy of cancer (PDT have fueled a growing need for reliable predictive markers for treatment outcome. In the present work we have studied the differential response of two phenotypically and genotypically different breast adenocarcinoma cell lines, MCF7 and MDA-MB-231, to hypericin PDT (HYP-PDT. MDA-MB-231 cells were 70% more sensitive to HYP PDT than MCF7 cells at LD50. MCF7 were found to express a substantially higher level of glutathione peroxidase (GPX4 than MDA-MB-231, while MDA-MB-231 differentially expressed glutathione-S-transferase (GSTP1, mainly used for xenobiotic detoxification. Eighty % reduction of intracellular glutathione (GSH by buthionine sulfoximine (BSO, largely enhanced the sensitivity of the GSTP1 expressing MDA-MB-231 cells to HYP-PDT, but not in MCF7 cells. Further inhibition of the GSH reduction however by carmustine (BCNU resulted in an enhanced sensitivity of MCF7 to HYP-PDT. HYP loading studies suggested that HYP can be a substrate of GSTP for GSH conjugation as BSO enhanced the cellular HYP accumulation by 20% in MDA-MB-231 cells, but not in MCF7 cells. Studies in solutions showed that L-cysteine can bind the GSTP substrate CDNB in the absence of GSTP. This means that the GSTP-lacking MCF7 may use L-cysteine for xenobiotic detoxification, especially during GSH synthesis inhibition, which leads to L-cysteine build-up. This was confirmed by the lowered accumulation of HYP in both cell lines in the presence of BSO and the L-cysteine source NAC. NAC reduced the sensitivity of MCF7, but not MDA-MB-231, cells to HYP PDT which is in accordance with the antioxidant effects of L-cysteine and its potential as a GSTP substrate. As a conclusion we have herein shown that the different GSH based cell defense mechanisms can be utilized as predictive markers for the outcome of PDT and as a guide for selecting optimal combination strategies. Keywords

  18. Photodynamic therapy as a local therapeutic adjunct for the treatment of vertebral metastases

    Science.gov (United States)

    Yee, Albert; Burch, Shane; Akens, Margarete; Won, Emily; Lo, Victor; Wise-Milestone, Lisa; Bisland, Stuart; Theriault, Aimee; Niu, Carolyn; Wilson, Brian C.; Whyne, Cari

    2013-03-01

    Metastatic cancer causes the majority of tumors in bone, most frequently detected in the spinal column. Skeletal complications cause pain and neurologic impairment. Photodynamic therapy (PDT) has been used to treat a variety of cancers. Minimally invasive surgical (MIS) strategies may allow targeted light application essential for PDT within bone structures. The purpose of this manuscript is to provide an update on pre-clinical status as well as early clinical experience of a Phase I clinical trial on vertebral PDT. A pre-clinical (rnu/rnu rat) vertebral metastasis model of osteolytic (MT-1 breast cancer) was optimized and used to evaluate the effect of vertebral PDT. PDT alone and in combination with other standard local (radiation therapy, RT) and systemic (bisphosphonates, BP) therapies was evaluated through bioluminescence imaging, micro-CT based stereology, histology, and biomechanical testing. Single PDT treatment (photosensitizer BPD-MA, 690nm light) ablated tumor tissue in targeted vertebrae. PDT led to significant increases in bone structural properties, with greatest benefits observed from combined BP+PDT therapy: 76% and 19% increases in bone volume fraction in treated tumor-bearing and healthy untreated controls, respectively. Similar synergistic improvements (but of lesser magnitude) were found in combined PDT+RT treatments. The safety and feasibility of MIS+PDT were evaluated in scale-up animal studies, refining surgical technique for clinical translation. Following appropriate institutional review board as well as Health Canada approval, 5 patients (light only control group) have undergone protocoled treatment to date. These patients have guided further refinement of human therapeutic application from a laser delivery and vertebral bone access perspective.

  19. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

    Science.gov (United States)

    Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2009-02-01

    Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

  20. Investigation into the susceptibility of Burkholderia cepacia complex isolates to photodynamic antimicrobial chemotherapy (PACT)

    Science.gov (United States)

    Cassidy, C. M.; Watters, A. L.; Donnelly, R. F.; Tunney, M. M.

    2009-06-01

    The main cause of morbidity and mortality in cystic fibrosis (CF) sufferers is progressive pulmonary damage caused by recurrent and often unremitting respiratory tract infection. Causative organisms include Pseudomonas aeruginosa and Haemophilus influenzae, but in recent years the Burkholderia cepacia complex has come to the fore. This group of highly drug-resistant Gram-negative bacteria are associated with a rapid decline in lung function and the often fatal cepacia syndrome, with treatment limited to patient segregation and marginally effective antibacterial regimens. Thus, development of an effective treatment is of the upmost importance. PACT, a non-target specific therapy, has proven successful in killing both Gram-positive and Gram-negative bacteria. In this study, planktonic cultures of six strains of the B. cepacia complex were irradiated (635 nm, 200 J cm-2,10 minutes irradiation) following 30 seconds incubation with methylene blue (MB) or meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Rates of kill of > 99 % were achieved with MB- and TMP-PACT. A MB concentration of 50 μg ml-1 and TMP concentration of 500 μg ml-1 were associated with highest percentage kills for each photosensitizer. PACT is an attractive option for treatment of B.cepacia complex infection. Further study, involving biofilm culture susceptibility, delivery of light to the target and in vivo testing will be necessary before it PACT becomes a viable treatment option for CF patients who are colonised or infected with B. cepacia complex.

  1. Tooth color change caused by photosensitizers after photodynamic therapy: An in vitro study.

    Science.gov (United States)

    Costa, Larissa Menezes; Matos, Felipe de Souza; Correia, Ayla Macyelle de Oliveira; Carvalho, Nayane Chagas; Faria-E-Silva, André Luís; Paranhos, Luiz Renato; Ribeiro, Maria Amália Gonzaga

    2016-07-01

    This study aimed to perform an in vitro evaluation of the effect of photosensitizers used in photodynamic therapy (PDT) on tooth color change when used in combination with conventional endodontic treatment. Forty extracted human mandibular premolars were accessed and underwent root canal therapy and PDT. Photosensitizers were used in accordance with the experimental groups: MB (n=10) - PDT with Methylene Blue at 0.01%; TB (n=10) - PDT with Toluidine Blue at 0.01%; MG (n=10) - PDT with Malachite Green at 0.01%, at the concentration of 0.1mg/mL; and PC (n=10) - positive control, PDT with Endo-PTC cream stained with Methylene Blue at 25%. The samples were irradiated with 660-nm diode laser by means of a 330-μm-diameter optical fiber cable at a power density of 40mW for 120s. After light curing, the photosensitizers were removed from the specimens with 10mL sodium hypochlorite at 1%. A reflectance spectrometer was used for evaluation of color prior to and 60days after the experimental procedure based on the CIE L*a*b* system. According to ANOVA test, there were statistically significant differences between the experimental groups (p=0.003). Tukey's test showed a significant difference between PC and TB (p=0.008), as well as between MG and TB (p=0.009). However, there was no statistically significant difference between PC, MG (p=0.957) and MB (p=0.103). It was concluded that the use of PDT as an adjuvant to root canal therapy, using different photosensitizers, led to color change in tooth structure. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Photodynamic therapy as an adjunct to non-surgical periodontal treatment: a randomized, controlled clinical trial.

    Science.gov (United States)

    Christodoulides, Nicos; Nikolidakis, Dimitris; Chondros, Panagiotis; Becker, Jürgen; Schwarz, Frank; Rössler, Ralf; Sculean, Anton

    2008-09-01

    Recent preclinical and clinical data have suggested a potential benefit of photodynamic therapy (PDT) in the treatment of periodontitis. However, there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis. The aim of this study was to evaluate the clinical and microbiologic effects of the adjunctive use of PDT to non-surgical periodontal treatment. Twenty-four subjects with chronic periodontitis were randomly treated with scaling and root planing followed by a single episode of PDT (test) or scaling and root planing alone (control). Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depth (PD), gingival recession, and clinical attachment level (CAL) were measured at baseline and 3 and 6 months after therapy. Primary outcome variables were changes in PD and CAL. Microbiologic evaluation of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia (previously T. forsythensis), Treponema denticola, Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros), Fusobacterium nucleatum, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, and Capnocytophaga spp. was performed at baseline and 3 and 6 months following therapy by using a commercially available polymerase chain reaction test. At 3 and 6 months after treatment, there were no statistically significant differences between the groups with regard to CAL, PD, FMPS, or microbiologic changes. At 3 and 6 months, a statistically significantly greater improvement in FMBS was found in the test group. The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PD reduction and CAL gain, but it resulted in a significantly higher reduction in bleeding scores compared to scaling and root planing alone.

  3. Phosphorus dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer-photosensitizer complexes: Cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue.

    Science.gov (United States)

    Dabrzalska, Monika; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2015-08-15

    Dendrimers due to their unique architecture may play an important role in drug delivery systems including chemotherapy, gene therapy and recently, photodynamic therapy as well. We investigated two dendrimer-photosensitizer systems in context of potential use of these systems in photodynamic therapy. The mixtures of an anionic phosphorus dendrimer of the second generation and methylene blue were studied by UV-vis spectroscopy while that of a cationic phosphorus dendrimer (third generation) and rose bengal were investigated by spectrofluorimetric methods. Spectroscopic analysis of these two systems revealed the formation of dendrimer-photosensitizer complexes via electrostatic interactions as well as π stacking. The stoichiometry of the rose bengal-cationic dendrimer complex was estimated to be 7:1 and 9:1 for the methylene blue-anionic dendrimer complex. The results suggest that these polyanionic or polycationic phosphorus dendrimers can be promising candidates as carriers in photodynamic therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Photodynamic therapy targeting neuropilin-1: Interest of pseudopeptides with improved stability properties.

    Science.gov (United States)

    Thomas, Noémie; Pernot, Marlène; Vanderesse, Régis; Becuwe, Philippe; Kamarulzaman, Ezatul; Da Silva, David; François, Aurélie; Frochot, Céline; Guillemin, François; Barberi-Heyob, Muriel

    2010-07-15

    The general strategy developed aims to favor the vascular effect of photodynamic therapy by targeting tumor vasculature. Since angiogenic endothelial cells represent an interesting target to potentiate this vascular effect, we previously described the conjugation of a photosensitizer to a peptide targeting neuropilins (NRPs) over-expressed specially in tumor angiogenic vessels and we recently characterized the mechanism of photosensitization-induced thrombogenic events. Nevertheless, in glioma-bearing nude mice, we demonstrated that the peptide moiety was degraded to various rates according to time after intravenous administration. In this study, new peptidases-resistant pseudopeptides were tested, demonstrating a molecular affinity for NRP-1 and NRP-2 recombinant chimeric proteins and devoid of affinity for VEGF receptor type 1 (Flt-1). To argue the involvement of NRP-1, MDA-MB-231 breast cancer cells were used, strongly over-expressing NRP-1 receptor. We evidenced a statistically significant decrease of the different peptides-conjugated photosensitizers uptake after RNA interference-mediated silencing of NRP-1. Peptides-conjugated photosensitizers allowed a selective accumulation into cells. In mice, no degradation was observed in plasma in vivo 4h after intravenous injection by MALDI-TOF mass spectrometry. This study draws attention to this potential problem with peptides, especially in the case of targeting strategies, and provides useful information for the future design of more stable molecules. 2010 Elsevier Inc. All rights reserved.

  5. Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

    Science.gov (United States)

    Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2016-01-01

    This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

  6. Glycolytic inhibitors 2-deoxyglucose and 3-bromopyruvate synergize with photodynamic therapy respectively to inhibit cell migration.

    Science.gov (United States)

    Feng, Xiaolan; Wang, Pan; Liu, Quanhong; Zhang, Ting; Mai, Bingjie; Wang, Xiaobing

    2015-06-01

    Most cancer cells have the specially increased glycolytic phenotype, which makes this pathway become an attractive therapeutic target. Although glycolytic inhibitor 2-deoxyglucose (2-DG) has been demonstrated to potentiate the cytotoxicity of photodynamic therapy (PDT), the impacts on cell migration after the combined treatment has never been reported yet. The present study aimed to analyze the influence of glycolytic inhibitors 2-DG and 3-bromopyruvate (3-BP) combined with Ce6-PDT on cell motility of Triple Negative Breast Cancer MDA-MB-231 cells. As determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium-bromide-Tetraz-olium (MTT) assay, more decreased cell viability was observed in 2-DG + PDT and 3-BP + PDT groups when compared with either monotherapy. Under optimal conditions, synergistic potentiation on cell membrane destruction and the decline of cell adhesion and cells migratory ability were observed in both 2-DG + PDT and 3-BP + PDT by electron microscope observation (SEM), wound healing and trans-well assays. Besides, serious microfilament network collapses as well as impairment of matrix metalloproteinases-9 (MMP-9) were notably improved after the combined treatments by immunofluorescent staining. These results suggest that 2-DG and 3-BP can both significantly potentiated Ce6-PDT efficacy of cell migration inhibition.

