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Sample records for a-mediated photodynamic therapy

  1. 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...

  2. 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.

  3. [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.

  4. Photodynamic therapy in endodontics: a literature review.

    Science.gov (United States)

    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.

  5. 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

  6. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... 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 ...

  7. 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.

  8. mTHPC-mediated photodynamic diagnosis of malignant brain tumors

    International Nuclear Information System (INIS)

    Zimmermann, A.

    2001-03-01

    Radical tumor resection is the basis for prolonged survival of patients suffering from malignant brain tumors such as glioblastoma multiform. We have carried out a phase II study involving 22 patients with malignant brain tumors to assess the feasibility and the effectiveness of the combination of intraoperative photodynamic diagnosis (PDD) and fluorescence-guided resection (FGR) mediated by the second generation photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). In addition, intraoperative photodynamic therapy (PDT) was performed. Several commercially available fluorescence diagnostic systems were investigated for their applicability for clinical practice. We have adapted and optimized a diagnostic system which includes a surgical microscope, an excitation light source (filtered to 370-440 nm), a video camera detection system, and a spectrometer for clear identification of the mTHPC fluorescence emission at 652 nm. Especially in regions of faint fluorescence it turned out to be essential to maximize the spectral information by optimizing and matching the spectral properties of all components, such as excitation source, camera and color filters. In summary, based on 138 tissue samples derived from 22 tumor specimens we have been able to achieve a sensitivity of 87.9 % and a specificity of 95.7 %. This study demonstrates that mTHPC-mediated intraoperative fluorescence-guided resection followed by photodynamic therapy is a feasible concept. (author)

  9. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    Science.gov (United States)

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

    2015-03-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

  10. 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.

  11. 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.

  12. 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.

  13. Rose Bengal- and Riboflavin-Mediated Photodynamic Therapy to Inhibit Methicillin-Resistant Staphylococcus aureus Keratitis Isolates.

    Science.gov (United States)

    Halili, Francisco; Arboleda, Alejandro; Durkee, Heather; Taneja, Mukesh; Miller, Darlene; Alawa, Karam A; Aguilar, Mariela C; Amescua, Guillermo; Flynn, Harry W; Parel, Jean-Marie

    2016-06-01

    To evaluate the in vitro efficacy of rose bengal- and riboflavin-mediated photodynamic therapy for inhibition of methicillin-resistant Staphylococcus aureus (MRSA) isolates. Experimental study. Two different multidrug-resistant, clinical MRSA isolates were grown on nutrient agar, prepared in suspension, and adjusted to concentrations of 1.5 × 10(4) colony-forming units per milliliter. Bacterial suspensions were mixed with rose bengal, riboflavin, or water according to experimental group. Tested in triplicate, groups included: Group I, MRSA control; Group II, MRSA with 0.1% rose bengal; Group III, MRSA with 0.03% rose bengal; and Group IV, MRSA with 0.1% riboflavin. All experimental groups were exposed to 3 lighting conditions: dark, ambient room light for 30 minutes, and 5.4 J/cm(2) with either green light-emitting diode (LED) or ultraviolet-A (UV-A) irradiation. Plates were photographed at 72 hours and custom software measured bacterial growth inhibition. Complete growth inhibition of both MRSA strains was demonstrated (1) for both rose bengal concentrations under ambient and green LED irradiation, and (2) for the 0.1% rose bengal in the dark. The 0.03% rose bengal in dark conditions showed complete inhibition of strain 2 but incomplete inhibition of strain 1. Riboflavin showed almost complete inhibition with UV-A irradiation but demonstrated minimal inhibition for both strains in dark and ambient light conditions. Rose bengal- and riboflavin-mediated photodynamic therapy demonstrated complete growth inhibition in vitro of 2 multidrug-resistant MRSA strains. Rose bengal was also effective in dark and ambient conditions. These results may have implications for in vivo therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

    OpenAIRE

    Deng-Fu Yang; Jeng-Woei Lee; Hsin-Ming Chen; Yih-Chih Hsu

    2014-01-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Methods: Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical A...

  5. 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...

  6. 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

  7. 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)

  8. 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

  9. Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

    Directory of Open Access Journals (Sweden)

    Wang X

    2015-01-01

    Full Text Available Xiaojie Wang,1,2,* Lei Shi,2,* Qingfeng Tu,2 Hongwei Wang,3 Haiyan Zhang,2 Peiru Wang,2 Linglin Zhang,2 Zheng Huang,4 Feng Zhao,5 Hansen Luan,5 Xiuli Wang2 1Shanghai Skin Diseases Clinical College of Anhui Medical University, 2Shanghai Skin Disease Hospital, 3Huadong Hospital, Fudan University, Shanghai, 4MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, 5National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People’s Republic of China *These authors contributed equally to this study Background: Squamous cell carcinoma (SCC is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP-assisted 5-aminolevulinic acid (ALA delivery for topical photodynamic therapy (PDT of cutaneous SCC.Materials and methods: Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined.Results: PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC.Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC. Keywords: 5-aminolevulinic acid (ALA, polylactic-co-glycolic acid (PLGA, nanoparticles (NPs, cutaneous squamous cell carcinoma (SCC, photodynamic therapy (PDT, microneedling

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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 therapya 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.

  20. 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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp

    DEFF Research Database (Denmark)

    Wiegell, Stine; Fabricius, S; Stender, I M

    2011-01-01

    Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage, the inconvenie......, the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. Daylight-mediated PDT could potentially reduce these and may serve as an alternative to conventional PDT....

  8. 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.

  9. The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human Endometrial Adenocarcinoma Cell Line HEC-1-A.

    Science.gov (United States)

    Kim, Su-Mi; Rhee, Yun-Hee; Kim, Jong-Soo

    2017-11-01

    We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line. To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis. PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF. The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. 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.

  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. 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

  13. 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...

  14. 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.

  15. 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.

  16. 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 ...

  17. ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143.

    Science.gov (United States)

    Abdel Gaber, Sara A; Müller, Patricia; Zimmermann, Wolfgang; Hüttenberger, Dirk; Wittig, Rainer; Abdel Kader, Mahmoud H; Stepp, Herbert

    2018-01-01

    Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT. Accumulation of chlorin e6 in wild type U87 and doxycycline-inducible U251 glioblastoma cells with or without induction of ABCG2 expression or ABCG2 inhibition by KO143 was analyzed using flow cytometry. In U251 cells, ABCG2 was inducible by doxycycline after stable transfection with a tet-on expression plasmid. Tumor sphere cultivation under low attachment conditions was used to enrich for cells with stem cell-like properties. PDT was done on monolayer cell cultures by irradiation with laser light at 665nm. Elevated levels of ABCG2 in U87 cells grown as tumor spheres or in U251 cells after ABCG2 induction led to a 6-fold lower accumulation of chlorin e6 and the light dose needed to reduce cell viability by 50% (LD50) was 2.5 to 4-fold higher. Both accumulation and PDT response can be restored by KO143, an efficient non-toxic inhibitor of ABCG2. Glioblastoma stem cells might escape phototoxic destruction by ABCG2-mediated reduction of photosensitizer accumulation. Inhibition of ABCG2 during photosensitizer accumulation and irradiation promises to restore full susceptibility of this crucial tumor cell population to photodynamic treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Spanish-Portuguese consensus statement on use of daylight-mediated photodynamic therapy with methyl aminolevulinate in the treatment of actinic keratosis.

    Science.gov (United States)

    Gilaberte, Y; Aguilar, M; Almagro, M; Correia, O; Guillén, C; Harto, A; Pérez-García, B; Pérez-Pérez, L; Redondo, P; Sánchez-Carpintero, I; Serra-Guillén, C; Valladares, L M

    2015-10-01

    Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  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. 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.

  1. 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...

  2. 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

  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. 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.

  5. 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.

  6. 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.

  7. Continuous ultra-low-intensity artificial daylight is not as effective as red LED light in photodynamic therapy of multiple actinic keratoses

    DEFF Research Database (Denmark)

    Wiegell, Stine Regin; Heydenreich, Jakob; Fabricius, Susanne

    2011-01-01

    Daylight-mediated photodynamic therapy (PDT) is a simple and tolerable treatment of nonmelanoma skin cancer. It is of interest which light intensity is sufficient to prevent accumulation of protoporphyrin IX (PpIX) and effectively treat actinic keratoses (AKs). We compared the efficacy of PDT...