  7. Treatment planning using tailored and standard cylindrical light diffusers for photodynamic therapy of the prostate

    International Nuclear Information System (INIS)

    Rendon, Augusto; Lilge, Lothar; Beck, J Christopher

    2008-01-01

    Interstitial photodynamic therapy (PDT) has seen a rebirth, partially prompted by the development of photosensitizers with longer absorption wavelengths that enable the treatment of larger tissue volumes. Here, we study whether using diffusers with customizable longitudinal emission profiles, rather than conventional ones with flat emission profiles, improves our ability to conform the light dose to the prostate. We present a modified Cimmino linear feasibility algorithm to solve the treatment planning problem, which improves upon previous algorithms by (1) correctly minimizing the cost function that penalizes deviations from the prescribed light dose, and (2) regularizing the inverse problem. Based on this algorithm, treatment plans were obtained under a variety of light delivery scenarios using 5-15 standard or tailored diffusers. The sensitivity of the resulting light dose distributions to uncertainties in the optical properties, and the placement of diffusers was also studied. We find that tailored diffusers only marginally outperform conventional ones in terms of prostate coverage and rectal sparing. Furthermore, it is shown that small perturbations in optical properties can lead to large changes in the light dose distribution, but that those changes can be largely corrected with a simple light dose re-normalization. Finally, we find that prostate coverage is only minimally affected by small changes in diffuser placement. Our results suggest that prostate PDT is not likely to benefit from the use of tailored diffusers. Other locations with more complex geometries might see a better improvement

  8. Water-Insoluble Photosensitizer Nanocolloids Stabilized by Supramolecular Interfacial Assembly towards Photodynamic Therapy

    Science.gov (United States)

    Liu, Yamei; Ma, Kai; Jiao, Tifeng; Xing, Ruirui; Shen, Guizhi; Yan, Xuehai

    2017-02-01

    Nanoengineering of hydrophobic photosensitizers (PSs) is a promising approach for improved tumor delivery and enhanced photodynamic therapy (PDT) efficiency. A variety of delivery carriers have been developed for tumor delivery of PSs through the enhanced permeation and retention (EPR) effect. However, a high-performance PS delivery system with minimum use of carrier materials with excellent biocompatibility is highly appreciated. In this work, we utilized the spatiotemporal interfacial adhesion and assembly of supramolecular coordination to achieve the nanoengineering of water-insoluble photosensitizer Chlorin e6 (Ce6). The hydrophobic Ce6 nanoparticles are well stabilized in a aqueous medium by the interfacially-assembled film due to the coordination polymerization of tannic acid (TA) and ferric iron (Fe(III)). The resulting Ce6@TA-Fe(III) complex nanoparticles (referenced as Ce6@TA-Fe(III) NPs) significantly improves the drug loading content (~65%) and have an average size of 60 nm. The Ce6@TA-Fe(III) NPs are almost non-emissive as the aggregated states, but they can light up after intracellular internalization, which thus realizes low dark toxicity and excellent phototoxicity under laser irradiation. The Ce6@TA-Fe(III) NPs prolong blood circulation, promote tumor-selective accumulation of PSs, and enhanced antitumor efficacy in comparison to the free-carrier Ce6 in vivo evaluation.

  9. Performance of a contact textile-based light diffuser for photodynamic therapy.

    Science.gov (United States)

    Khan, Tania; Unternährer, Merthan; Buchholz, Julia; Kaser-Hotz, Barbara; Selm, Bärbel; Rothmaier, Markus; Walt, Heinrich

    2006-03-01

    Medical textiles offer a unique contact opportunity that could provide value-added comfort, reliability, and safety for light or laser-based applications. We investigated a luminous textile diffuser for use in photodynamic therapy. Textile diffusers are produced by an embroidery process. Plastic optical fibers are bent and sewn into textile to release light by macrobending. A reflective backing is incorporated to improve surface homogeneity, intensity, and safety. Clonogenic assay (MCF-7 cells) and trypan blue exclusion (NuTu19 cells) tests were performed in vitro using 0.1μg/ml m-THPC with three textile diffusers and a standard front lens diffuser. Heating effects were studied in solution and on human skin. PDT application in vivo was performed with the textile diffuser on equine sarcoids (three animals, 50mW/cm(2), 10-20J) and eight research animals. Lastly, computer simulations were performed to see how the textile diffuser might work on a curved object. At low fluency rate, there is a trend for the textile diffuser to have lower survival rates than the front lens diffuser for both cell lines. The textile diffuser was observed to retain more heat over a long period (>1min). All animals tolerated the treatments well and showed similar initial reactions. The simulations showed a likely focusing effect in a curved geometry. The initial feasibility and application using a textile-based optical diffuser has been demonstrated. Possibilities that provide additional practical advantages of the textile diffuser are discussed.

  10. Application of fluorescence spectroscopy and imaging in the detection of a photosensitizer in photodynamic therapy

    Science.gov (United States)

    Zang, Lixin; Zhao, Huimin; Zhang, Zhiguo; Cao, Wenwu

    2017-02-01

    Photodynamic therapy (PDT) is currently an advanced optical technology in medical applications. However, the application of PDT is limited by the detection of photosensitizers. This work focuses on the application of fluorescence spectroscopy and imaging in the detection of an effective photosenzitizer, hematoporphyrin monomethyl ether (HMME). Optical properties of HMME were measured and analyzed based on its absorption and fluorescence spectra. The production mechanism of its fluorescence emission was analyzed. The detection device for HMME based on fluorescence spectroscopy was designed. Ratiometric method was applied to eliminate the influence of intensity change of excitation sources, fluctuates of excitation sources and photo detectors, and background emissions. The detection limit of this device is 6 μg/L, and it was successfully applied to the diagnosis of the metabolism of HMME in the esophageal cancer cells. To overcome the limitation of the point measurement using fluorescence spectroscopy, a two-dimensional (2D) fluorescence imaging system was established. The algorithm of the 2D fluorescence imaging system is deduced according to the fluorescence ratiometric method using bandpass filters. The method of multiple pixel point addition (MPPA) was used to eliminate fluctuates of signals. Using the method of MPPA, SNR was improved by about 30 times. The detection limit of this imaging system is 1.9 μg/L. Our systems can be used in the detection of porphyrins to improve the PDT effect.

  11. Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients.

    Science.gov (United States)

    Zamarrón, Alicia; García, Marta; Río, Marcela Del; Larcher, Fernando; Juarranz, Ángeles

    2017-09-29

    PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role.

  12. Photodynamic therapy (PDT) to treat a chronic skin wound in a dog

    Science.gov (United States)

    Hage, Raduan; Plapler, Hélio; Bitar, Renata A.

    2008-02-01

    Photodynamic Therapy (PDT) is an emerging and promising therapeutic modality for treatment of a wide variety of malignant and nononcologic tumors, as well as in the treatment of infected skin ulcers. This study evaluated the effectiveness of the PDT to treat a chronic skin wound that had been already subjected to several clinical and surgical type treatments in a dog. The animal with an infected chronic skin wound with 8 cm diameter in the left leg received an injection of an aqueous solution of 1% methylene blue (MB) with 2% lidocaine into the lesion. After MB injection the wound was irradiated using a LED (LED-VET MMOptics(r)) with a wavelength between 600 and 700 nm, 2 cm diameter circular light beam, of 150 mW of power, light dose of 50 J/cm2. After 3 and 6 weeks PDT was repeated and the wound was re-evaluated. Complete healing was achieved 10 weeks after the first procedure.

  13. Clinical and Microbiological Effects of Photodynamic Therapy Associated with Non-surgical Treatment in Aggressive Periodontitis

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Chitsazi

    2014-09-01

    Full Text Available Background and aims. The aim of this study was to compare the effectiveness of adjunctive photodynamic therapy (PDT in the treatment of aggressive periodontitis. Materials and methods. A total of 24 patients with clinical diagnosis of aggressive periodontitis received scaling and root planing (SRP for periodontal treatment. In a split-mouth design study, the teeth of one quadrant of each arch with ≥4 mm of probing depth were selected randomly for additional treatment with PDT (test group. PDT was performed with a diode laser beam with a wavelength of 670-690 nm and a power of 75 Mw. The control group consisted of selected teeth of the contralateral quadrant (SRP only. Before any treatment, subgingival plaque samples were collected by an endodontic paper cone for microbiological analysis by real-time polymerase chain reaction (PCR for detection of Aggregatibacter actinomy-cetecommitans. Clinical parameters including clinical attachment loss (CAL as primary outcome, plaque index (PI, bleed-ing on probing (BOP, probing depth (PD and gingival recession (REC were measured at baseline and after 90 days. Inter-group and intra-group statistical analyses were performed. Results. Treatment groups showed an improvement in all the clinical parameters and a significant reduction in the counts of A. actinomycetecommitans at 90 days compared to baseline (P 0.05. Conclusion. Within the limitations of this study, the results did not show additional benefits from PDT as an adjunctive treatment for patients with aggressive periodontitis.

  14. Enhancement of the efficiency of photodynamic therapy by combination with the microtubule inhibitor vincristine

    Science.gov (United States)

    Ma, Li Wei; Berg, Kristian; Danielsen, Havard E.; Iani, Vladimir; Moan, Johan

    1996-01-01

    Combination effects of photodynamic therapy (PDT) with meso-tetra (di-adjacent- sulfonatophenyl) porphine (TPPS2a) and the microtubule (MT) inhibitor, vincristine (VCR), were studied in the CaD2 mouse tumor model in mice. A synergistic effect was found when VCR, at an almost nontoxic dose (1 mg/kg), was injected i.p. into the mice 6 hr before PDT. The data on mitotic index show a 4 - 5 fold accumulation of the cells in mitosis 6 hr after injection of VCR into the mice. Cell cycle and ploidy distributions in tumor tissues were determined by means of image analysis with measurement of integrated optical density after Feulgen reaction on monolayers. Ploidy distribution of the tumors was not significantly changed 6 and 12 hr after administration of VCR only, while an increasing aneuploidy was observed 24 and 48 hr after VCR treatment. No prominent changes of the cell cycle and ploidy distributions were found in the tumor tissues after PDT or PDT combined with VCR.

  15. B16F1 melanoma cells upregulate melanin synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    Moder, A.; Gassner, F.; Krammer, B.; Thalhamer, J.; Hammerl, P.

    2003-01-01

    Full text: The success of photodynamic therapy (PDT) of melanotic tumors is severely limited by insufficient penetration of light into deeper tissue layers. In this study, we analyzed the effect of PDT on the melanin production of the melanoma cell line B16F1. In vitro, these cells produce only little melanin. However, after PDT we found a dramatic elevation in intracellular melanin. Melanin production increased with, both, the concentration of the sensitizing agent and the light dose, and was found to continue for several hours after cell death. PDT-induced melanin synthesis was not prevented by the addition of cycloheximide or actinomycin D prior to irradiation, indicating that de-novo protein synthesis and transcriptional activity are not required for this effect. We also analyzed tyrosinase activity, a key enzyme in melanin biosynthesis, in PDT-treated B16 cells. Tyrosinase activity was found in PDT-treated as well as untreated cells. Cell fractionation experiments showed that tyrosinase was present in the cytosolic as well as the melanosomal fractions of, both, PDT-treated (melanin-high) as well as untreated (melanin-low) cells. These data indicate that PDT-induced production of melanin is not controlled at the transcriptional or translational level and that tyrosinase is not likely an essential regulator in this process. (author)

  16. Photodynamic therapy efficient using high power LED's to eliminate breast cancer cells

    International Nuclear Information System (INIS)

    Castillo Millan, J.; Gardunno Medina, J. A.; Ramon Gallegos, E.; De la Rosa, J.; Moreno Garcia, E.

    2009-01-01

    The photodynamic therapy (PDT) is a therapeutic modality that requires light, a photo sensitizer and oxygen. In poor countries, a problem for his application is the laser cost for irradiate, due to this, a light source was constructed with LED's that emit to 625 nm and his efficiency to eliminate breast cancer cells was measured. Two lines of breast cancer (MDA-MB-231 and MCF-7) and not cancerous cells (HaCat) were exposed to 40 and 80 μg/mL of ALA concentrations during 24h to induce the photo sensitizer PpIX, and were radiated to 120 and 240 J/cm 2 , 24 h later on the cellular death was measured by Alamar blue method. The PDT elimination efficiency, when were used the doses of light of 120 and 240 J/cm 2 , was 61 and 71 % for MDA, 46 and 49.2 % for MCF-7 and 87.2 and 94.1 % for HaCaT respectively. The constructed light source showed to be efficient in the elimination of the cancerous cells. (Author)

  17. Photodynamic Therapy for Cancer Cells Using a Flash Wave Light Xenon Lamp

    Science.gov (United States)

    Kimura, Makoto; Kashikura, Kasumi; Yokoi, Satomi; Koiwa, Yumiko; Tokuoka, Yoshikazu; Kawashima, Norimichi

    We determined photodynamic therapy (PDT) efficacy using a flash wave (FW) and a continuous wave (CW) light, of which the fluence rate was 70 W/cm2, for murine thymic lymphoma cells (EL-4) cultivated in vitro. The irradiation frequency and the pulse width of the FW light were in the range of 1-32 Hz and less than one millisecond, respectively. 5-Aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) was used as a photosensitizer. When EL-4 with ALA administration was irradiated by the light for 4 h (irradiation fluence: 1.0J/cm2), the survival rate of EL-4 by the FW light was lower than that by the CW light, except for the FW light with irradiation frequency of 32 Hz, and decreased gradually with decreasing irradiation frequency. Moreover, the FW light, especially at lower irradiation frequency, was superior to the CW light for the generation of singlet oxygen in an aqueous PpIX solution. Therefore, thehigher PDT efficacy for EL-4 of the FW light would be caused by the greater generation of singlet oxygen in the cells.