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. 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

  13. 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:...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. A Multimodal System with Synergistic Effects of Magneto-Mechanical, Photothermal, Photodynamic and Chemo Therapies of Cancer in Graphene-Quantum Dot-Coated Hollow Magnetic Nanospheres.

    Science.gov (United States)

    Wo, Fangjie; Xu, Rujiao; Shao, Yuxiang; Zhang, Zheyu; Chu, Maoquan; Shi, Donglu; Liu, Shupeng

    2016-01-01

    In this study, a multimodal therapeutic system was shown to be much more lethal in cancer cell killing compared to a single means of nano therapy, be it photothermal or photodynamic. Hollow magnetic nanospheres (HMNSs) were designed and synthesized for the synergistic effects of both magneto-mechanical and photothermal cancer therapy. By these combined stimuli, the cancer cells were structurally and physically destroyed with the morphological characteristics distinctively different from those by other therapeutics. HMNSs were also coated with the silica shells and conjugated with carboxylated graphene quantum dots (GQDs) as a core-shell composite: HMNS/SiO2/GQDs. The composite was further loaded with an anticancer drug doxorubicin (DOX) and stabilized with liposomes. The multimodal system was able to kill cancer cells with four different therapeutic mechanisms in a synergetic and multilateral fashion, namely, the magnetic field-mediated mechanical stimulation, photothermal damage, photodynamic toxicity, and chemotherapy. The unique nanocomposites with combined mechanical, chemo, and physical effects will provide an alternative strategy for highly improved cancer therapy efficiency.

  13. 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).

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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,

  1. 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.

  2. 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...

  3. 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.

  4. 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

  5. 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...

  6. Clinical, Radiographic and Microbiological Evaluation of High Level Laser Therapy, a New Photodynamic Therapy Protocol, in Peri-Implantitis Treatment; a Pilot Experience

    Directory of Open Access Journals (Sweden)

    Gianluigi Caccianiga

    2016-01-01

    Full Text Available Aim. Endosseous implants are widely used to replace missing teeth but mucositis and peri-implantitis are the most frequent long-term complications related with dental implants. Removing all bacterial deposits on contaminated implant surface is very difficult due to implant surface morphology. The aim of this study was to evaluate the bactericidal potential of photodynamic therapy by using a new high level laser irradiation protocol associated with hydrogen peroxide in peri-implantitis. Materials and Methods. 10 patients affected by peri-implantitis were selected for this study. Medical history, photographic documentation, periodontal examination, and periapical radiographs were collected at baseline and 6 months after surgery. Microbiological analysis was performed with PCR Real Time. Each patient underwent nonsurgical periodontal therapy and surgery combined with photodynamic therapy according to High Level Laser Therapy protocol. Results. All peri-implant pockets were treated successfully, without having any complication and not showing significant differences in results. All clinical parameters showed an improvement, with a decrease of Plaque Index (average decrease of 65%, range 23–86%, bleeding on probing (average decrease of 66%, range 26–80%, and probing depth (average decrease of 1,6 mm, range 0,46–2,6 mm. Periapical radiographs at 6 months after surgery showed a complete radiographic filling of peri-implant defect around implants treated. Results showed a decrease of total bacterial count and of all bacterial species, except for Eikenella corrodens, 6 months after surgery. Conclusion. Photodynamic therapy using HLLT appears to be a good adjunct to surgical treatment of peri-implantitis.

  7. 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...

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. The effect of a novel photodynamic activation method mediated by curcumin on oyster shelf life and quality.

    Science.gov (United States)

    Liu, Fang; Li, Zhaojie; Cao, Binbin; Wu, Juan; Wang, Yuming; Xue, Yong; Xu, Jie; Xue, Changhu; Tang, Qing Juan

    2016-09-01

    In this paper, the effect of photodynamic method mediated by curcumin (PDT) on the shelf life and quality of pacific oysters during storage at 5±1°C were analyzed. In our previous study we investigated the optimal treatment conditions of photodynamic method mediated by curcumin to sterilization were 10uM photosensitizer concentration and 5.4J/cm 2 light energy density. Under these conditions, the effect of a novel photodynamic activation method mediated by curcumin on oyster shelf life and quality was researched. The total bacterial counts, TVB-N content and sensory analysis were used to evaluate the effects on oyster shelf life. The oyster shelf life was prolonged from 8days to 12days after photodynamic treatment and the oysters in the treatment group displayed notable odor retention, produced fewer odor corrupting substances when the control group oysters reached the end of their shelf life (day 8). Texture, free amino acid contents and fatty acid levels were applied to estimate the quality of the treated oysters. The texture had no significant change after treated with PDT. At the end of oyster shelf life, compared PDT group (PDT) with control group (control), total free amino acid contents (control: 234.30mg/100g, PDT: 813.02mg/100g) was higher and free fatty acid levels (control: 0.071mEq/L, PDT: 0.0455mEq/L) displayed lower in PDT group. This indicated that the treated oysters oxidized minimally, decayed slowly, decomposed fewer nutrients and had lower metabolic levels of spoilage microorganisms. PDT has a positive effect on prolonging oyster shelf life and its quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

    Full Text Available Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA-mediated photodynamic therapy (PDT to treat oral precancers including oral leukoplakia (OL, oral erythroleukoplakia (OEL, and oral verrucous hyperplasia (OVH as well as oral cancers including oral verrucous carcinoma (OVC and oral squamous cell carcinoma (OSCC. Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2 was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2 on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for

  16. 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.

  17. 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.

  18. Apoptosis and autophagy induced by pyropheophorbide-α methyl ester-mediated photodynamic therapy in human osteosarcoma MG-63 cells.

    Science.gov (United States)

    Huang, Qiu; Ou, Yun-Sheng; Tao, Yong; Yin, Hang; Tu, Ping-Hua

    2016-06-01

    Pyropheophorbide-α methyl ester (MPPa) was a second-generation photosensitizer with many potential applications. Here, we explored the impact of MPPa-mediated photodynamic therapy (MPPa-PDT) on the apoptosis and autophagy of human osteosarcoma (MG-63) cells as well as the relationships between apoptosis and autophagy of the cells, and investigated the related molecular mechanisms. We found that MPPa-PDT demonstrated the ability to inhibit MG-63 cell viability in an MPPa concentration- and light dose-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, MPPa-PDT could also induce autophagy of MG-63 cell. Meanwhile, the ROS scavenger N-acetyl-L-cysteine (NAC) and the Jnk inhibitor SP600125 were found to inhibit the MPPa-PDT-induced autophagy, and NAC could also inhibit Jnk phosphorylation. Furthermore, pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine showed the potential in reducing the apoptosis rate induced by MPPa-PDT in MG-63 cells. Our results indicated that the mitochondrial pathway was involved in MPPa-PDT-induced apoptosis of MG-63 cells. Meanwhile the ROS-Jnk signaling pathway was involved in MPPa-PDT-induced autophagy, which further promoted the apoptosis in MG-63 cells.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  10. 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...

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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....

  17. 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.

  18. 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.

  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 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.

  1. 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.

  2. Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy.

    Science.gov (United States)

    Yuan, Youyong; Liu, Bin

    2014-09-10

    A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 μg mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 μg mL(-1)) or chemotherapy (132.8 μg mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin αvβ3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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)

  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. Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

    Science.gov (United States)

    Kim, Michele M.; Penjweini, Rozhin; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

  11. 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.

  12. 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- ...

  13. 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 ...

  14. 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...

  15. 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

  16. 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.

  17. 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.

  18. Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

    Science.gov (United States)

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

  19. 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...

  20. "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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma

    Directory of Open Access Journals (Sweden)

    Wang M

    2017-05-01

    Full Text Available Mian Wang,1 Benjamin M Geilich,2 Michael Keidar,3 Thomas J Webster1,4 1Department of Chemical Engineering, 2Department of Bioengineering, Northeastern University, Boston, MA, 3Department of Mechanical and Aerospace Engineering, George Washington University, Washington, DC, USA; 4Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Traditional cancer treatments contain several limitations such as incomplete ablation and multidrug resistance. It is known that photodynamic therapy (PDT is an effective treatment for several tumor types especially melanoma cells. During the PDT process, protoporphyrin IX (PpIX, an effective photosensitizer, can selectively kill cancer cells by activating a special light source. When tumor cells encapsulate a photosensitizer, they can be easily excited into an excited state by a light source. In this study, cold atmospheric plasma (CAP was used as a novel light source. Results of some studies have showed that cancer cells can be effectively killed by using either a light source or an individual treatment due to the generation of reactive oxygen species and electrons from a wide range of wavelengths, which suggest that CAP can act as a potential light source for anticancer applications compared with UV light sources. Results of the present in vitro study indicated for the first time that PpIX can be successfully loaded into polymersomes. Most importantly, cell viability studies revealed that PpIX-loaded polymersomes had a low toxicity to healthy fibroblasts (20% were killed at a concentration of 400 µg/mL, but they showed a great potential to selectively kill melanoma cells (almost 50% were killed. With the application of CAP posttreatment, melanoma cell viability significantly decreased (80% were killed compared to not using a light source (45% were killed or using a UV light source (65% were killed. In summary, these results indicated for the

  9. 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.

  10. 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

  11. 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

  12. 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).

  13. 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).

  14. 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.

  15. 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

  16. Long-pulsed dye laser versus long-pulsed dye laser-assisted photodynamic therapy for acne vulgaris: A randomized controlled trial

    DEFF Research Database (Denmark)

    Haedersdal, M.; Togsverd, K.; Wiegell, S.R.

    2008-01-01

    Background: Long-pulsed dye laser (LPDL)-assisted photodynamic therapy has been suggested to be superior to laser alone for acne vulgaris but no evidence is available. Objective: To evaluate the efficacy and safety of LPDL alone versus LPDL in photodynamic therapy with methylaminolevulinic acid...... (MAL-LPDL) for acne vulgaris. Methods: Fifteen patients received a series of 3 full-face LPDL treatments and half-face prelaser MAL treatments; the latter being randomly assigned to the left or right side. Results: Inflammatory lesions were reduced more on MAL-LPDL-treated than on LPDL-treated sides...... to draw conclusions about the efficacy of the LPDL, only about the efficacy of MAL-LPDL compared with LPDL alone. Conclusions: MAL-LPDL is slightly superior to LPDL for the treatment of inflammatory acne Udgivelsesdato: 2008/3...

  17. 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...

  18. 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

  19. 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

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

    Science.gov (United States)

    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.

  1. 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

  2. Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

    Science.gov (United States)

    Kusuzaki, Katsuyuki; Matsubara, Takao; Murata, Hiroaki; Logozzi, Mariantonia; Iessi, Elisabetta; Di Raimo, Rossella; Carta, Fabrizio; Supuran, Claudiu T; Fais, Stefano

    2017-12-01

    Photodynamic molecules represent an alternative approach for cancer therapy for their property (i) to be photo-reactive; (ii) to be not-toxic for target cells in absence of light; (iii) to accumulate specifically into tumour tissues; (iv) to be activable by a light beam only at the tumour site and (v) to exert cytotoxic activity against tumour cells. However, to date their clinical use is limited by the side effects elicited by systemic administration. Extracellular vesicles are endogenous nanosized-carriers that have been recently introduced as a natural delivery system for therapeutic molecules. We have recently shown the ability of human exosomes to deliver photodynamic molecules. Therefore, this review focussed on extracellular vesicles as a novel strategy for the delivery of photodynamic molecules at cancer sites. This completely new approach may enhance the delivery and decrease the toxicity of photodynamic molecules, therefore, represent the future for photodynamic therapy for cancer treatment.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Physical and mathematical modeling of antimicrobial photodynamic therapy

    Science.gov (United States)

    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.

  8. 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

  9. 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)

  10. Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

    Science.gov (United States)

    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

  11. 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.

  12. 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.

  13. 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...

  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. 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...

  16. Chlorophyll mediated photodynamic inactivation of blue laser on Streptococcus mutans

    Science.gov (United States)

    Astuti, Suryani Dyah; Zaidan, A.; Setiawati, Ernie Maduratna; Suhariningsih

    2016-03-01

    Photodynamic inactivation is an inactivation method in microbial pathogens that utilize light and photosensitizer. This study was conducted to investigate photodynamic inactivation effects of low intensity laser exposure with various dose energy on Streptococcus mutans bacteria. The photodynamic inactivation was achieved with the addition of chlorophyll as photosensitizers. To determine the survival percentage of Streptococcus mutans bacteria after laser exposure, the total plate count method was used. For this study, the wavelength of the laser is 405 nm and variables of energy doses are 1.44, 2.87, 4.31, 5.74, 7.18, and 8.61 in J/cm2. The results show that exposure to laser with energy dose of 7.18 J/cm2 has the best photodynamic inactivation with a decrease of 78% in Streptococcus

  17. [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.

  18. 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.

  19. A Novel Photosensitizer 31,131-phenylhydrazine -Mppa (BPHM and Its in Vitro Photodynamic Therapy against HeLa Cells

    Directory of Open Access Journals (Sweden)

    Wenting Li

    2016-04-01

    Full Text Available Photodynamic therapy (PDT has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-31,131 bisphenylhydrazone modified methyl pyropheophorbide-a (BPHM was designed and synthesized with the consideration that phenylhydrazone structure may extend absorption wavelength of methyl pyro-pheophorbide-a (Mppa, and make the photosensitizer potential in deep tumor treatment. The synthesis, spectral properties and in vitro photodynamic therapy (PDT against human HeLa cervical cancer cell line was studied. Methyl thiazolyl tetrazolium (MTT assay showed the title compound could achieve strong inhibition of cervical cancer cell viability under visible light (675 nm, 25 J/cm2. Cell uptake experiments were performed on HeLa cells. Morphological changes were examined and analyzed by fluorescent inverted microscope. In addition, the mechanism of the photochemical processes of PDT was investigated, which showed that the formation of singlet oxygen after treatment with PDT played a moderate important role.

  20. 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. 

  1. 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

  2. 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.

  3. 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

  4. 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)

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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...

  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. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.

    OpenAIRE

    Gyenge Emina Besic; Lüscher Daniel; Forny Patrick; Antoniol Martina; Geisberger Georg; Walt Heinrich; Patzke Greta; Maake Caroline

    2013-01-01

    The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso tetrahydroxyphenyl chlorin (mTHPC) derivative with focus on their 1:1 mixture on head and neck squamous cell carcinoma cell lines. Absorption excitation and photobleaching were monitored using fluorescence spectrometry showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo stability. Singlet oxyg...

  17. 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.

  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. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  11. Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Brian C. Wilson

    2015-01-01

    Full Text Available Excited-state singlet oxygen (1O2, generated during photodynamic therapy (PDT, is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC in an animal model comprising luciferase- and green fluorescent protein (GFP-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1O2 counts demonstrated clear correlation, indicating that 1O2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

  12. 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.

  13. 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%.

  14. 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.

  15. 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.

  16. 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.

  17. A Highly Efficient and Photostable Photosensitizer with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Anticancer Therapy.

    Science.gov (United States)

    Wu, Wenbo; Mao, Duo; Hu, Fang; Xu, Shidang; Chen, Chao; Zhang, Chong-Jing; Cheng, Xiamin; Yuan, Youyong; Ding, Dan; Kong, Deling; Liu, Bin

    2017-09-01

    Photodynamic therapy (PDT), which relies on photosensitizers (PS) and light to generate reactive oxygen species to kill cancer cells or bacteria, has attracted much attention in recent years. PSs with both bright emission and efficient singlet oxygen generation have also been used for image-guided PDT. However, simultaneously achieving effective 1 O 2 generation, long wavelength absorption, and stable near-infrared (NIR) emission with low dark toxicity in a single PS remains challenging. In addition, it is well known that when traditional PSs are made into nanoparticles, they encounter quenched fluorescence and reduced 1 O 2 production. In this contribution, these challenging issues have been successfully addressed through designing the first photostable photosensitizer with aggregation-induced NIR emission and very effective 1 O 2 generation in aggregate state. The yielded nanoparticles show very effective 1 O 2 generation, bright NIR fluorescence centered at 820 nm, excellent photostability, good biocompatibility, and negligible dark in vivo toxicity. Both in vitro and in vivo experiments prove that the nanoparticles are excellent candidates for image-guided photodynamic anticancer therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment of Actinic Keratoses: A Randomized Clinical Trial.