  18. In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

    2009-05-02

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

  19. Weighted optimization of irradiance for photodynamic therapy of port wine stains

    Science.gov (United States)

    He, Linhuan; Zhou, Ya; Hu, Xiaoming

    2016-10-01

    Planning of irradiance distribution (PID) is one of the foremost factors for on-demand treatment of port wine stains (PWS) with photodynamic therapy (PDT). A weighted optimization method for PID was proposed according to the grading of PWS with a three dimensional digital illumination instrument. Firstly, the point clouds of lesions were filtered to remove the error or redundant points, the triangulation was carried out and the lesion was divided into small triangular patches. Secondly, the parameters such as area, normal vector and orthocenter for optimization of each triangular patch were calculated, and the weighted coefficients were determined by the erythema indexes and areas of patches. Then, the optimization initial point was calculated based on the normal vectors and orthocenters to optimize the light direction. In the end, the irradiation can be optimized according to cosine values of irradiance angles and weighted coefficients. Comparing the irradiance distribution before and after optimization, the proposed weighted optimization method can make the irradiance distribution match better with the characteristics of lesions, and has the potential to improve the therapeutic efficacy.

  20. Photodynamic therapy for early malignancies in the lower female genital tract

    Science.gov (United States)

    Lobraico, Rocco V.

    1990-09-01

    A total of 14 patients who had failed all conventional modalities for cancer of the vulva vagina and perianal area were treated with photodynamic therapy PDT. The affinity of porphyrins to neopJ. astic tissue enables treatment to be concentrated at the tumor site. An Aurora FL Argon pumped dye laser (Cooper LaserSonics Inc. USA) was used to pump dicyanomethylene dye as an activating source for a red light at a wavelength of 630 nm. The combination of a tumor localizing photosensitizer and photoactivating red light produces a photo chemical reaction that is destructive to the cancerous lesion. The treatment time varied between 10-30 minutes. Vulvar sites ranged from 9-38 cm2. Delivered light doses were from 50-125 J/cm2 and power density from 50 to 75 mW/cm2. A complete response was obtained in 80 of the sites treated as evidenced by negative biopsies taken at 3 months post treatment. Adverse reactions to PDT included a transient cutaneous photosensitivity due to retention of the photosensitizers in the skin. This reaction usually persisted from 45-60 days. 1.

  1. Photodynamic therapy using upconversion nanoparticles prepared by laser ablation in liquid

    Energy Technology Data Exchange (ETDEWEB)

    Ikehata, Tomohiro; Onodera, Yuji; Nunokawa, Takashi [Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Hirano, Tomohisa; Ogura, Shun-ichiro; Kamachi, Toshiaki [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Odawara, Osamu [Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Wada, Hiroyuki, E-mail: wada.h.ac@m.titech.ac.jp [Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan)

    2015-09-01

    Highlights: • Highly crystalline upconversion nanoparticles were prepared by laser ablation in liquid. • Highly transparent near-IR irradiation generated singlet oxygen. • Viability of cancer cells was significantly decreased by near-IR irradiation. - Abstract: Upconversion nanoparticles were prepared by laser ablation in liquid, and the potential use of the nanoparticles for cancer treatment was investigated. A Nd:YAG/SHG laser (532 nm, 13 ns, 10 Hz) was used for ablation, and the cancer treatment studied was photodynamic therapy (PDT). Morphology and crystallinity of prepared nanoparticles were examined by transmission electron microscopy and X-ray diffraction. Red and green emissions resulting from near-infrared excitation were observed by a fluorescence spectrophotometer. Generation of singlet oxygen was confirmed by a photochemical method using 1,3-diphenylisobenzofuran (DPBF). In vitro experiments using cultivated cancer cells were conducted to investigate PDT effects. Uptake of the photosensitizer by cancer cells and cytotoxicities of cancer cells were also examined. We conclude that the combination of PDT and highly crystalline nanoparticles, which were prepared by laser ablation in liquid, is an effective cancer treatment.

  2. Photoprotective Effect of the Plant Collaea argentina against Adverse Effects Induced by Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Leandro Mamone

    2014-01-01

    Full Text Available Photodynamic therapy (PDT is a treatment modality for tumours and other accessible lesions based on the combination of light and a photosensitizer (PS accumulated in the target tissue. The main disadvantage of PDT is PS retention after treatment during long time periods that conduces to cutaneous damage. It is believed that singlet oxygen is responsible for that skin photosensitization. The aim of this work was to evaluate the photoprotective activity of the methanolic extract of the Argentinian plant Collaea argentina against PDT under several treatments and employing different PSs. C. argentina exhibited photoprotective activity against aminolevulinic acid- (ALA- PDT in the LM2 murine adenocarcinoma cell line. The photoprotection was dependant on the extract concentration and the incubation time, being detectable from 40 μg/mL onwards and at least after 3 h exposure of the cells. C. argentina extract protects these mammalian tumor cells against PDT effects, and it interferes with the oxygen singlet production from PSs during PDT treatment. We propose that it will be a promising agent to protect cells against PDT-induced skin sensitivity.

  3. Assessment of Rose Bengal vs. Riboflavin Photodynamic Therapy for Inhibition of Fungal Keratitis Isolates

    Science.gov (United States)

    Arboleda, Alejandro; Miller, Darlene; Cabot, Florence; Taneja, Mukesh; Aguilar, Mariela C.; Alawa, Karam; Amescua, Guillermo; Yoo, Sonia H.; Parel, Jean-Marie

    2014-01-01

    Purpose To compare the in vitro effect of rose bengal and riboflavin as photosensitizing agents for photodynamic therapy (PDT) on fungal isolates that are common causes of fungal keratitis Design Experimental study Methods Three isolates (Fusarium solani, Aspergillus fumigatus, Candida albicans) recovered from patients with confirmed fungal keratitis were used in the experiments. Isolates were grown on Sabouraud-Dextrose agar, swabbed and prepared in suspension, and one milliliter aliquots were inoculated onto test plates in triplicate. Test plates were separated into 5 groups: Group 1 - no treatment, Group 2 - 0.1% rose bengal alone, Group 3 - 518 nm irradiation alone, Group 4 - riboflavin PDT (riboflavin + 375 nm irradiation), and Group 5 - rose bengal PDT (rose bengal + 518 nm irradiation). Irradiation was performed over a circular area using either a green LED array (peak wavelength: 518 nm) or a UV-A LED array (peak wavelength: 375 nm). Test plates were irradiated with an energy density of 5.4 J/cm2. Later, plates were placed in a 30° C incubator and observed for growth. Results Rose bengal-mediated PDT successfully inhibited the growth of all three fungal isolates in the irradiated area. All other groups exhibited unrestricted growth throughout the plate. Conclusions Rose bengal-mediated PDT successfully inhibited the growth of three types of fungi. No other experimental groups, including riboflavin-mediated PDT, had any inhibitory effect on the isolates. The results might be useful for the treatment of patients suffering from corneal infection. PMID:24792103

  4. The role of cytoskeleton and adhesion proteins in the resistance to photodynamic therapy. Possible therapeutic interventions.

    Science.gov (United States)

    Di Venosa, Gabriela; Perotti, Christian; Batlle, Alcira; Casas, Adriana

    2015-08-01

    It is known that Photodynamic Therapy (PDT) induces changes in the cytoskeleton, the cell shape, and the adhesion properties of tumour cells. In addition, these targets have also been demonstrated to be involved in the development of PDT resistance. The reversal of PDT resistance by manipulating the cell adhesion process to substrata has been out of reach. Even though the existence of cell adhesion-mediated PDT resistance has not been reported so far, it cannot be ruled out. In addition to its impact on the apoptotic response to photodamage, the cytoskeleton alterations are thought to be associated with the processes of metastasis and invasion after PDT. In this review, we will address the impact of photodamage on the microfilament and microtubule cytoskeleton components and its regulators on PDT-treated cells as well as on cell adhesion. We will also summarise the impact of PDT on the surviving and resistant cells and their metastatic potential. Possible strategies aimed at taking advantage of the changes induced by PDT on actin, tubulin and cell adhesion proteins by targeting these molecules will also be discussed.

  5. A Medical Manipulator System with Lasers in Photodynamic Therapy of Port Wine Stains

    Directory of Open Access Journals (Sweden)

    Xingtao Wang

    2014-01-01

    Full Text Available Port wine stains (PWS are a congenital malformation and dilation of the superficial dermal capillary. Photodynamic therapy (PDT with lasers is an effective treatment of PWS with good results. However, because the laser density is uneven and nonuniform, the treatment is carried out manually by a doctor thus providing little accuracy. Additionally, since the treatment of a single lesion can take between 30 and 60 minutes, the doctor can become fatigued after only a few applications. To assist the medical staff with this treatment method, a medical manipulator system (MMS was built to operate the lasers. The manipulator holds the laser fiber and, using a combination of active and passive joints, the fiber can be operated automatically. In addition to the control input from the doctor over a human-computer interface, information from a binocular vision system is used to guide and supervise the operation. Clinical results are compared in nonparametric values between treatments with and without the use of the MMS. The MMS, which can significantly reduce the workload of doctors and improve the uniformity of laser irradiation, was safely and helpfully applied in PDT treatment of PWS with good therapeutic results.

  6. Synthesis and biological evaluation of porphyrin-polyamine conjugates as potential agents in photodynamic therapy

    International Nuclear Information System (INIS)

    Lamarche, Francois

    2004-01-01

    The synthesis of photosensitizers that specifically recognize tumoral cells constitutes a challenging step in the field of photodynamic therapy. To this end, we designed a new class of porphyrins linked to natural polyamines (spermidine, spermine). As a first step, we synthesized para and ortho-carboxy-propyl-oxy-phenyl-tritolyl-porphyrins bearing spermidine or spermine. Then, we designed two precursors, N4-aminobutyl-spermidine-Boc2 and N4-aminobutyl-spermine-Boc3. These derivatives have been fixed on carboxy-porphyrins, protoporphyrin IX and chlorin e6. These new compounds have been characterized by MALDI spectrometry, UV-Visible and 1 H NMR spectroscopy. They have been found to produce singlet oxygen. Biological activity study of these photosensitizers has been realized on K562 cell line, irradiated with fluorescent bulbs. In vitro tests of these porphyrins have shown their photo-cytotoxic activity and protoporphyrins-polyamines have been able to trigger early apoptotic events. Finally, preliminary results obtained with chlorin e6-polyamines, irradiated with red light, seem to show that these structures are good candidates for an application in PDT. (author) [fr

  7. Nanoparticle-based photodynamic therapy on non-melanoma skin cancer

    Science.gov (United States)

    Fanjul-Vélez, F.; Arce-Diego, J. L.

    2018-02-01

    There are several advantages of Photodynamic Therapy (PDT) for nonmelanoma skin cancer treatment compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages its noninvasive nature, the use of non ionizing radiation and its high selectivity can be mentioned. Despite all these advantages, the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. An adequate dosimetry is needed in order to personalize the protocol. There are strategies that try to overcome the current PDT shortcomings, such as the improvement of the photosensitizer accumulation in the target tissue, optical radiation distribution optimization or photochemical reactions maximization. These strategies can be further complemented by the use of nanostructures with conventional PDT. Customized dosimetry for nanoparticle-based PDT requires models in order to adjust parameters of different nature to get an optimal tumor removal. In this work, a predictive model of nanoparticle-based PDT is proposed and analyzed. Dosimetry in nanoparticle-based PDT is going to be influenced by photosensitizer-nanoparticle distribution in the malignant tissue, its influence in the optical radiation distribution and the subsequent photochemical reactions. Nanoparticles are considered as photosensitizer carriers on several types of non-melanoma skin cancer. Shielding effects are taken into account. The results allow to compare the estimated treatment outcome with and without nanoparticles.

  8. Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

    Science.gov (United States)

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

  9. Hypericin-photodynamic therapy (PDT) using an alternative treatment regime suitable for multi-fraction PDT.

    Science.gov (United States)

    Thong, Patricia Soo-Ping; Watt, Frank; Ren, Min Qin; Tan, Puay Hoon; Soo, Khee Chee; Olivo, Malini

    2006-01-02

    Photodynamic therapy (PDT) outcome depends on the conditions under which it is carried out. Maintaining the tumour tissue oxygen level is important for PDT efficacy and using a low fluence rate can improve outcome. In this work we studied the response of human nasopharyngeal carcinoma tumours in murine models to hypericin-PDT carried out under low fluence and fluence rate. A drug-light interval (DLI) of 1h or 6h was used for 1h-PDT and 6h-PDT, respectively. Evan's blue test was used to assess necrosis and TUNEL staining for apoptosis. Nuclear microscopy was used to quantify elemental concentrations in tumours. Serum vascular endothelial growth factor (VEGF) levels were also determined. TUNEL results showed that 6h-PDT induced significantly more apoptosis compared to 1h-PDT (ptreatment regime is suitable for the alternative approach of multi-fraction PDT in which the tumour can be exposed to multiple PDT fractions for complete tumour response. This alternative approach might yield improved outcome.

  10. Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

    Science.gov (United States)

    Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

    2015-05-01

    There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

  11. Imidazole and beta-carotene photoprotection against photodynamic therapy evaluated by synchrotron infrared microscopy

    Science.gov (United States)

    Bosio, Gabriela N.; Parisi, Julieta; García Einschlag, Fernando S.; Mártire, Daniel O.

    2018-04-01

    In order to better understand the role of β-carotene and imidazole on the Photodynamic Therapy (PDT) mechanism, synchrotron infrared microscopy was used to detect the associated intracellular biochemical modifications following the visible light irradiation of HeLa cells incubated with these compounds as typical hydrophobic and hydrophilic singlet oxygen quenchers, respectively. For this purpose, PDT was performed employing the hydrophilic sensitizer 5,10,15,20-Tetrakis (1-methyl-4-pyridinio) porphyrin tetra (p-toluenesulfonate), TMPyP, and the hydrophobic sensitizer 5-(4-Methoxycarboxyphenyl)-10,15,20-triphenyl-21H,23H-porphyrin. The single cell IR spectra of PDT-treated, PDT plus quencher-treated and control HeLa cells were recorded at the SOLEIL Synchrotron Infrared SMIS beamline targeting specifically the cell nucleus. Principal Component Analysis (PCA) was used to assess the IR spectral changes. PCA revealed that there is a frequency shift of the protein Amide I vibrational band for the assays with the TMPyP sensitizer, indicating changes in the protein secondary structures of the PDT-treated cancer cells compared to the controls. In addition, the scores in those cells treated with both quenchers appear to be similar to the controls indicating a photoprotective effect. Comparative experiments carried out with SKMEL-28 and HaCat cells showed non- significant photoprotective effects of β-carotene and imidazole.

  12. Thermal distribution in biological tissue at laser induced fluorescence and photodynamic therapy

    Science.gov (United States)

    Krasnikov, I. V.; Seteikin, A. Yu.; Drakaki, E.; Makropoulou, M.

    2012-03-01

    Laser induced fluorescence spectroscopy and photodynamic therapy (PDT) are techniques currently introduced in clinical applications for visualization and local destruction of malignant tumours as well as premalignant lesions. During the laser irradiation of tissues for the diagnostic and therapeutic purposes, the absorbed optical energy generates heat, although the power density of the treatment light for surface illumination is normally low enough not to cause any significantly increased tissue temperature. In this work we tried to evaluate the utility of Monte Carlo modeling for simulating the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed UV laser and a continuous wave visible laser beam. The analysis of the results showed that heat is not localized on the surface, but it is collected inside the tissue. By varying the boundary conditions on the surface and the type of the laser radiation (continuous or pulsed) we can reach higher than normal temperature inside the tissue without simultaneous formation of thermally damaged tissue (e.g. coagulation or necrosis zone).

  13. Results and survival after photodynamic therapy in early-stage esophageal carcinoma

    Science.gov (United States)

    Spinelli, Pasquale; Mancini, Andrea; dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

    1996-01-01

    From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

  14. Clinical trials of a new chlorin photosensitizer for photodynamic therapy of malignant tumors

    Science.gov (United States)

    Privalov, Valeriy A.; Lappa, Alexander V.; Seliverstov, Oleg V.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.; Kochneva, Elena V.; Evnevich, Michail V.; Anikina, Alla S.; Reshetnicov, Andrey V.; Zalevsky, Igor D.; Kemov, Yuriy V.

    2002-06-01

    Photodynamic therapy (PDT) was performed with a new photosensitizer, a water soluble form of chlorins (Radachlorin, Russia) possessing an absorption peak around 662 nm. As light source there was used the diode laser (ML-662-SP, Russia) with 662 nm wavelength and 2.5 W optical power. The sensitizer had passed broad pre-clinical in vitro and in vivo studies, which showed safety and efficiency of it. PDT was applied to 51 patients with basal cell cancer of the skin (about 60% of all cases), breast cancer, lip cancer, melanoma, cancer of esophagus, stomach, and rectum, cancer and leucoplacia of vulva, malignant ganglioneuroma, sarcoma of soft tissue, cancer and reticular sarcoma of thyroid gland, cancer of ductus choledochus. Most of non-basalioma patients had either forth stage or recurrence of disease. The sensitizer was injected intravenously or applied externally (Radachlorin gel). There were used surface, endoscopic, and interstitial ways of irradiation. Full tumor regression with excellent cosmetic effect was reached in 100% cases of 1-3 stage basal cell cancer patients treated with intravenous Radachlorin injection. In most other (non-basalioma) cases significant regression of tumors and improvement of life quality of patients (recanalization and regain of conductivity) was obtained.

  15. Identification and ultrastructural imaging of photodynamic therapy-induced microfilaments by atomic force microscopy

    International Nuclear Information System (INIS)

    Jung, Se-Hui; Park, Jin-Young; Yoo, Je-Ok; Shin, Incheol; Kim, Young-Myeong; Ha, Kwon-Soo

    2009-01-01

    Atomic force microscopy (AFM) is an emerging technique for imaging biological samples at subnanometer resolution; however, the method is not widely used for cell imaging because it is limited to analysis of surface topology. In this study, we demonstrate identification and ultrastructural imaging of microfilaments using new approaches based on AFM. Photodynamic therapy (PDT) with a new chlorin-based photosensitizer DH-II-24 induced cell shrinkage, membrane blebbing, and reorganization of cytoskeletons in bladder cancer J82 cells. We investigated cytoskeletal changes using confocal microscopy and atomic force microscopy. Extracellular filaments formed by PDT were analyzed with a tandem imaging approach based on confocal microscopy and atomic force microscopy. Ultrathin filaments that were not visible by confocal microscopy were identified as microfilaments by on-stage labeling/imaging using atomic force microscopy. Furthermore, ultrastructural imaging revealed that these microfilaments had a stranded helical structure. Thus, these new approaches were useful for ultrastructural imaging of microfilaments at the molecular level, and, moreover, they may help to overcome the current limitations of fluorescence-based microscopy and atomic force microscopy in cell imaging.

  16. Blood vessel damage correlated with irradiance for in vivo vascular targeted photodynamic therapy

    Science.gov (United States)

    Zhang, Jinde; Tan, Zou; Niu, Xiangyu; Lin, Linsheng; Lin, Huiyun; Li, Buhong

    2016-10-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely utilized for the prevention or treatment of vascular-related diseases, including age-related macular degeneration, port-wine stains and prostate cancer. In order to quantitative assessment the blood vessel damage during V-PDT, nude mice were implanted with Titanium dorsal skin window chambers for in vivo V-PDT studies. For treatments, various irradiances including 50, 75, 100 and 200 mW/cm2 provided by a 532 nm semiconductor laser were performed with the same total light dose of 30 J/cm2 after the mice were intravenously injection of Rose Bengal for 25 mg/Kg body weight. Laser speckle imaging and microscope were used to monitor blood flow dynamics and vessel constriction during and after V-PDT, respectively. The V-PDT induced vessel damages between different groups were compared. The results show that significant difference in blood vessel damage was found between the lower irradiances (50, 75 and 100 mW/cm2) and higher irradiance (200 mW/cm2), and the blood vessel damage induced by V-PDT is positively correlated with irradiance. This study implies that the optimization of irradiance is required for enhancing V-PDT therapeutic efficiency.

  17. Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model

    Science.gov (United States)

    Swartling, Johannes; Höglund, Odd V.; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

    2016-02-01

    Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

  18. Photodynamic therapy in the cattle protozoan Tritrichomonas foetus cultivated on superhydrophilic carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    Machado, Susane Moreira [Laboratory of Tissue and Cell Biology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Pacheco-Soares, Cristina [Laboratory of Tissue and Cell Biology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Laboratory of Dynamics of Cellular Compartments, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Marciano, Fernanda Roberta; Lobo, Anderson Oliveira [Laboratory of Biomedical Nanotechnology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Soares da Silva, Newton, E-mail: nsoares@univap.br [Laboratory of Tissue and Cell Biology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Laboratory of Dynamics of Cellular Compartments, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil)

    2014-03-01

    Superhydrophilic vertically aligned carbon nanotubes (VACNT-O{sub 2}) were used for the first time as scaffolds for photodynamic therapy (PDT) to induce inhibition of cell division in eukaryotic cells. VACNT-O{sub 2} scaffolds were produced on Ti substrates using plasma enhanced chemical vapor deposition technique and functionalized by oxygen plasma. Scanning electron microscopy (SEM) analysis was performed to characterize the surface changes of the protozoan and interaction with VACNT-O{sub 2}. Characterization of lipid and total protein expression was performed with protozoa that were or not treated with PDT. Quantification of protein was conducted using Qubit fluorometer and separated on a polyacrylamide gel. SEM analysis showed the release of lipid vesicles by protozoa after the PDT. These vesicles were characterized by the PKH26 fluorescent probe. The results demonstrated a greater amount of protein released after PDT than in the control. When analyzing the protein material in polyacrylamide gel, a significant protein expression of approximately 65 kDa was found. A model identified the programmed death of Tritrichomonas foetus after the PDT was also proposed. - Highlights: • VAMWCNT-O{sub 2} used for the first time as scaffolds for study in parasitic protozoan. • VAMWCNT-O{sub 2} films applied to understand spreading mechanisms of parasitic protozoan. • A release of a protein of approximately 65kDa of protozoan was also observed.

  19. Photodynamic therapy in the cattle protozoan Tritrichomonas foetus cultivated on superhydrophilic carbon nanotube

    International Nuclear Information System (INIS)

    Machado, Susane Moreira; Pacheco-Soares, Cristina; Marciano, Fernanda Roberta; Lobo, Anderson Oliveira; Soares da Silva, Newton

    2014-01-01

    Superhydrophilic vertically aligned carbon nanotubes (VACNT-O 2 ) were used for the first time as scaffolds for photodynamic therapy (PDT) to induce inhibition of cell division in eukaryotic cells. VACNT-O 2 scaffolds were produced on Ti substrates using plasma enhanced chemical vapor deposition technique and functionalized by oxygen plasma. Scanning electron microscopy (SEM) analysis was performed to characterize the surface changes of the protozoan and interaction with VACNT-O 2 . Characterization of lipid and total protein expression was performed with protozoa that were or not treated with PDT. Quantification of protein was conducted using Qubit fluorometer and separated on a polyacrylamide gel. SEM analysis showed the release of lipid vesicles by protozoa after the PDT. These vesicles were characterized by the PKH26 fluorescent probe. The results demonstrated a greater amount of protein released after PDT than in the control. When analyzing the protein material in polyacrylamide gel, a significant protein expression of approximately 65 kDa was found. A model identified the programmed death of Tritrichomonas foetus after the PDT was also proposed. - Highlights: • VAMWCNT-O 2 used for the first time as scaffolds for study in parasitic protozoan. • VAMWCNT-O 2 films applied to understand spreading mechanisms of parasitic protozoan. • A release of a protein of approximately 65kDa of protozoan was also observed

  20. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    International Nuclear Information System (INIS)

    Paula, Leonardo B. de; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.

    2015-01-01

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×10 13 or 1.50×10 13 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×10 13 or 1.50×10 13 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments. - Highlights: • Current protocols in nanotechnology allow for biocompatible magnetic nanoparticles being associated with photosensitizer photoactive drugs, which could lead to perfectly controlled drug release. • The combination of the HPT and PDT therapies can be useful to develop further protocols for both advanced in vitro and in vivo assays. • Magnetic nanodevices associated with therapies have led to the decreased of proliferation of cell population that provides a favorable environment for tumor progression

  1. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    Energy Technology Data Exchange (ETDEWEB)

    Paula, Leonardo B. de [Departamento de Química, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14049-900 (Brazil); Primo, Fernando L. [Departamento de Química, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Nanophoton Company, SUPERA Innovation and Technology Park, Av. Doutora Nadir de Aguiar, 1805, Universidade de São Paulo, Ribeirão Preto, P 14056-680 (Brazil); Pinto, Marcelo R. [Departamento de Química, Laboratório de Enzimologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Morais, Paulo C. [Instituto de Física, Universidade de Brasília, Brasília, DF 70910-900 (Brazil); School of Automation, Huazhong University of Science and Technology, Wuhan 430074 (China); and others

    2015-04-15

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×10{sup 13} or 1.50×10{sup 13} particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×10{sup 13} or 1.50×10{sup 13} magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments. - Highlights: • Current protocols in nanotechnology allow for biocompatible magnetic nanoparticles being associated with photosensitizer photoactive drugs, which could lead to perfectly controlled drug release. • The combination of the HPT and PDT therapies can be useful to develop further protocols for both advanced in vitro and in vivo assays. • Magnetic nanodevices associated with therapies have led to the decreased of proliferation of cell population that provides a favorable environment for tumor progression.