    Science.gov (United States)

    Petukhova, Tatyana A; Hassoun, Lauren A; Foolad, Negar; Barath, Mayanka; Sivamani, Raja K

    2017-07-01

    Photodynamic therapy (PDT) is an effective and cosmetically favorable treatment modality for actinic keratoses (AKs). However, prolonged incubation times and pain associated with treatment are burdensome to the patient and a hindrance to widespread use of PDT as standard field therapy for AK. To evaluate efficacy and pain associated with microneedle expedited PDT. The Microneedle Photodynamic Therapy II (MNPDT-II) study was a randomized, single-blinded, split-face controlled, 2-arm clinical trial. Thirty-three participants with AK on the face were recruited in a university dermatology outpatient clinic from 2015 to 2016, and 32 participants completed the study. Participants were randomized into 2 incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA) incubation times, after pretreatment with a microneedle roller (200 um) vs a sham roller. They were blinded to the laterality of microneedle and sham roller assignments. After incubation, they were exposed to blue light (Blu-U, Dusa Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2. The primary outcome was to quantitatively measure AK resolution, and the secondary outcome was to assess pain associated with microneedle pretreatment. Thirty-three individuals were recruited and randomized to either the 20-minute or the 10-minute incubation arm. Thirty-two participants completed the study with a mean follow-up time of 34.5 days in the 20-minute group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm, average AK clearance was 76% vs 58% on the sham side (P microneedle and sham sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK clearance for the microneedle pretreated side was 43% compared with 38% on the sham side (P = .66). Pain during the blue light exposure was not significantly different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21), respectively. Photodynamic therapy with microneedle pretreatment at

  3. 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

  4. 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

  5. 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)

  6. 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.

  7. 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)

  8. 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.

  9. A Novel Photosensitizer 3¹,13¹-phenylhydrazine -Mppa (BPHM) and Its in Vitro Photodynamic Therapy against HeLa Cells.

    Science.gov (United States)

    Li, Wenting; Tan, Guanghui; Cheng, Jianjun; Zhao, Lishuang; Wang, Zhiqiang; Jin, Yingxue

    2016-04-29

    Photodynamic therapy (PDT) has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa) has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-3¹,13¹ bisphenylhydrazone modified methyl pyropheophorbide-a (BPHM) was designed and synthesized with the consideration that phenylhydrazone structure may extend absorption wavelength of methyl pyro-pheophorbide-a (Mppa), and make the photosensitizer potential in deep tumor treatment. The synthesis, spectral properties and in vitro photodynamic therapy (PDT) against human HeLa cervical cancer cell line was studied. Methyl thiazolyl tetrazolium (MTT) assay showed the title compound could achieve strong inhibition of cervical cancer cell viability under visible light (675 nm, 25 J/cm²). Cell uptake experiments were performed on HeLa cells. Morphological changes were examined and analyzed by fluorescent inverted microscope. In addition, the mechanism of the photochemical processes of PDT was investigated, which showed that the formation of singlet oxygen after treatment with PDT played a moderate important role.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. 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.

  1. The effect of aloe emodin–encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells

    International Nuclear Information System (INIS)

    Li, Kai-Ting; Duan, Qin-Qin; Chen, Qing; He, Juan-Wen; Tian, Si; Lin, Hai-Dan; Gao, Qing; Bai, Ding-Qun

    2015-01-01

    Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)–encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm 2 ). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human

  2. Photodynamic action of the methylene blue: mutagenesis and sinergism

    International Nuclear Information System (INIS)

    Capella, M.A.M.

    1988-01-01

    Two aspects of photodynamic therapy were studied: the associated mutagenesis and the interactions with physical agents, in order to increase its biological effects. The photodynamic action with methylene blue in the mutagenesis and sinergism is studied. (L.M.J.)

  3. 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.

  4. 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

  5. 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)

  6. 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.

  7. 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.

  8. Photophysical Properties of Pheophorbide-a Derivatives and Their Photodynamic Therapeutic Effects on a Tumor Cell Line In Vitro

    Directory of Open Access Journals (Sweden)

    Kang-Kyun Wang

    2014-01-01

    Full Text Available Pheophorbide-a derivatives have been reported to be potential photosensitizers for photodynamic therapy (PDT. In this study, photophysics of pheophorbide-a derivatives (PaDs were investigated along with their photodynamic tumoricidal effect in vitro. PaDs were modified by changing the coil length and/or making the hydroxyl group (–OH substitutions. Their photophysical properties were studied by steady-state and time-resolved spectroscopic methods. The photodynamic tumoricidal effect was evaluated in the mouse breast cancer cell line (EMT6. Lifetime and quantum yield of fluorescence and quantum yields of triplet state and singlet oxygen were studied to determine the dynamic energy flow. The coil length of the substituted alkyl group did not significantly affect the spectroscopic properties. However, the substitution with the hydroxyl group increased the quantum yields of the triplet state and the singlet oxygen due to the enhanced intersystem crossing. In order to check the application possibility as a photodynamic therapy agent, the PaDs with hydroxyl group were studied for the cellular affinity and the photodynamic tumoricidal effect of EMT6. The results showed that the cellular affinity and the photodynamic tumoricidal effect of PaDs with the hydroxyl group depended on the coil-length of the substituted alkyl group.

  9. 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....

  10. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

    LENUS (Irish Health Repository)

    Byrne, A T

    2009-11-03

    Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

  11. 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.

  12. 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.

  13. Expression of complement and pentraxin proteins in acute phase response elicited by tumor photodynamic therapy: the engagement of adrenal hormones.

    Science.gov (United States)

    Merchant, Soroush; Huang, Naiyan; Korbelik, Mladen

    2010-12-01

    Treatment of solid tumors by photodynamic therapy (PDT) was recently shown to trigger a strong acute phase response. Using the mouse Lewis lung carcinoma (LLC) model, the present study examined complement and pentraxin proteins as PDT-induced acute phase reactants. The results show a distinct pattern of changes in the expression of genes encoding these proteins in the tumor, as well as host liver and spleen, following PDT mediated by photosensitizer Photofrin™. These changes were influenced by glucocorticoid hormones, as evidenced by transcriptional activation of glucocorticoid receptor and the upregulation of gene encoding this receptor. The expression of gene for glucocorticoid-induced zipper (GILZ) protein, whose activity is particularly susceptible to glucocorticoid regulation, was also changed in PDT-treated tumors. A direct demonstration that tumor PDT induces glucocorticoid hormone upregulation is provided by documenting elevated levels of serum corticosterone in mice bearing PDT-treated LLC tumors. Tumor response to PDT was negatively affected by blocking glucocorticoid receptor activity, which suggests that glucocorticoid hormones have a positive impact on the therapeutic outcome with this therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial

    DEFF Research Database (Denmark)

    Wiegell, S.R.; Haedersdal, M.; Eriksen, P.

    2009-01-01

    Background Photodynamic therapy (PDT) is an effective but time-consuming and often painful treatment for actinic keratosis (AK). Home-based daylight-PDT has the potential to facilitate treatment procedure and to reduce associated pain due to continuous activation of small amounts of porphyrins...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Fluorescence and Magnetic Resonance Dual-Modality Imaging-Guided Photothermal and Photodynamic Dual-Therapy with Magnetic Porphyrin-Metal Organic Framework Nanocomposites

    Science.gov (United States)

    Zhang, Hui; Li, Yu-Hao; Chen, Yang; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

    2017-03-01

    Phototherapy shows some unique advantages in clinical application, such as remote controllability, improved selectivity, and low bio-toxicity, than chemotherapy. In order to improve the safety and therapeutic efficacy, imaging-guided therapy seems particularly important because it integrates visible information to speculate the distribution and metabolism of the probe. Here we prepare biocompatible core-shell nanocomposites for dual-modality imaging-guided photothermal and photodynamic dual-therapy by the in situ growth of porphyrin-metal organic framework (PMOF) on Fe3O4@C core. Fe3O4@C core was used as T2-weighted magnetic resonance (MR) imaging and photothermal therapy (PTT) agent. The optical properties of porphyrin were well remained in PMOF, and PMOF was therefore selected for photodynamic therapy (PDT) and fluorescence imaging. Fluorescence and MR dual-modality imaging-guided PTT and PDT dual-therapy was confirmed with tumour-bearing mice as model. The high tumour accumulation of Fe3O4@C@PMOF and controllable light excitation at the tumour site achieved efficient cancer therapy, but low toxicity was observed to the normal tissues. The results demonstrated that Fe3O4@C@PMOF was a promising dual-imaging guided PTT and PDT dual-therapy platform for tumour diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity.

  2. 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).

  3. 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.

  4. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

    Science.gov (United States)

    Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

    2014-09-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%). We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

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

    Science.gov (United States)

    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.