  2. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    Directory of Open Access Journals (Sweden)

    Malini Olivo

    2010-05-01

    Full Text Available Photodynamic therapy (PDT has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS, which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS, that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  3. Device for fluorescent control and photodynamic therapy of age-related macula degeneration

    Science.gov (United States)

    Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

    2004-07-01

    Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

  4. In vivo 808 nm image-guided photodynamic therapy based on an upconversion theranostic nanoplatform

    Science.gov (United States)

    Liu, Xiaomin; Que, Ivo; Kong, Xianggui; Zhang, Youlin; Tu, Langping; Chang, Yulei; Wang, Tong Tong; Chan, Alan; Löwik, Clemens W. G. M.; Zhang, Hong

    2015-09-01

    A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, 1O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm-2) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy.A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii

  5. Chemical luminescence measurement of singlet oxygen generated by photodynamic therapy in solutions in real time

    Science.gov (United States)

    Luo, Shiming; Xing, Da; Zhou, Jing; Qin, Yanfang; Chen, Qun

    2005-04-01

    Photodynamic therapy (PDT) is a cancer therapy that utilizes optical energy to activate a photosensitizer drug in a target tissue. Reactive oxygen species (ROS), such as 1O2 and superoxide, are believed to be the major cytotoxic agents involved in PDT. Although current PDT dosimetry mostly involves measurements of light and photosensitizer doses delivered to a patient, the quantification of ROS production during a treatment would be the ultimate dosimetry of PDT. Technically, it is very difficult and expensive to directly measure the fluorescence from 1O2, due to its extreme short lifetime and weak signal strength. In this paper, Photofrin(R) and 635nm laser were used to generate 1O2 and superoxide in a PDT in solution. Compound 3,7- dihydro-6-{4-[2-(N"-(5-fluoresceinyl) thioureido) ethoxy] phenyl}-2- methylimidazo{1,2-a} pyrazin-3-one sodium salt,an Cyp- ridina luciferin analog commonly referred as FCLA, was used as a chemical reporter of ROS. The 532nm chemiluminescence (CL) from the reaction of the FCLA and ROS was detected with a photon multiplier tube (PMT) system operating at single photon counting mode. With the setup, we have made detections of ROS generated by PDT in real time. By varying the amount of conventional PDT dosage (photosensitizer concentration, light irradiation fluence and its delivery rate) and the amount of FCLA, the intensity of CL and its consumption rate were investigated. The results show that the intensity and temporal profile of CL are highly related to the PDT treatment parameters. This suggests that FCLA CL may provide a highly potential alternative for ROS detection during PDT.

  6. Circumvention of resistance to photodynamic therapy in doxorubicin-resistant sarcoma by photochemical internalization of gelonin.

    Science.gov (United States)

    Olsen, Cathrine Elisabeth; Berg, Kristian; Selbo, Pål Kristian; Weyergang, Anette

    2013-12-01

    A wide range of anti-cancer therapies have been shown to induce resistance upon repetitive treatment and such adapted resistance may also cause cross-resistance to other treatment modalities. We here show that MES-SA/Dx5 cells with adapted resistance to doxorubicin (DOX) are cross-resistant to photodynamic therapy (PDT). A DOX-induced increased expression of the reactive oxygen species (ROS)-scavenging proteins glutathione peroxidase (GPx) 1 and GPx4 in MES-SA/Dx5 cells was indicated as the mechanism of resistance to PDT in line with the reduction in PDT-generated ROS observed in this cell line. ROS-induced p38 activation was, in addition, shown to be reduced to one-third of the signal of the parental MES-SA cells 2h after PDT, and addition of the p38 inhibitor SB203580 confirmed p38 activation as a death signal after PDT in the MES-SA cells. The MES-SA/Dx5 cells were also cross-resistant to ionizing radiation in agreement with the increased GPx1 and GPx4 expression. Surprisingly, PDT-induced endo/lysosomal release of the ribosome-inactivating protein gelonin (photochemical internalization (PCI)) was more effective in the PDT-resistant MES-SA/Dx5 cells, as measured by synergy calculations in both cell lines. Analysis of death-inducing signaling indicated a low activation of caspase-3 and a strong PARP I cleavage after PDT and PCI in both cell lines. The PARP I activation was, however, stronger after PCI than after PDT in the MES-SA cells, but not in the MES-SA/Dx5 cells, and therefore cannot explain the strong PCI effect in the MES-SA/Dx5 cells. In conclusion PCI of recombinant gelonin circumvents ROS resistance in an apoptosis-independent manner. © 2013 Elsevier Inc. All rights reserved.

  7. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.

    Science.gov (United States)

    Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K; van Wijk, Albert C; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C; van Gulik, Thomas M; Storm, Gert; Heger, Michal

    2016-01-19

    Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.

  8. The exploitation of inflammation in photodynamic therapy of pleural cancer (Conference Presentation)

    Science.gov (United States)

    Davis, Richard W.; Miller, Joann; Houser, Cassandra L.; Klampatsa, Astero; Jenkins, Tim; Cengel, Keith A.; Albelda, Steven M.; Busch, Theresa M.

    2017-02-01

    The onset of inflammation is a well-known physiology in tumors treated with photodynamic therapy (PDT). After PDT, the release of danger signals causes an influx of neutrophils, activation of dendritic cells, and an eventual initiation of the adaptive immune response. However, inflammation also lies at a crucial fulcrum for treatment outcome, as it can stimulate the expression of resistance factors. Therefore, effective treatment with PDT requires an understanding of the holistic contribution of inflammation. Within, we outline two means of studying tumor inflammation in the setting of PDT. Experiments are conducted in murine models of mesothelioma, including those that incorporate surgery prior to PDT or pleural propagation of the disease. First, we use a chemiluminescent agent, luminol, to detect the influx of neutrophils by in vivo molecular imaging. This longitudinal approach allows for the repeated non-invasive monitoring of PDT-induced neutrophil influx. Data clearly identify protocol-specific differences in tumor-associated neutrophil activity. Second, we describe the application of cone-beam CT to detect the fibrosis associated with murine orthotropic mesothelioma models. This approach incorporates novel methods in image segmentation to accurately identify diffuse disease in the thoracic cavity. These studies lay the foundation for future research to correlate long-term response with local PDT-induced inflammation. Such methods in monitoring of inflammation or tumor burden will enable characterization of the consequences of combinatorial therapy (e.g., intraoperative PDT). Resulting data will guide the selection of pharmacological agents or molecular imaging techniques that respectively exploit inflammation for therapeutic or monitoring purposes.

  9. In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

    Science.gov (United States)

    Liu, Y H; Hawk, R M; Ramaprasad, S

    1995-01-01

    RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

  10. Comparison between scaling-root-planing (SRP and SRP/photodynamic therapy: six-month study

    Directory of Open Access Journals (Sweden)

    Berakdar Mohammad

    2012-04-01

    Full Text Available Abstract Introduction The purpose of this long-term clinical study was to examine the additional efficacy of photodynamic therapy (PDT to scaling and root planing (SRP in patients with chronic periodontal disease. Methods A total of 22 patients (mean age: 59.3 ± 11.7 years with chronic periodontal disease and four teeth with probing depth ≥ 5 mm were enrolled in the study. Inclusion criteria were: no systemic disease, no smoking, no pregnancy and no long-term medication. Beside the anamnesis, the following clinical parameters were assessed at baseline (one week before therapy, and one, three and six months after the therapy: bleeding on probing (BOP, plaque index (PI probing depth (PD, and clinical attachment loss. All measurements were done by the same examiner with a fixed periodontal probe (PCP 12, Hu-Friedy at six measurements/tooth. In each patient, two teeth were treated with SRP alone and two teeth with SRP and PDT (Periowave, Ondine Biopharma, Vancouver, Canada. The nonparametric Wilcoxon test for paired samples was used for comparison of the effect of the two treatments (p ≤ 0.05. Results After both types of treatment, the number of teeth positive for BOP declined. At baseline, the CAL measured 7.2 ± 1.2 mm (SRP or 8.1 ± 1.3 mm (SRP/PDT; one, three and six months after both types of treatment an improvement was observed. At baseline, the probing depth was 5.9 ± 0.8 mm (SRP or 6.4 ± 0.8 mm (SRP/PDT; after six months, an improvement of 2.4 ± 0.6 mm (SRP or 2.9 ± 0.8 mm (SRP/PDT was found. The greater reduction of the PD, achieved by a combination of SRP/PDT, was statistically significant after six months (p = 0.007. Conclusion This clinical study demonstrates that SRP in combination with PDT seems to be effective and is therefore suitable as an adjuvant therapy to the mechanical conditioning of the periodontal pockets in patients with chronic periodontal diseases.

  11. Quantitative Multi-Parametric Magnetic Resonance Imaging of Tumor Response to Photodynamic Therapy.

    Directory of Open Access Journals (Sweden)

    Tom J L Schreurs

    Full Text Available The aim of this study was to characterize response to photodynamic therapy (PDT in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome.CT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of BALB/c mice. Therapy consisted of intravenous injection of the photosensitizer Bremachlorin, followed by 10 min laser illumination (200 mW/cm2 of the tumor 6 h post injection. MRI at 7 T was performed at baseline, directly after PDT, as well as at 24 h, and 72 h. Tumor relaxation time constants (T1 and T2 and apparent diffusion coefficient (ADC were quantified at each time point. Additionally, Gd-DOTA dynamic contrast-enhanced (DCE MRI was performed to estimate transfer constants (Ktrans and volume fractions of the extravascular extracellular space (ve using standard Tofts-Kermode tracer kinetic modeling. At the end of the experiment, tumor viability was characterized by histology using NADH-diaphorase staining.The therapy induced extensive cell death in the tumor and resulted in significant reduction in tumor growth, as compared to untreated controls. Tumor T1 and T2 relaxation times remained unchanged up to 24 h, but decreased at 72 h after treatment. Tumor ADC values significantly increased at 24 h and 72 h. DCE-MRI derived tracer kinetic parameters displayed an early response to the treatment. Directly after PDT complete vascular shutdown was observed in large parts of the tumors and reduced uptake (decreased Ktrans in remaining tumor tissue. At 24 h, contrast uptake in most tumors was essentially absent. Out of 5 animals that were monitored for 2 weeks after treatment, 3 had tumor recurrence, in locations that showed strong contrast uptake at 72 h.DCE-MRI is an effective tool for visualization of vascular effects directly after PDT. Endogenous contrast parameters T1, T2, and ADC, measured at 24 to 72 h after PDT, are

  12. Antimicrobial Irrigants in the Endodontic Therapy

    OpenAIRE

    Iqbal, Azhar

    2012-01-01

    This paper highlights the importance of root canal disinfection. It discusses the different endodontic irrigants available and comments on how these can be used most effectively. Eliminating bacteria from the root canal system is an essential stage in endodontic therapy. An objective of endodontic treatment is removal of diseased tissue, elimination of bacteria from the canal system and prevention of recontamination. (1) Disinfection of the root canal system, as part of endodontic therapy, by...

  13. Comparative study of the effects of photodynamic therapy and conventional therapy on ligature induced peri-implantitis in dogs

    International Nuclear Information System (INIS)

    Hayek, Ricardo Rada Ahmad

    2004-01-01

    Progressive peri-implanter bone losses, which are accompanied by inflammatory process in the soft tissues is referred to as peri-implantitis. The aim of this study was to compare the effects of lethal photosensitisation with the conventional technique on bacterial reduction in ligature induced peri-implantitis in dogs. Seventeen third pre-molars of Labrador dogs were extracted and, immediately after, the implants were submerged. After osteointegration, peri-implantitis was induced. After 4 months, ligature were removed and the same period was waited for natural induction of bacterial plaque. The dogs were randomly divided into two groups. In the conventional group, they were treated with the conventional techniques of mucoperiosteal flaps for scaling the implant surface and irrigate it. In the laser group, only mucoperiosteal scaling was carried out before photodynamic therapy. On the peri-implanter pocket an azulene paste was injected and a GaAlAs low-power laser (λ= 660 nm, P= 30 mW, E= 5,4 J and Δt= 3 min.). Microbiological samples were obtained before and immediately after treatment. One implant was removed to be analyzed by scan electron microscopy to verify contamination on the implant surface. The results of this study showed that Prevotella sp., Fusobacterium e S. Beta-haemolyticus were significantly reduced for the conventional and laser groups. (author)

  14. Photodynamic therapy of bladder cancer - a phase I study using hexaminolevulinate (HAL).

    Science.gov (United States)

    Bader, M J; Stepp, Herbert; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Kriegmair, Martin; Zaak, Dirk; Welschof, Mona; Tilki, Derya; Stief, Christian G; Waidelich, Raphaela

    2013-10-01

    To assess the safety and feasibility of hexaminolevulinate (HAL) based photodynamic therapy (PDT) as adjuvant treatment after transurethral resection of the bladder (TURB) in patients with intermediate or high-risk urothelial cell carcinoma (UCC) of the bladder. Seventeen patients received 50 ml of either a 16 mM (4 patients) or 8 mM HAL (13 patients) solution instilled intravesically. Bladder wall irradiation was performed using an incoherent white light source coupled via a quartz fiber assembled into a flexible transurethral irrigation catheter. Each patient received 3 treatments with HAL-PDT 6 weeks apart. After PDT, patients were followed by regular cystoscopy for up to 21 months to assess time to recurrence. Reported adverse events (AEs) were coded according the World Health Organization Adverse Reaction Terminology (WHO-ART). Efficacy was assessed by cystoscopy, cytology, and histology, and was defined as the number of patients who were tumor-free at 6 or 21 months after initial PDT treatment. Transient bladder irritability was reported by 15 of the 17 patients and resolved completely in all patients. No evidence of a cumulative effect of treatment on the incidence of AEs could be detected. PDT treatment was performed without any technical complications. Furthermore preliminary assessment of efficacy showed that of the 17 patients included, 9 (52.9%; 95% CI: 27.8-77.0) were tumor-free at 6 months, 4 (23.5%; 95% CI: 6.8-49.9) were tumor-free at 9 months, and 2 (11.8%, 95% CI: 1.5-36.4) were tumor-free after 21 months. PDT using hexaminolevulinate and an incoherent white light system with the special flexible irradiation catheter system is technically feasible and safe and may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Photodynamic therapy: development of methods and clinical applications in FCI MRCC MOH