  6. 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.

  7. 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)

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

    Science.gov (United States)

    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.

  9. 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%.

  10. Correlation between treatment time, photobleaching, inflammation and pain after photodynamic therapy with methyl aminolevulinate on tape-stripped skin in healthy volunteers

    DEFF Research Database (Denmark)

    Lerche, Catharina M; Fabricius, Susanne; Philipsen, Peter A

    2015-01-01

    Photodynamic therapy (PDT) is an attractive treatment option for skin diseases such as actinic keratosis, since large skin areas can be treated with high response rates and good cosmetic outcomes. Nevertheless inflammation and pain are still major side effects. The aim of this study was to invest......Photodynamic therapy (PDT) is an attractive treatment option for skin diseases such as actinic keratosis, since large skin areas can be treated with high response rates and good cosmetic outcomes. Nevertheless inflammation and pain are still major side effects. The aim of this study...... of PpIX and to avoid unspecific distribution. We propose a shorter PDT regimen, "Pulse PDT", comprising, for example 30 min incubation with MAL and illumination after 180 min, and we have planned a study of actinic keratosis and "Pulse PDT"....

  11. 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...

  12. 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.

  13. 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.

  14. Mechanism of enhanced responses after combination photodynamic therapy (cPDT) in carcinoma cells involves C/EBP-mediated transcriptional upregulation of the coproporphyrinogen oxidase (CPO) gene

    Science.gov (United States)

    Anand, Sanjay; Hasan, Tayyaba; Maytin, Edward V.

    2013-03-01

    Photodynamic therapy (PDT) with aminolevulinate (ALA) is widely accepted as an effective treatment for superficial carcinomas and pre-cancers. However, PDT is still suboptimal for deeper tumors, mainly due to inadequate ALA penetration and subsequent conversion to PpIX. We are interested in improving the effectiveness of photodynamic therapy (PDT) for deep tumors, using a combination approach (cPDT) in which target protoporphyrin (PpIX) levels are significantly enhanced by differentiation caused by giving Vitamin D or methotrexate (MTX) for 3 days prior to ALAPDT. In LNCaP and MEL cells, a strong correlation between inducible differentiation and expression of C/EBP transcription factors, as well as between differentiation and mRNA levels of CPO (a key heme-synthetic enzyme), indicates the possibility of CPO transcriptional regulation by the C/EBPs. Sequence analysis of the first 1300 base pairs of the murine CPO upstream region revealed 15 consensus C/EBP binding sites. Electrophoretic Mobility Shift Assays (EMSA) proved that these sites form specific complexes that have strong, moderate or weak affinities for C/EBPs. However, in the context of the full-length CPO promoter, inactivation of any type of site (strong or weak) reduced CPO promoter activity (luciferase assay) to nearly the same extent, suggesting cooperative interactions. A comparative analysis of murine and human CPO promoters revealed possible protein-protein interactions between C/EBPs and several neighboring transcription factors such as NFkB, Sp1, AP-1, CBP/p300 and CREB (an enhanceosome complex). Overall, these results confirm that C/EBP's are important for CPO expression via complex mechanisms which upregulate PpIX and enhance the outcome of cPDT.

  15. 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

  16. 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.

  17. Anti-tumor activities of a novel chlorin derivative for photodynamic therapy in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Li-Jun Zhang

    2015-01-01

    Full Text Available In this study, a novel photosensitizer meso-tetra (3-pyrrolidinomethyl-4-methoxyphenyl chlorin (TPMC was reported. It displays a characteristic long wavelength absorption peak at 656 nm and it shows a singlet oxygen quantum yield of 0.48. After light irradiation with 650 nm laser, it can kill Eca-109 and SMMC-7721 cells in vitro (25 mW/cm2, 1.2 to 3.6 J/cm2 and destroy Eca-109 tumor in nude mice (50 mW/cm2, 90 J/cm2. It has the perspective to be developed as a new anti-tumor drug in photodynamic therapy (PDT photodiagnosis, and deserves further investigation.

  18. 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.

  19. 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.

  20. Fiber-optic filter fluorometer for emission detection of Protoporphyrin IX and its direct precursors – A preliminary study for improved Photodynamic Therapy applications

    Directory of Open Access Journals (Sweden)

    Rainer Landes

    2018-03-01

    Full Text Available In this work we present first results of a laboratory manufactured filter-fluorometer to study differences in intensity and position of the main peaks of three porphyrins that appear during the Heme-Synthesis. Porphyrins play a major role in Photodynamic Therapy (PDT for cancer treatment. Within the Heme-Synthesis, Porphyrins such as Protoporphyrin IX (PPIX and its two precursors Coproporphyrin III (CPIII and Uroporphyrin III (UPIII represent photochemical agents that can interact with light to show fluorescence or generate Reactive Oxygen Species (ROS to destroy cells. A major problem that arises is determining the ideal time slot to begin treatment after drug application. Our work is meant to show a way to solve this problem by looking at concentration changes of precursors appearing in Heme-Synthesis and using these changes to predict the occurence of PPIX inside the mitochondria. 2000 MSC: 41A05, 41A10, 65D05, 65D17, Keywords: Photodynamic Therapy, Drug light interval, Protoporphyrin IX, Coproporphyrin III, Uroporphyrin III

  1. 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.

  2. Photodynamic action of methylene blue: mutagenesis and synergism

    International Nuclear Information System (INIS)

    Capella, M.A.M.

    1988-01-01

    The associated mutagenesis and the interactions with physical agents in order to potencialize its biological effects are studied. The induction of mutation in bacterias due to photodynamic action of methylene blue is presented as well as the induction of single breaks in bacterial DNA and the relationship between the repair systems, especially the SOS one. The interaction of the photodynamic therapy with low intensity electric current is discussed. (M.A.C.) [pt

  3. Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy

    Science.gov (United States)

    Zhang, Xin; Yan, Qi; Naer Mulatihan, Di; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

    2018-06-01

    The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

  4. 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.

  5. 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.

  6. A placebo-controlled randomized study on the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in fractionated 5-aminolaevulinic acid-photodynamic therapy in patients with psoriasis.

    NARCIS (Netherlands)

    Smits, T.; Kleinpenning, M.M.; Erp, P.E.J. van; Kerkhof, P.C.M. van de; Gerritsen, M.J.P.

    2006-01-01

    BACKGROUND: Topical 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT) for the treatment of psoriasis has been evaluated in a few studies. In these studies different treatment parameters were used, there was a variable clinical response, and a nonhomogeneous fluorescence was seen after

  7. Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes

    NARCIS (Netherlands)

    Broekgaarden, Mans; Weijer, Ruud; Krekorian, Massis; van den IJssel, Bas; Kos, Milan; Alles, Lindy K.; van Wijk, Albert C.; Bikadi, Zsolt; Hazai, Eszter; van Gulik, Thomas M.; Heger, Michal

    2016-01-01

    Photodynamic therapy (PDT) is a tumor treatment modality in which a tumorlocalized photosensitizer is excited with light, which results in local production of reactive oxygen species, destruction of tumor vasculature, tumor hypoxia, tumor cell death, and induction of an anti-tumor immune response.

  8. Smart activatable and traceable dual-prodrug for image-guided combination photodynamic and chemo-therapy.

    Science.gov (United States)

    Hu, Fang; Yuan, Youyong; Mao, Duo; Wu, Wenbo; Liu, Bin

    2017-11-01

    Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 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

  10. 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.

  11. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.

    NARCIS (Netherlands)

    Morton, C.; Horn, M.; Leman, J.; Tack, B.; Bedane, C.; Tjioe, M.; Ibbotson, S.; Khemis, A.; Wolf, P.