    Directory of Open Access Journals (Sweden)

    M. A. Kaplan

    2014-01-01

    Full Text Available This article is dedicated to clinical experience of photodynamic therapy (PDT in Medical Radiological Research Center. Authors represent the results of treatment in 156 patients with primary untreated tumors of different localizations as follows: basal cell skin cancer (BCSC in 156 patients, squamous cell carcinoma of the skin (SCCS in 24 patients, cancer of upper and lower lips in 30 patients. The other group of patients included recurrent and metastatic diseases: recurrent BCSC were in 127 patients, recurrent or continued growth of SCCS – in 27, recurrent or continued growth of lip cancer – in 13, intracutaneous metastases of skin melanoma (62 patients and breast cancer (46 – in 108. PDT was performed with photosensitizers Photosense (2.0 mg/kg, Photolon (0.9–2.5 mg/kg, and Photoditazine (0.7–0.8 mg/kg. The light irradiation dose was 100–600 J/cm2. After PDT of previously untreated BCSC the complete regression (CR of tumor lesions was in 96.8% of patients, partial regression (PR – in 3.2% of patients; for PDT of recurrent BCSC in 76.4% and 23.6%, respectively. After PDT treatment in patients with previously untreated SCCS CR of tumor lesions was achieved in 91.7% of patients, PR – in 8.3% of patients. For treatment of relapses in SCCS CR was achieved in 59.3% of cases, PR – in 33.3%, absence of regression was reported in 7.4% of cases. PDT of intracutaneous metastases of skin melanoma and breast cancer provided positive treatment effect (CR + PR + stabilizing in 95 and 98% of cases, respectively. CR in primary lip cancer after PDT was reported in 86.0% of patients, PR – in 14.0%. For PDT of recurrent lip cancer CR accounted for 69.2%, PR – 30.8%. 

  16. Nicotinamide augments the survival and incidence of apoptosis in glioma cells following photodynamic therapy in vitro

    Science.gov (United States)

    Bisland, Stuart K.; Modi, Nayan; Wilson, Brian C.

    2004-10-01

    The ability to customize photodynamic therapy (PDT) parameters with regards to timing and dosing of administered drug and light can be beneficial in determining target specificity and mode of cell death. Sustained, low level PDT or metronomic PDT (mPDT) may afford enhanced apoptotic cell death. This is of particular importance when considering PDT for the treatment of brain tumors as unlike apoptosis, necrotic cell death often leads to inflammation with increased intracranial pressure. The ability, therefore, to 'fine tune' PDT in favour of apoptosis is paramount. We have studied both acute (one time treatment) PDT (aPDT) and mPDT delivery strategies in combination with nicotinamide (NA) in an attempt to maximize the number of tumor cells dieing by apoptosis. Using several different glioma cell lines (9L, U87-MG and CNS-1) we now confirm that NA provides a dose-dependent (0.1-0.5 mM) increase in apoptotic cells following d-aminolevulinic acid-mediated aPDT or mPDT. Furthermore, using the 9L cell line stably transfected with the luciferase gene, NA was shown to delay the depletion of bioluminscence signal in aPDT and mPDT treated cells, inferring that adenosine triphosphate levels are maintained for longer following NA treatment. NA has previously been reported as promoting neuronal and vascular cell survival in normal brain following a number of neurological insults in which reactive oxygen species are implicated including, stroke, Alzheimer's disease and toxin-induced lesions. It is likely that the effects of NA reflect its capacity as an antioxidant as well as its ability to inhibit poly (adenosine diphosphate-ribose) polymerase-mediated depletion of ATP. Our results indicate that NA may prove therapeutically advantageous when used in combination with PDT treatment of brain tumors.

  17. In vitro evaluation of photodynamic therapy using redox-responsive nanoparticles carrying PpIX

    Science.gov (United States)

    Souza Leite, Ilaiáli; Vivero-Escoto, Juan L.; Lyles, Zachary; Salvador Bagnato, Vanderlei; Mayumi Inada, Natalia

    2018-02-01

    Photodynamic therapy (PDT) is a technique that combines light's interaction with a photoactive substance to promote cellular death and that has been used to treat a wide range of maladies. Cancer is among the leading causes of death worldwide and has been a central issue assessed by PDT research and clinical trials over the last 35 years, but its efficiency has been hampered by photosensitizer buildup at treatment site. Nanotechnology has been addressing drug delivery problems by the development of distinct nanostructured platforms capable of increasing pharmacological properties of molecules. The association of nanotechnology's potential to enhance photosensitizer delivery to target tissues with PDT's oxidative damage to induce cell death has been rising as a prospect to optimize cancer treatment. In this study, we aim to verify and compare the efficiency of PDT using redox-responsive silica-based nanoparticles carrying protoporphyrin IX (PpIX) in vitro, in both tumor and healthy cells. Dose-response experiments revealed the higher susceptibility of murine melanoma cells (B16-F10 cell line) to PDT (630 nm, 50 J/cm2) when compared to human dermal fibroblasts (HDFn): after 24 h of incubation with 50 μg/mL nanoparticles solutions, approximately 80 % of B16- F10 cells were killed, while similar results were obtained in HDFn cultures when solutions over 150 μg/mL were used. Uptake and ROS generation assays suggest increased nanoparticle internalization in the tumor cell line, in comparison with the healthy cells, and greater ROS levels were observed in B16-F10 cells.

  18. A new LED device used for photodynamic therapy in treatment of moderate to severe acne vulgaris.

    Science.gov (United States)

    Dong, Yiyun; Zhou, Guoyu; Chen, Jinan; Shen, Lingyue; Jianxin, Zhao; Xu, Qing; Zhu, Yulan

    2016-03-01

    This study investigated the efficacy and safety of a newly designed LED device used in photodiagnosis and photodynamic therapy of moderate to severe acne vulgaris in Chinese patients. Forty-six patients with moderate to severe facial acne showing high degrees of fluorescence by ultraviolet light examination were illuminated during ALA-PDT with two wavelengths of light (543-548 nm, and 630±6 nm, respectively) after 2 h of incubation with ALA. Each patient received treatment once every 30 days for two or three sessions. Two independent investigators assigned an acne severity score at baseline, one week after each treatment, as well as 4, 8, and 12 weeks after the completion of treatment. Adverse effects were recorded during and after each treatment. All patients rated their satisfaction with the results of treatment at a 12-week follow up visit. The ALA-PDL treatment regimen showed an overall effectiveness rate of 89.13% (41/46 patients). Some degree of clinical efficacy was seen in 71.42%, 86.67%, and 95.83% of patients with grades IV, V, and VI acne, respectively, and the rate of clinical effectiveness increased with increasing acne severity. When compared with baseline scores, significant reductions in acne scores were obtained at 8, and 12 weeks after completion of treatment. Maximum efficacy was shown at the 12 week follow up. No severe adverse events were observed. ALA-PDT administered with the newly designed LED device was an effective treatment for moderate to severe acne vulgaris, and side effects were mild and reversible. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Hematoporphyrin monomethyl ether-mediated photodynamic therapy selectively kills sarcomas by inducing apoptosis.

    Directory of Open Access Journals (Sweden)

    Hui Zeng

    Full Text Available We investigated the antitumor effect and mechanism of hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT in sarcomas. Intracellular uptake of HMME by osteosarcoma cells (LM8 and K7 was time- and dose-dependent, while this was not observed for myoblast cells (C2C12 and fibroblast cells (NIH/3T3. HMME-PDT markedly inhibited the proliferation of sarcoma cell lines (LM8, MG63, Saos-2, SW1353, TC71, and RD (P<0.05, and the killing effect was improved with increased HMME concentration and energy intensity. Flow cytometry analysis revealed that LM8, MG63, and Saos-2 cells underwent apoptosis after treatment with HMME-PDT. Additionally, apoptosis was induced after HMME-PDT in a three-dimensional culture of osteosarcoma cells. Hoechst 33342 staining confirmed apoptosis. Cell death caused by PDT was rescued by an irreversible inhibitor (Z-VAD-FMK of caspase. However, cell viability was not markedly decreased compared with the HMME-PDT group. Expression levels of caspase-1, caspase-3, caspase-6, caspase-9, and poly (ADP-ribose polymerase (PARP proteins were markedly up-regulated in the treatment groups and increased with HMME concentration as determined by western blot analysis. In vivo, tumor volume markedly decreased at 7-16 days post-PDT. Hematoxylin and eosin staining revealed widespread necrotic and infiltrative inflammatory cells in the HMME-PDT group. Immunohistochemistry analysis also showed that caspase-1, caspase-3, caspase-6, caspase-9, and PARP proteins were significantly increased in the HMME-PDT group. These results indicate that HMME-PDT has a potent killing effect on osteosarcoma cells in vitro and significantly inhibits tumor growth in vivo, which is associated with the caspase-dependent pathway.

  20. Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

    Science.gov (United States)

    Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

    2005-04-01

    During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

  1. Photodynamic therapy on bacterial reduction in dental caries: in vivo study

    Science.gov (United States)

    Baptista, Alessandra; Araujo Prates, Renato; Kato, Ilka Tiemy; Amaral, Marcello Magri; Zanardi de Freitas, Anderson; Simões Ribeiro, Martha

    2010-04-01

    The reduction of pathogenic microorganisms in supragingival plaque is one of the principal factors in caries prevention and control. A large number of microorganisms have been reported to be inactivated in vitro by photodynamic therapy (PDT). The purpose of this study was to develop a rat model to investigate the effects of PDT on bacterial reduction in induced dental caries. Twenty four rats were orally inoculated with Streptococcus mutans cells (ATCC 25175) for three consecutive days. The animals were fed with a cariogenic diet and water with 10% of sucrose ad libitum, during all experimental period. Caries lesion formation was confirmed by Optical Coherence Tomography (OCT) 5 days after the beginning of the experiment. Then, the animals were randomly divided into two groups: Control Group: twelve animals were untreated by either light or photosensitizer; and PDT Group: twelve animals were treated with 100μM of methylene blue for 5min and irradiated by a Light Emitting Diode (LED) at λ = 640+/-30nm, fluence of 172J/cm2, output power of 240mW, and exposure time of 3min. Microbiological samples were collected before, immediately after, 3, 7 and 10 days after treatment and the number of total microaerophiles was counted. OCT images showed areas of enamel demineralization on rat molars. Microbiological analysis showed a significant bacterial reduction after PDT. Furthermore, the number of total microaerophiles in PDT group remained lower than control group until 10 days posttreatment. These findings suggest that PDT could be an alternative approach to reduce bacteria in dental caries.

  2. Development and evaluation of zinc phthalocyanine nanoemulsions for use in photodynamic therapy for Leishmania spp.

    Science.gov (United States)

    Betzler de Oliveira de Siqueira, Luciana; da Silva Cardoso, Verônica; Almeida Rodrigues, Igor; Lúcia Vazquez-Villa, Ana; Pereira dos Santos, Elisabete; da Costa Leal Ribeiro Guimarães, Bruno; dos Santos Cerqueira Coutinho, Cristal; Vermelho, Alane Beatriz; Ricci Junior, Eduardo

    2017-02-01

    Photodynamic therapy (PDT) combines light with photosensitizers (PS) for production of reactive oxygen species (ROS) that can kill infectious microorganisms such as bacteria, fungi and protozoa. The application of nanotechnology has enabled the advancement of PDT because many PS are insoluble in water, necessitating a nanocarrier as a physiologically acceptable carrier. Nanoemulsions are efficient nanocarriers for solubilizing liposoluble drugs, like the PS, in water. Cutaneous (CL) and mucocutaneous leishmaniasis (ML) are caused by different species of the genus Leishmania, transmitted to humans by sandfly bites. Parasites are hosted in skin macrophages producing ulcerative lesions. Thus, a topical treatment, effective and inexpensive, for CL and ML is preferable to systemic interventions. There are topical treatments like paromomycin and amphotericin B, but they have many local side effects or a very high cost, limiting their use. This work aimed to develop a zinc phthalocyanine (photosensitizer) oil-in-water nanoemulsion, essential clove oil and polymeric surfactant (Pluronic® F127) for the formulation of a topical delivery system for use in PDT against Leishmania amazonensis and Leishmania infantum. The nanoemulsion was produced by a high-energy method and characterized by size, polydispersity, morphology, pH, content and stability studies. The toxicity in the dark and the photobiological activity of the formulations were evaluated in vitro for Leishmania and macrophages. The formulation presented was pH compatible with topical use, approximately 30 nm in size, with a polydispersity index ≤0.1 and remained stable at room and refrigerator temperature during the stability study (60 days). The zinc phthalocyanine nanoemulsion is effective in PDT against Leishmania spp.; use against skin infections can be a future application of this topical formulation, avoiding the use of oral or injectable medications, decreasing systemic adverse effects.