    2006-01-01

    OBJECTIVE: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ. DESIGN: Randomized, placebo-controlled study, with follow-up at 3 and

  12. 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)

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. ``Smart'' theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy

    Science.gov (United States)

    Zhang, Yan; Das, Gautom Kumar; Vijayaragavan, Vimalan; Xu, Qing Chi; Padmanabhan, Parasuraman; Bhakoo, Kishore K.; Tamil Selvan, Subramanian; Tan, Timothy Thatt Yang

    2014-10-01

    The current work reports a type of ``smart'' lanthanide-based theranostic nanoprobe, NaDyF4:Yb3+/NaGdF4:Yb3+,Er3+, which is able to circumvent the up-converting poisoning effect of Dy3+ ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.The current work reports a type of ``smart'' lanthanide-based theranostic nanoprobe, NaDyF4:Yb3+/NaGdF4:Yb3+,Er3+, which is able to circumvent the up-converting poisoning effect of Dy3+ ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01717j

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Primary evaluation of a nickel-chlorophyll derivative as a multimodality agent for tumor imaging and photodynamic therapy

    International Nuclear Information System (INIS)

    Ozge Er; Fatma Yurt Lambrecht; Kasim Ocakoglu; Cagla Kayabasi; Cumhur Gunduz

    2015-01-01

    In this study, the biological potential of a nickel chlorophyll derivative (Ni-PH-A) as a multimodal agent for tumor imaging and photodynamic therapy (PDT) was investigated. Optimum conditions of labeling with 131 I were investigated and determined as pH 10 and 1 mg amount of iodogen. Biodistribution results of 131 I labeled Ni-PH-A in female rats indicated that radiolabeled Ni-PH-A maximum uptake in the liver, spleen and ovary was observed at 30 min. Intercellular uptake and PDT efficacy of Ni-PH-A were better in MDAH-2774 (human ovarian endometrioid adenocarcinoma) than in MCF-7 (human breast adenocarcinoma) cells. Ni-PH-A might be a promising multimodal agent for lung, ovary and liver tumor imaging and PDT. (author)

  2. 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.

  3. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  4. 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...

  5. 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.

  6. 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.

  7. Efficiency of photodynamic treatment in patients with early gastric cancer

    Directory of Open Access Journals (Sweden)

    Е. V. Filonenko

    2013-01-01

    Full Text Available The experience of photodynamic therapy for early gastric cancer is described in the article. The treatment results in 68 patients who were excluded for convenient surgical treatment because of advanced age or severe co-morbidity are represented. 63 patients had single tumor, 5 patients – 2 tumors. Four Russian agents: photogem, photosens, radaсhlorin and alasens, were used for photodynamic therapy. The treatment session was performed under local anesthesia during routine endoscopy with diode laser with wavelength consistent with photosensitizer (photogem – 630 nm, photosens – 670 nm, alasens-induced protoporphyrin IX – 635 nm, radaсhlorin – 662 nm. The short-term results were analyzed 1 month after treatment according to endoscopy, morphological study, CT, ultrasound or endosonography. For 73 lesions complete regression was observed in 53 (72.6% and partial regression in 20 tumors (27.4%. The efficacy of photodynamic therapy was shown to be directly associated with tumor size. Thus, for tumors up to 1 cm regression occurred in 100% of cases, up to 1.5 cm – in 70.8%, up to 3 cm – in 65.2%, up to 5 cm – in 58.3%. The median survival rates accounted for 7.31 years, 3-year survival – 83±5%, 5-year - 69±8%. The experience showed that the developed method of photodynamic therapy was promising in treatment for early gastric cancer as an alternative to surgery. 

  8. Phthalocyanine-conjugated upconversion NaYF4:Yb3+/Er3+@SiO2 nanospheres for NIR-triggered photodynamic therapy in a tumor mouse model

    Czech Academy of Sciences Publication Activity Database

    Kostiv, Uliana; Patsula, Vitalii; Noculak, A.; Podhorodecki, A.; Větvička, D.; Poučková, P.; Sedláková, Zdeňka; Horák, Daniel

    2017-01-01

    Roč. 12, Issue 24 (2017), s. 2066-2073 ISSN 1860-7179 R&D Projects: GA ČR(CZ) GA15-01897S Institutional support: RVO:61389013 Keywords : upconversion nanospheres * phthalocyanine * photodynamic therapy Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.225, year: 2016

  9. 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.

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

    Science.gov (United States)

    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.

  11. 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.

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

    Science.gov (United States)

    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.

  13. 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.

  14. Combined photoablative and photodynamic diode laser therapy as an adjunct to non-surgical periodontal treatment: a randomized split-mouth clinical trial.

    Science.gov (United States)

    Giannelli, Marco; Formigli, Lucia; Lorenzini, Luca; Bani, Daniele

    2012-10-01

    Comparing the efficacy of photoablative and photodynamic diode laser in adjunct to scaling -root planing (SRP) and SRP alone for the treatment of chronic periodontitis. Twenty-six patients were studied. Maxillary left or right quadrants were randomly assigned to sham-laser treatment + SRP or laser + SRP. This consisted of photoablative intra/extra-pocket de-epithelization with diode laser (λ = 810 nm), followed by single SRP and multiple photodynamic treatments (once weekly, 4-10 applications, mean ± SD: 3.7 ± 2.4) using diode laser (λ = 635 nm) and 0.3% methylene blue as photosensitizer. The patients were monitored at days 0 and 365 by clinical assessment (probing depth, PD; clinical attachment level, CAL; bleeding on probing, BOP) and at days 0, 15, 30, 45, 60, 75, 90, 365 by cytofluorescence analysis of gingival exfoliative samples taken in proximity of the teeth to be treated (polymorphonuclear leukocytes, PMN; red blood cells, RBC; damaged epithelial cells, DEC; bacteria). At day 365, compared with the control quadrants, the laser + SRP therapy yielded a significant (p Diode laser treatment (photoablation followed by multiple photodynamic cycles) adjunctive to conventional SRP improves healing in chronic periodontitis patients. © 2012 John Wiley & Sons A/S.

  15. Improving cytotoxicity against cancer cells by chemo-photodynamic combined modalities using silver-graphene quantum dots nanocomposites

    Directory of Open Access Journals (Sweden)

    Habiba K

    2015-12-01

    Full Text Available Khaled Habiba,1,2 Joel Encarnacion-Rosado,2,3 Kenny Garcia-Pabon,2,4 Juan C Villalobos-Santos,2,5 Vladimir I Makarov,1 Javier A Avalos,2,6 Brad R Weiner,2,7,8 Gerardo Morell1,2,7 1Department of Physics, University of Puerto Rico – Rio Piedras Campus, 2Molecular Sciences Research Center, University of Puerto Rico, 3Department of Biology, 4Faculty of Education, University of Puerto Rico – Rio Piedras Campus, San Juan, 5Department of Biology, 6Department of Physics, University of Puerto Rico – Bayamon Campus, Bayamon, 7Institute for Functional Nanomaterials, University of Puerto Rico, 8Department of Chemistry, University of Puerto Rico – Rio Piedras Campus, San Juan, PR, USA Abstract: The combination of chemotherapy and photodynamic therapy has emerged as a promising strategy for cancer therapy due to its synergistic effects. In this work, PEGylated silver nanoparticles decorated with graphene quantum dots (Ag-GQDs were tested as a platform to deliver a chemotherapy drug and a photosensitizer, simultaneously, in chemo-photodynamic therapy against HeLa and DU145 cancer cells in vitro. Ag-GQDs have displayed high efficiency in delivering doxorubicin as a model chemotherapy drug to both cancer cells. The Ag-GQDs exhibited a strong antitumor activity by inducing apoptosis in cancer cells without affecting the viability of normal cells. Moreover, the Ag-GQDs exhibited a cytotoxic effect due to the generation of the reactive singlet oxygen upon 425 nm irradiation, indicating their applicability in photodynamic therapy. In comparison with chemo or photodynamic treatment alone, the combined treatment of Ag-GQDs conjugated with doxorubicin under irradiation with a 425 nm lamp significantly increased the death in DU145 and HeLa. This study suggests Ag-GQDs as a multifunctional and efficient therapeutic system for chemo-photodynamic modalities in cancer therapy. Keywords: multifunctional nanoparticles, silver nanoparticles, cancer therapy, drug

  16. Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

    Science.gov (United States)

    Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

    2016-03-31

    There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer. Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated. Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.

  17. 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.

  18. 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.

  19. [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.

  20. 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.

  1. Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in barrett esophagus after endoscopic resection

    NARCIS (Netherlands)

    Peters, F.; Kara, M.; Rosmolen, W.; Aalders, M.; ten Kate, F.; Krishnadath, K.; van Lanschot, J.; Fockens, P.; Bergman, J.

    2005-01-01

    BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or early cancer (HGD/EC) after endoscopic resection in Barrett esophagus. PATIENTS AND METHODS: Study patients were separated into group A,

  2. Enhanced photodynamic efficacy of zinc phthalocyanine by conjugating to heptalysine.

    Science.gov (United States)

    Li, Linsen; Luo, Zhipu; Chen, Zhuo; Chen, Jincan; Zhou, Shanyong; Xu, Peng; Hu, Ping; Wang, Jundong; Chen, Naisheng; Huang, Jinling; Huang, Mingdong

    2012-11-21

    Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of Pc ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)(n) (n = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive in situ method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)(7) has the highest photodynamic efficacy compared to the other conjugates investigated.

  3. 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.

  4. Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances the efficacy of near-infrared targeted photodynamic therapy in esophageal adenocarcinoma cell lines

    NARCIS (Netherlands)

    Hartmans, Elmire; Linssen, Matthijs D.; Sikkens, Claire; Levens, Afra; Witjes, Max J. H.; van Dam, Gooitzen M.; Nagengast, Wouter B.

    2017-01-01

    Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR-tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to selectively treat malignant cells. In this in vitro report we

  5. Photodynamic treatment of Herpes simplex virus infection in vitro

    International Nuclear Information System (INIS)

    Lytle, C.D.; Hester, L.D.

    1976-01-01

    The effects of photodynamic action on in vitro herpes simplex virus infections of CV-1 monkey kidney fibroblasts or human skin fibroblasts were determined using proflavine sulfate and white fluorescent lamps. Photodynamic treatment of confluent cell monolayers prior to virus infection inactivated cell capacity, i.e. the capacity of the treated cells to support subsequent virus growth as measured by plaque formation. The capacity of human cells was more sensitive to inactivation than the capacity of monkey cells when 6 μM proflavine was used. Treated cell monolayers recovered the capacity to support virus plaque formation when virus infection was delayed four days after the treatment. Experiments in which the photodynamically treated monolayers were infected with UV-irradiated virus demonstrated that this treatment induced Weigle reactivation in both types of cells. This reactivation occurred for virus infection just after treatment or 4 days later. A Luria-Latarjet-type experiment was also performed in which cultures infected with unirradiated virus were photodynamically treated at different times after the start of infection. The results showed that for the first several hours of the virus infection the infected cultures were more sensitive to inactivation by photodynamic treatment than cell capacity. By the end of the eclipse period the infected cultures were less sensitive to inactivation than cell capacity. Results from extracellular inactivation of virus growth in monkey cells at 6 μM proflavine indicated that at physiological pH the virus has a sensitivity to photodynamic inactivation similar to that for inactivation of cell capacity. The combined data indicated that photodynamic treatment of the cell before or after virus infection could prevent virus growth. Thus, photodynamic inactivation of infected and uninfected cells may be as important as inactivation of virus particles when considering possible mechanisms in clinical photodynamic therapy for herpes

  6. 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.

  7. 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.

  8. 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.

  9. Experimental photodynamic therapy with MESO-tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Nekvasil, Miloš; Škobisová, Eva; Urbánková, Eva; Jirsa, M.; Zadinová, M.; Poučková, P.; Klepáček, I.

    2003-01-01

    Roč. 103, č. 5 (2003), s. 693-702 ISSN 0020-7136 R&D Projects: GA MZd NC4810; GA MZd NC6564 Institutional research plan: CEZ:AV0Z5011922 Keywords : photodynamic therapy of tumors * meso-tetrakis-phenylporphyrin * liposomal drug delivery Subject RIV: FD - Oncology ; Hematology Impact factor: 4.375, year: 2003

  10. 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. 

  11. Pulse photodynamic therapy reduces inflammation without compromising efficacy in the treatment of multiple mild actinic keratoses of the face and scalp

    DEFF Research Database (Denmark)

    Wiegell, S R; Petersen, Bibi Øager; Wulf, H C

    2016-01-01

    BACKGROUND: The main side-effects of photodynamic therapy (PDT) for actinic keratoses (AKs) are post-treatment erythema and oedema, and pain during illumination. Severe erythema after PDT enhances the down time associated with the treatment. OBJECTIVES: To evaluate in a randomized intraindividual...... on the face and scalp. The use of a short MAL application time and topical corticosteroid did not affect the efficacy of PDT and may be an easy way to make PDT treatment of large visible areas more acceptable.......BACKGROUND: The main side-effects of photodynamic therapy (PDT) for actinic keratoses (AKs) are post-treatment erythema and oedema, and pain during illumination. Severe erythema after PDT enhances the down time associated with the treatment. OBJECTIVES: To evaluate in a randomized intraindividual...... study whether pulse-PDT and corticosteroid pulse-PDT would reduce treatment-induced erythema compared with conventional PDT. METHODS: Twenty-two patients with multiple mild AKs on the face and scalp were treated with methyl aminolaevulinate (MAL)-PDT in three similar areas. Two areas were incubated...

  12. 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.

  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. Near infrared imaging-guided photodynamic therapy under an extremely low energy of light by galactose targeted amphiphilic polypeptide micelle encapsulating BODIPY-Br2.

    Science.gov (United States)

    Liu, Le; Ruan, Zheng; Li, Tuanwei; Yuan, Pan; Yan, Lifeng

    2016-10-18

    Near infrared (NIR) imaging-guided photodynamic therapy (PDT) is attractive, especially the utilization of one dye as both a photosensitizer and fluorescent probe, and the as-synthesized BODIPY-Br 2 molecule is a candidate. Here, a galactose targeted amphiphilic copolymer of a polypeptide was synthesized and its micelles work as nanocarriers for BODIPY for targeting the NIR imaging-guided PDT of hepatoma cancer cells. At the same time, BODIPY could light up the cytoplasm for real-time imaging and kill cancer cells when the light was switched on. In vitro tests performed on both HepG2 and HeLa cells confirmed that the as-prepared PMAGP-POEGMA-PLys-B micelles showed efficient cell suppression of the cells with galactose receptors in the presence of light under an extremely low energy density (6.5 J cm -2 ). This protocol highlights the potential of polypeptides as biodegradable carriers for NIR image-guided and confined targeting photodynamic therapy.

  15. Substrate mediated enzyme prodrug therapy

    DEFF Research Database (Denmark)

    Fejerskov, Betina; Jarlstad Olesen, Morten T; Zelikin, Alexander N

    2017-01-01

    Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administra......Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug...

  16. Potentiation of the photodynamic action of hypericin.

    Science.gov (United States)

    Saw, Constance Lay Lay; Heng, Paul Wan Sia; Olivo, Malini

    2008-01-01

    Hypericin (HY) is an interesting photosensitizer with dark activity and photodynamic therapy (PDT) effects via p53-independent pathway. In photodynamic diagnosis (PDD) of bladder cancer using HY, very high sensitivity and specificity were reported, in comparison with its counterpart, 5-aminolevulinic acid (5-ALA). HY was tested for the detection of human gastric cancer. It was also studied for treating some cancers and age-related macular degeneration and showed some promising findings. Several strategies to enhance the efficacy of HY-PDD and HY-PDT are reviewed. Using fractionated light dosing, fractionated drug dosing, hyperthermia, adjuvants such as oxygen carrier/antiangiogenesis, chemical modifications, and formulation approaches to enhance the PDT effects of HY are topics of this review. Despite cutting-edge technology approach such as preparing transferring-mediated targeting HY liposomes and nanoparticles of HY, such preparations did not always offer the desired enhanced treatment effects. It turns out that simple solutions of HY, especially those prepared without using plasma protein, were more successful in enhancing the delivery of HY for in vitro and in vivo systems. Thus, the HY-PDT with these formulations performed better. It is anticipated that HY-PDD and HY-PDT can be enhanced and optimized with the right combination of light dosimetry and drug dose in an effective formulation containing a suitable adjuvant. Hyperoxygenation and hyperthermia can also be used to further enhance the efficacy of HY-PDT.

  17. 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.

  18. 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.

  19. 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)

  20. 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

  1. Killing Effect of Ad5/F35-APE1 siRNA Recombinant Adenovirus in Combination with Hematoporphrphyrin Derivative-Mediated Photodynamic Therapy on Human Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lei Xia

    2013-01-01

    Full Text Available The main goal of this work is to investigate the killing effects and molecular mechanism of photodynamic therapy (PDT mediated by the Ad5/F35-APE1 siRNA recombinant adenovirus in combination with a hematoporphrphyrin derivative (HpD in the A549 human lung adenocarcinoma cell line in vitro to provide a theoretical reference for treating lung cancer by HpD-PDT. By using the technologies of MTT, flow cytometry, ELISA, and western blot, we observed that the proliferation inhibition and apoptosis of the A549 cells were significantly higher than the control group ( after HpD-PDT was performed. The inhibitory efficiency is dependent on the HpD concentration and laser intensity dose. The inhibitory effect on the proliferation of A549 cells of Ad5/F35-APE1 siRNA is more significant after combining with PDT, as indicated by a significant elevation of the intracellular ROS level and the expression of inflammatory factors (. The HpD-PDT-induced expression of the APE1 protein reached the peak after 24 h in A549 cells. The inhibition of APE1 expression in A549 cells was most significant after 48 hours of infection by Ad5/F35-APE1 siRNA recombinant adenovirus (10 MOI. In conclusion, the Ad5/F35-APE1 siRNA recombinant adenovirus could efficiently inhibit the HpD-PDT-induced APE1 expression hence could significantly enhance the killing effect of HpD-PDT in lung cancer cells.