  3. Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer

    International Nuclear Information System (INIS)

    Rollakanti, Kishore R; Anand, Sanjay; Maytin, Edward V

    2015-01-01

    Cutaneous metastasis occurs more frequently in breast cancer than in any other malignancy in women, causing significant morbidity. Photodynamic therapy (PDT), which combines a porphyrin-based photosensitizer and activation by light, can be employed for breast cancer (especially cutaneous metastases) but tumor control after PDT has not surpassed traditional treatments methods such as surgery, radiation, and chemotherapy up to now. Here, we report that breast cancer nodules in mice can be effectively treated by preconditioning the tumors with 1α, 25-dihydroxyvitamin D 3 (calcitriol; Vit D) prior to administering 5-aminolevulinate (ALA)-based PDT. Breast carcinoma tumors (MDA-MB-231 cells implanted subcutaneously in nude mice) received systemic Vit D (1 μg/kg) for 3 days prior to receiving ALA. The addition of Vit D increased intratumoral accumulation of protoporphyrin IX (PpIX) by 3.3 ± 0.5-fold, relative to mice receiving ALA alone. Bioluminescence imaging in vivo and immunohistochemical staining confirmed that tumor-specific cell death after ALA-PDT was markedly enhanced (36.8 ± 7.4-fold increase in TUNEL-positive nuclei; radiance decreased to 14% of control) in Vit D pretreated tumors as compared to vehicle-pretreated tumors. Vit D stimulated proliferation (10.7 ± 2.8-fold) and differentiation (9.62 ± 1.7-fold) in tumor cells, underlying an augmented cellular sensitivity to ALA-PDT. The observed enhancement of tumor responses to ALA-PDT after low, nontoxic doses of Vit D supports a new combination approach that deserves consideration in the clinical setting, and offers potential for improved remission of cutaneous breast cancer metastases

  4. Riboflavin acetate induces apoptosis in squamous carcinoma cells after photodynamic therapy.

    Science.gov (United States)

    Juarez, Andrea V; Sosa, Liliana Del V; De Paul, Ana L; Costa, Ana Paula; Farina, Marcelo; Leal, Rodrigo B; Torres, Alicia I; Pons, Patricia

    2015-12-01

    Several research efforts have been focused on finding newer and more efficient photosensitizers for photodynamic therapy (PDT). Although, it was demonstrated that riboflavin is an efficient photosensitizer for PDT, the effect of its ester derivate, riboflavin 2',3',4',5'-tetraacetate (RFTA), which has higher cellular uptake, has not been well defined. To evaluate the cell death generated by applying RFTA as the photosensitizer in PDT in a human cancer cell line of squamous carcinoma (SCC-13), these cells were incubated with riboflavin and its ester derivate, RFTA followed by irradiation with different blue light doses. Cell viability was evaluated using neutral red uptake assay and cell death was evaluated using transmission electron microscopy, TUNEL assay and annexin V-PE/7AAD double staining. The expression of caspase-3, Bax, Bcl-2, ERK 1/2 and p38(MAPK) was evaluated by Western blotting and generation of intracellular ROS and changes in anion superoxide levels were analyzed using 2',7'-dichlorofluorescein-diacetate and dihydroethidium dye, respectively. RFTA-PDT generated a decrease in cancer cell viability in a light dose-response. Treated SCC-13 cells exhibited chromatin condensation, formation of apoptotic bodies, increases in TUNEL-positive cells, phosphatidylserine externalization and decreased procaspase-3 and Bcl-2 protein expression and increment of ERK 1/2 phosphorylation. Moreover, trolox abolished the effect of PDT on cell viability linking the increase in intracellular ROS levels with the cell death observed, whereas that the pre-treatment with MEK inhibitor did not induce changes in SCC-13 cell survival. These findings demonstrate the effects of RFTA in triggering apoptosis induced by ROS (\\O2(-)) production after visible light irradiation of squamous carcinoma cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Effects of periodontitis on the development of asthma: The role of photodynamic therapy.

    Science.gov (United States)

    Candeo, Larissa Carbonera; Rigonato-Oliveira, Nicole Cristine; Brito, Aurileia Aparecida; Marcos, Rodrigo Labat; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Bussadori, Sandra Kalil; Vieira, Rodolfo Paula; Lino-Dos-Santos-Franco, Adriana; Ligeiro-Oliveira, Ana Paula; Horliana, Anna Carolina Ratto Tempestini

    2017-01-01

    To evaluate whether periodontitis modulates lung inflammation in an experimental model of asthma as well as the photodynamic therapy (PDT) is associated with a reduction of lung inflammation. Seventy-two BALB/c male mice (~2 months) were randomly divided into 8 groups (n = 9): Basal, Periodontitis (P), P+PT, P+PT+PDT, Asthma (A), A+P, A+P+PT, and A+P+PT+PDT. Periodontitis was induced by using the ligature technique and asthma was induced by ovalbumin (OVA). PT was performed with curettes and PDT with methylene blue (0.005%), λ = 660nm, with a radiant exposure of 318J/cm2. After 43 days, euthanasia was carried out prior to lung and mandible morphological analyzes. All of the manipulations of the animals were performed by only one operator. The total and differential cell counts and cytokines IL-4, IL-5, IL-10, IFN-γ, TNF-α, IL-1β, and IL-6 were evaluated in the bronchoalveolar lavage (BAL) and in the serum. Mucus and alkaline phosphatase were also quantified. Statistical analyzes were performed by a blinded statistician. One-way analysis of variance (ANOVA) was employed, followed by the Student-Newman-Keuls test. Periodontitis group (P) increased alkaline phosphatase and bone resorption (pperiodontitis. The A group and the P group increased the total amount of cells (p periodontitis in the asthmatic mice reduced the inflammatory migrated cells in the BAL (eosinophils, lymphocytes, macrophages). In addition, it reduced the levels of the IL-4 and TNF-α cytokines, which was also accompanied by a decreased mucus production. After PDT treatment the total cell count increased however, this increase was not accompanied by a pro-inflammatory cytokines release. Only in PDT group the anti-inflammatory IL-10 was increased. Further studies are needed to understand this mechanism of action.

  6. Fricke dosimetry as a tool to quality control of photodynamic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Suzana O.; Souza, Vivianne L.B., E-mail: vlsouza@cnen.gov.br, E-mail: suzirecifeusa@hotmail.com [Centro Regional de Ciências Nucleares do Nordeste (CRNE-NE/CNEN-PE), Recife, PE (Brazil)

    2017-07-01

    Photodynamic therapy (PDT) consists of the association of a photosensitizing agent with a light source in order to cause cellular necrosis. Methylene blue, toluidine blue and malachite green are photosensitizers derived from dyes that are widely accepted in medicine, as they have low toxicity and are low cost. PDT is an alternative treatment for cancer, with significant advantages over procedures such as surgery/chemotherapy. Our laboratory has studied the Fricke solution doped with photosensitizers in an approach to obtain a quality control for PDT. The Fricke solution was prepared with ammoniacal ferrous sulfate, sodium chloride and sulfuric acid in water. The solutions modified with photosensitizers were prepared by adding 0.1 g/100 mL of the dyes. A volume of 2.6 ml of the Fricke solution modified with photosensitizers were transferred to test tubes and irradiated. The irradiated solutions had their optical densities measured in a spectrophotometer. The samples were irradiated with LED (Light Emitting Diodes) in acrylic phantoms. The FATA samples irradiated with LED showed the sensitivity of the dosimeters to red, blue, green and yellow light. A calibration curve with correlation coefficient of 0.9884 for the red light was obtained; 0.9752 for blue light; 0.9644 for the green light and 0.9768 for the yellow light. The fact that a sensitivity of the dosimeters to the LED has been occurred indicates that the PDT could be realized with LED, with lower costs than with laser. This work suggested that FATA dosimeters can be used for quality control of PDT. (author)

  7. The potential of photodynamic therapy to treat esophageal candidiasis coexisting with esophageal cancer.

    Science.gov (United States)

    Qiu, Haixia; Mao, Yongping; Gu, Ying; Zhu, Jianguo; Wang, Ying; Zeng, Jing; Huang, Naiyan; Liu, Qingsen; Yang, Yunsheng

    2014-01-05

    Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis. Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation. The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases. Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Mitochondrial targets of photodynamic therapy and their contribution to cell death

    Science.gov (United States)

    Oleinick, Nancy L.; Usuda, Jitsuo; Xue, Liang-yan; Azizuddin, Kashif; Chiu, Song-mao; Lam, Minh C.; Morris, Rachel L.; Nieminen, Anna-Liisa

    2002-06-01

    In response to photodynamic therapy (PDT), many cells in culture or within experimental tumors are eliminated by apoptosis. PDT with photosensitizers that localize in or target mitochondria, such as the phthalocyanine Pc 4, causes prompt release of cytochrome c into the cytoplasm and activation of caspases-9 and -3, among other caspases, that are responsible for initiating cell degradation. Some cells appear resistant to apoptosis after PDT; however, if they have sustained sufficient damage, they will die by a necrotic process or through a different apoptotic pathway. In the case of PDT, the distinction between apoptosis and necrosis may be less important than the mechanism that triggers both processes, since critical lethal damage appears to occur during treatment and does not require the major steps in apoptosis to be expressed. We earlier showed, for example, that human breast cancer MCF-7 cells that lack caspase-3 are resistant to the induction of apoptosis by PDT, but are just as sensitive to the loss of clonogenicity as MCF-7 cells stably expressing transfected procaspase-3. Many photosensitizers that target mitochondria specifically attack the anti-apoptotic protein Bcl-2, generating a variety of crosslinked and cleaved photoproducts. Recent evidence suggests that the closely related protein Bcl-xL is also a target of Pc 4-PDT. Transient transfection of an expression vector encoding deletion mutants of Bcl-2 have identified the critical sensitive site in the protein that is required for photodamage. This region contains two alpha helices that form a secondary membrane anchorage site and are thought to be responsible for pore formation by Bcl-2. As specific protein targets are identified, we are becoming better able to model the critical events in PDT-induced cell death.

  9. Local photodynamic therapy delays recurrence of equine periocular squamous cell carcinoma compared to cryotherapy.

    Science.gov (United States)

    Giuliano, Elizabeth A; Johnson, Philip J; Delgado, Cherlene; Pearce, Jacqueline W; Moore, Cecil P

    2014-07-01

    (i) To report the successful treatment of 10 cases of equine periocular squamous cell carcinoma (PSCC) with surgical excision and photodynamic therapy (PDT) using verteporfin. (ii) To evaluate time to first tumor recurrence between PDT-treated horses and horses treated with surgical excision and cryotherapy. A total of 24 equine PSCC cases were included: group 1 (n = 14) had excision and cryotherapy (1993–2003), group 2 (n = 10), excision and local PDT (2006–2010). Evaluated data: signalment, treatment method, tumor location, size, and time to first recurrence. Groups were compared via chi-square test for categorical variables and Wilcoxon rank-sum test for numeric variables. Time to tumor recurrence was examined using Kaplan–Meier product-limit survival analysis. Of 24 cases, nine breeds were affected. Mean age at treatment in years: 14 (range 5–24) in group 1; 11 (range 8–18) in group 2. Median tumor size: 163 mm2 (range 20–625 mm2) in group 1; 195 mm2 (range 45–775 mm2) in group 2. Signalment, tumor laterality, and size were not significantly different between groups. Time to recurrence was significantly different between groups (Logrank test, P = 0.0006). In group 1, 11/14 horses had tumor regrowth with median time to recurrence in months: 10 (range 1–44). In group 2 (minimum follow-up of 25 months; range 25–50), no horse demonstrated tumor recurrence after one treatment with excision and PDT. This represents the first report of local PDT using verteporfin for treatment of equine PSCC. Following surgery, the likelihood of tumor recurrence was significantly reduced with local PDT compared with cryotherapy. © 2013 American College of Veterinary Ophthalmologists.

  10. Porphyrin-based polysilsesquioxane nanoparticles to improve photodynamic therapy for cancer treatment

    Science.gov (United States)

    Vivero-Escoto, Juan L.; DeCillis, Daniel; Fritts, Laura; Vega, Daniel L.

    2014-03-01

    Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer treatment. The photosensitizer (PS) is perhaps the most critical component of PDT, and continues to be an area of intense scientific research. Traditionally, PS molecules (e.g. porphyrins) have dominated the field. Nevertheless, these PS agents have several disadvantages, with low water solubility, poor light absorption and reduced selectivity for targeted tissues being some of the main drawbacks. Polysilsesquioxane (PSilQ) nanoparticles are crosslinked homopolymers formed by the condensation of functionalized trialkoxysilanes or bis(trialkoxysilanes). We believe that PSilQ particles provide an interesting platform for developing PS nanocarriers. Several advantages can be foreseen by using this platform such as carrying a large payload of PS molecules; their surface and composition can be tailored to develop multifunctional systems (e.g. target-specific); and due to their small size, nanoparticles can penetrate deep into tissues and be readily internalized by cells. In this work, PSilQ nanoparticles with a high payload of photosensitizers were synthesized, characterized, and applied in vitro. The network of this nanomaterial is formed by protoporphyrin IX (PpIX) molecules chemically connected via a redox-responsive linker. Under reducing environment such as the one found in cancer cells the nanoparticles can be degraded to efficiently release single photosensitizers in the cytoplasm. The phototoxicity of this porphyrin-based PSilQ nanomaterial was successfully demonstrated in vitro using human cervical (HeLa) cancer cells. We envision that this platform can be further functionalized with polyethylene glycol (PEG) and targeting ligands to improve its biocompatibility and target specificity.

  11. Response Surface Methodology: An Extensive Potential to Optimize in vivo Photodynamic Therapy Conditions

    International Nuclear Information System (INIS)

    Tirand, Loraine; Bastogne, Thierry; Bechet, Denise M.Sc.; Linder, Michel; Thomas, Noemie; Frochot, Celine; Guillemin, Francois; Barberi-Heyob, Muriel

    2009-01-01

    Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as the response variable and was compared to tumor growth delay and relative tumor volumes. With only 13 experimental conditions tested, an optimal PDT condition was selected (PS agent dose, 2.80 mg/kg; fluence, 120 J/cm 2 ; fluence rate, 85 mW/cm 2 ). Treatment of glioma-bearing mice with the peptide-conjugated PS agent, followed by the optimized PDT condition showed a statistically significant improvement in delaying tumor growth compared with animals who received the PDT with the nonconjugated PS agent. Conclusions: Response surface methodology appears to be a useful experimental approach for rapid testing of different treatment conditions and determination of optimal values of PDT factors for any PS agent.

  12. Photodynamic therapy induces antifibrotic alterations in primary human vocal fold fibroblasts.

    Science.gov (United States)

    Zhang, Chi; Wang, Jiajia; Chou, Adriana; Gong, Ting; Devine, Erin E; Jiang, Jack J

    2018-04-18

    Photodynamic therapy (PDT) is a promising treatment modality for laryngeal dysplasia, early-stage carcinoma, and papilloma, and was reported to have the ability to preserve laryngeal function and voice quality without clinical fibrotic response. We aimed to investigate the mechanism behind the antifibrotic effects of PDT on primary human vocal fold fibroblasts (VFFs) in vitro. In vitro analysis from one human donor. Cell viability of VFFs in response to varying doses of PDT was investigated by the Cell Counting Kit-8 method. Sublethal-dose PDT (SL-PDT) was used for the following experiments. Expression of genes related to vocal fold extracellular matrix formation was analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Effects of PDT on cell migration, collagen contraction, and transforming growth factor β-1 (TGF-β1)-induced myofibroblast differentiation were also analyzed. PDT affects the viability of VFFs in a dose-dependent manner. SL-PDT significantly changed the expression profile of VFFs with antifibrotic effects. It also inhibited cell migration, reduced collagen contraction, and reversed the fibroblast-myofibroblast differentiation induced by TGF-β1. SL-PDT induces antifibrotic alterations in VFFs. This could explain the low incidence of vocal fold scar associated with PDT. Moreover, PDT may be useful in treating existing vocal fold scars. Further studies should focus on the in vivo effect of PDT on vocal fold wound healing and scar remodeling. NA Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Fricke dosimetry as a tool to quality control of photodynamic therapy

    International Nuclear Information System (INIS)

    Santos, Suzana O.; Souza, Vivianne L.B.

    2017-01-01

    Photodynamic therapy (PDT) consists of the association of a photosensitizing agent with a light source in order to cause cellular necrosis. Methylene blue, toluidine blue and malachite green are photosensitizers derived from dyes that are widely accepted in medicine, as they have low toxicity and are low cost. PDT is an alternative treatment for cancer, with significant advantages over procedures such as surgery/chemotherapy. Our laboratory has studied the Fricke solution doped with photosensitizers in an approach to obtain a quality control for PDT. The Fricke solution was prepared with ammoniacal ferrous sulfate, sodium chloride and sulfuric acid in water. The solutions modified with photosensitizers were prepared by adding 0.1 g/100 mL of the dyes. A volume of 2.6 ml of the Fricke solution modified with photosensitizers were transferred to test tubes and irradiated. The irradiated solutions had their optical densities measured in a spectrophotometer. The samples were irradiated with LED (Light Emitting Diodes) in acrylic phantoms. The FATA samples irradiated with LED showed the sensitivity of the dosimeters to red, blue, green and yellow light. A calibration curve with correlation coefficient of 0.9884 for the red light was obtained; 0.9752 for blue light; 0.9644 for the green light and 0.9768 for the yellow light. The fact that a sensitivity of the dosimeters to the LED has been occurred indicates that the PDT could be realized with LED, with lower costs than with laser. This work suggested that FATA dosimeters can be used for quality control of PDT. (author)

  14. Histologic changes associated with talaporfin sodium-mediated photodynamic therapy in rat skin.

    Science.gov (United States)

    Moy, Wesley J; Yao, Jonathan; de Feraudy, Sébastien M; White, Sean M; Salvador, Jocelynda; Kelly, Kristen M; Choi, Bernard

    2017-10-01

    Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a promising alternative treatment. To this end, we previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to understand treatment tissue effects to design a protocol that will achieve selective vascular injury without ulceration and scarring. The objective of this work is to assess skin changes associated with TS-mediated PDT with clinically relevant treatment parameters. We performed TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures were varied between 15 and 100 J/cm 2 . We took skin biopsies from subjects at 9 hours following PDT. We assessed the degree and depth of vascular and surrounding tissue injury using histology and immunohistochemical staining. TS-mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm 2 light doses resulted in vascular injury with minimal epidermal damage. At light dose of 50 J/cm 2 , epidermal damage was noted with vascular injury. At light doses >50 J/cm 2 , both vascular and surrounding tissue injury were observed in the forms of vasculitis, extravasated red blood cells, and coagulative necrosis. Extensive coagulative necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm 2 light doses. Observed depth of injury increased with increasing radiant exposure, although this relationship was not linear. TS-mediated PDT can cause selective vascular injury; however, at higher light doses, significant extra-vascular injury was observed. This information can be used to contribute to design of safe protocols to be used for treatment of cutaneous vascular lesions. Lasers Surg. Med. 49:767-772, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

    Science.gov (United States)

    Castano, Ana P.; Hamblin, Michael R.

    2006-02-01

    One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines

  16. Upconverting crystal/dextran-g-DOPE with high fluorescence stability for simultaneous photodynamic therapy and cell imaging

    International Nuclear Information System (INIS)

    Wang, HanJie; Wang, Sheng; Liu, Zhongyun; Dong, Chunhong; Chang, Jin; Yang, Jiumin; Gong, Xiaoqun

    2014-01-01

    To date, the application of photodynamic therapy in deep tissue has been severely restricted by the limited penetration depth of excitation light, such as UV light and visible light. In this work, a protocol of upconverting crystal/dextran-g-DOPE nanocomplex (UCN/dextran-g-DOPE) was developed. The nanocomplex was assembled from the hydrophobic upconverting nanoparticle (UCN) core and hydrophilic lipid shell. The photosensitizer zinc phthalocyanine (ZnPc) loaded UCN/dextran-g-DOPE offers possibilities to overcome the problem mentioned above. The UCN core works as a transducer to convert deeply penetrating near-infrared light to visible light to activate ZnPc for photodynamic therapy. The dextran-g-DOPE lipid shell is used for loading ZnPc and protecting the whole system from nonspecific absorbance or corrosion during the transportation. The experiment results show that the nanocomplex is an individual sphere with an average size of 30 nm. The ZnPc was activated to produce singlet oxygen successfully by the upconverting fluorescence emitted from UCN. The nanocomplex has high fluorescence stability in alkaline or neutral buffer solutions. Importantly, the ZnPc loaded UCN/dextran-g-DOPE nanocomplex showed a significant inhibitory effect on tumor cells after NIR exposure. Our data suggest that a ZnPc loaded UCN/dextran-g-DOPE nanocomplex may be a useful nanoplatform for future PDT treatment in deep-cancer therapy based on the upconverting mechanism. (paper)

  17. Studies on photodynamic mechanism of a novel chlorine derivative (TDPC and its antitumor effect for photodynamic therapy in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Ying Ye

    2015-01-01

    Full Text Available Photodynamic therapy (PDT represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer (PS play key roles in the treatment efficacy. In this study, a novel PS, 5,10,15,20-tetrakis((5-dipropylaminopentyl-chlorin (TDPC which displayed a characteristic long wavelength absorption peak at 650 nm were synthesized. It also shows a singlet oxygen generation rate of 4.257 min-1. Generally, TDPC is localized in mitochondria and nucleus of cell. After light irradiation with 650 nm laser, it can kill many types of cell, in addition, TDPC–PDT can destroy ECA-109 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following TDPC–PDT. The results showed that it either increased or decreased, among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. In general, TDPC is an effective antitumor PS in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new PSs.

  18. Changes in vaginal microbiota following antimicrobial and probiotic therapy

    Directory of Open Access Journals (Sweden)

    Jean M. Macklaim

    2015-08-01

    Full Text Available Background: The composition of the vaginal microbiota is known to be important for health. When infections occur, antimicrobial therapy is often poorly efficacious. Objective and design: We used 16S rRNA gene sequencing to characterize changes in the bacterial microbiota following oral antimicrobial and probiotic interventions. Results: While the bacterial vaginal profiles of women with vulvovaginal candidiasis were dominated by lactobacilli as in healthy women, and unchanged by therapy, Gardnerella vaginalis, Prevotella, Atopobium, Sneathia, and Megasphaera dominated the vagina of women with bacterial vaginosis (BV, and treatment with tinidazole plus Lactobacillus reuteri RC-14+L. rhamnosus GR-1 resulted in an increased relative abundance of indigenous L. iners or L. crispatus. Conclusions: The ability to restore homeostasis provides a rationale for conjoint use of probiotics with antibiotic treatment of BV.

  19. Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP.

    Science.gov (United States)

    Tsai, Shang-Ru; Yin, Rui; Huang, Ying-Ying; Sheu, Bor-Ching; Lee, Si-Chen; Hamblin, Michael R

    2015-03-01

    Low-level light therapy (LLLT) is used to stimulate healing, reduce pain and inflammation, and preserve tissue from dying. LLLT has been shown to protect cells in culture from dying after various cytotoxic insults, and LLLT is known to increase the cellular ATP content. Previous studies have demonstrated that maintaining a sufficiently high ATP level is necessary for the efficient induction and execution of apoptosis steps after photodynamic therapy (PDT). We asked whether LLLT would protect cells from cytotoxicity due to PDT, or conversely whether LLLT would enhance the efficacy of PDT mediated by mono-l-aspartyl chlorin(e6) (NPe6). Increased ATP could lead to enhanced cell uptake of NPe6 by the energy dependent process of endocytosis, and also to more efficient apoptosis. In this study, human osteosarcoma cell line MG-63 was subjected to 1.5J/cm(2) of 810nm near infrared radiation (NIR) followed by addition of 10μM NPe6 and after 2h incubation by 1.5J/cm(2) of 652nm red light for PDT. PDT combined with LLLT led to higher cell death and increased intracellular reactive oxygen species compared to PDT alone. The uptake of NPe6 was moderately increased by LLLT, and cellular ATP was increased. The mitochondrial respiratory chain inhibitor antimycin A abrogated the LLLT-induced increase in cytotoxicity. Taken together, these results demonstrate that LLLT potentiates NPe6-mediated PDT via increased ATP synthesis and is a potentially promising strategy that could be applied in clinical PDT. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Photodynamic synchrotron x-ray therapy in Glioma cell using superparamagnetic iron nanoparticle

    Science.gov (United States)

    Kim, Hong-Tae; Kim, Ki-Hong; Choi, Gi-Hwan; Jheon, Sanghoon; Park, Sung-Hwan; Kim, Bong-Il; Hyodo, Kazuyuki; Ando, Masami; Kim, Jong-Ki

    2009-06-01

    In order to evaluate cytotoxic effects of secondary Auger electron emission(Photon Activation Therapy:PAT) from alginate-coated iron nanoparticles(Alg-SNP), Alg-SNP-uptaken C6 glioma cell lines were irradiated with 6.89/7.2 Kev synchrotron X-ray. 0-125 Gy were irradiated on three experimental groups including No-SNP group incubating without SNP as control group, 6hr-SNP group incubating with SNP for 6hr and ON-SNP group incubating with SNP overnight. Irradiated cells were stained with Acridine Orange(AO) and Edithium Bromide(EB) to count their viability with fluorescent microscopy in comparison with control groups. AO stained in damaged DNA, giving FL color change in X-ray plus SNP group. EB did not or less enter inside the cell nucleus of control group. In contrast, EB entered inside the cell nucleus of Alg-SNP group which means more damage compared with Control groups. The results of MTT assay demonstrated a X-ray dose-dependent reduction generally in cell viability in the experimental groups. 3 or 9 times increase in cell survival loss rate was observed at 6hr-SNP and ON-SNP groups, respectively compared to No-SNP control group in first experiment that was done to test cell survival rate at relatively lower dose, from 0 to 50 Gy. In second experiment X-ray dose was increased to 125 Gy. Survival loss was sharply decreased in a relatively lower dose from 5 to 25 Gy, and then demonstrated an exponentially decreasing behavior with a convergence until 125 Gy for each group. This observation suggests PAT effects on the cell directly by X-ray in the presence of Alg-SNP occurs within lower X-ray dose, and conventional X-ray radiation effect becomes dominant in higher X-ray dose. The cell viability loss of ON-SNP group was three times higher compared with that of 6hr-SNP group. In conclusion, it is possible to design photodynamic X-ray therapy study using a monochromatic x-ray energy and metal nanoparticle as x-ray sensitizer, which may enable new X-ray PDT to