  2. 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. 

  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. Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells

    Czech Academy of Sciences Publication Activity Database

    Kleban, J.; Mikeš, J.; Szilárdiová, B.; Koval, J.; Sačková, V.; Solár, P.; Horváth, Viktor; Hofmanová, Jiřina; Kozubík, Alois; Fedoročko, P.

    2007-01-01

    Roč. 83, č. 5 (2007), s. 1174-1185 ISSN 0031-8655 R&D Projects: GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hypericin * photodynamic therapy * arachidonic acid inhibitors Subject RIV: BO - Biophysics Impact factor: 2.172, year: 2007

  5. 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)

  6. Preparation of a chlorophyll derivative and investigation of its photodynamic activities against cholangiocarcinoma.

    Science.gov (United States)

    Wu, Zhong-Ming; Wang, Li; Zhu, Wei; Gao, Ying-Hua; Wu, Hai-Ming; Wang, Mi; Hu, Tai-Shan; Yan, Yi-Jia; Chen, Zhi-Long

    2017-08-01

    Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma. Published by Elsevier Masson SAS.

  7. 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)

  8. 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.

  9. 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

  10. Hemoporfin Photodynamic Therapy for Port-Wine Stain: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    Full Text Available Photodynamic therapy (PDT has shown potentially beneficial results in treating port-wine stain, but its benefit-risk profile remains undefined. This study aimed to evaluate the efficacy and safety of PDT conducted with hemoporfin and a 532 nm continuous wave laser to treat port-wine stain clinically.This randomized clinical trial was conducted in eight hospitals in China. Participants were adolescent and adult patients (age range: 14-65 years old with port-wine stain. During stage 1 (day 1 to week 8 all patients were randomized at a 3:1 ratio to treatment (532 nm laser irradiation (96-120 J/cm2 with hemoporfin (5mg/kg; PDT-hemoporfin, n = 330 or placebo groups (irradiation with placebo (PDT-placebo, n = 110; during stage 2 (week 8 to 16 patients in both groups were offered treatment. Clinician-evaluators, who were blind to the study, classified each case on the following four-level scale according to assessment of before and after standardized pictures of the lesion area: no improvement: <20%; some improvement: 20-59%; great improvement: 60-89%; or nearly completely resolved: ≥90%. The primary efficacy endpoint was proportion of patients achieving at least some improvement at week 8. The secondary efficacy endpoints were proportion of patients achieving nearly completely resolved or at least great improvement at week 8, proportion of patients achieving early completely resolved, at least great improvement, or at least some improvement at week 16, and the corresponding satisfaction of the investigators and the patients (designated as 'excellent', 'good', 'moderate', or 'ineffective' at weeks 8 and 16.Compared to the PDT-placebo group, the PDT-hemoporfin group showed a significantly higher proportion of patients that achieved at least some improvement (89.7% [n = 295; 95% CI, 85.9%-92.5%] vs. 24.5% [n = 27; 95% CI, 17.4%-33.3%] at week 8 (P < 0.0001 and higher improvements for all secondary efficacy endpoints. Treatment reactions occurred in 99

  11. 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.

  12. 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

  13. 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.

  14. A randomized comparative study of the safety and efficacy of photodynamic therapy using Photofrin II combined with palliative radiotherapy versus palliative radiotherapy alone in patients with inoperable obstructive non-small cell bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Lam, S.; Kostashuk, E.C.; Coy, E.P.; Laukkanen, E.; LeRiche, J.C.; Mueller, H.A.; Szasz, I.J.

    1987-01-01

    Preliminary results suggest that 3000 cGy radiation therapy alone offers only transient palliation for patients with obstructive endobronchial tumor. The addition of photodynamic therapy (PDT) prior to XRT provides significantly better and longer lasting local control. The combined treatment may also improve survival. It is possible that a therapeutic dose-6000 cGy radiation therapy may offer better local control than 3000 cGy. (author)

  15. 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.

  16. Induction of immunological changes induced by photodynamic therapy (PDT) for cancer

    International Nuclear Information System (INIS)

    Reginato, E.

    2014-01-01

    Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and certain non-malignant diseases. PDT consists of systemic or topical administration of a photosensitizer (PS) or a PS precursor (prodrug) such as aminolevulinic acid, followed by irradiation of the diseased area with light of wavelengths corresponding to the absorbance band of the PS. When the PS is activated to its excited state by the light, it can react with the surrounding environment and transfer energy to the molecular tissue oxygen, triggering a photochemical reaction and causing cell death. Besides causing direct cytotoxic effects on illuminated cancer cells, PDT is known to cause damage to the tumor vasculature and to induce the release of pro-inflammatory mediators. Previous studies in mouse models and patients have demonstrated that PDT is capable of affecting both innate and adaptive arms of the immune system. It has been shown that besides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT can lead to development of anti-tumor memory immunity that potentially prevents the recurrence of cancer. Moreover, several lines of evidence suggest that PDT may also interfere with the immune-suppressive regulatory T cells (Treg). In the present work we thoroughly investigated the intricate immune profile of PDT in both preclinical and clinical studies, involving (1) a colon adenocarcinoma CT26 wild-type tumor mouse model, (2) patients suffering from esophageal squamous cell carcinoma (ESCC) treated with porfimer sodium (Photofrin) and Laser and (3) patients with actinic keratoses (AK), treated with the porphyrin precursor methyl aminolevulinate and red LED light. Our results from the animal model suggested that PDT did not cause any long-term effect on the levels of Treg in the spleen or lymph nodes. However, Treg cells depletion via administration of cyclophosphamide (CY) prior PDT potentiated anti-tumor immunity, leading to

  17. Photodynamic therapy using a novel irradiation source, LED lamp, is similarly effective to photodynamic therapy using diode laser or metal-halide lamp on DMBA- and TPA-induced mouse skin papillomas.

    Science.gov (United States)

    Takahashi, Hidetoshi; Nakajima, Susumu; Ogasawara, Koji; Asano, Ryuji; Nakae, Yoshinori; Sakata, Isao; Iizuka, Hajime

    2014-08-01

    Photodynamic therapy (PDT) is useful for superficial skin tumors such as actinic keratosis and Bowen disease. Although PDT is non-surgical and easily-performed treatment modality, irradiation apparatus is large and expensive. Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-ο-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model, we compared the efficacy of TONS501- and ALA-PDT with a LED lamp, a diode laser lamp or a metal-halide lamp on the skin tumor regression. TONS501-PDT using 660 nm LED lamp showed anti-tumor effect at 1 day following the irradiation and the maximal anti-tumor effect was observed at 3 days following the irradiation. There was no significant difference in the anti-tumor effects among TONS501-PDT using LED, TONS501-PDT using diode laser, and 5-aminolevulinic acid hydrochloride (ALA)-PDT using metal-halide lamp. Potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma was observed by TONS501-PDT using 660 nm LED, which might be more useful for clinical applications. © 2014 Japanese Dermatological Association.

  18. Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell line

    International Nuclear Information System (INIS)

    Yamada, Hiroko; Arai, Toshiyuki; Endo, Nobuyuki; Yamashita, Kouhei; Nonogawa, Mitsuru; Makino, Keisuke; Fukuda, Kazuhiko; Sasada, Masataka; Uchiyama, Takashi

    2005-01-01

    6-Formylpterin (6FP) has the potential to produce singlet oxygen ( 1 O 2 ) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the 1 O 2 generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate 1 O 2 to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable pterin derivatives has the potential for application in PDT

  19. Changes in visual function and thickness of macula after photodynamic therapy for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Kyoko Okada

    2009-09-01

    Full Text Available Kyoko Okada, Mariko Kubota-Taniai, Masayasu Kitahashi, Takayuki Baba, Yoshinori Mitamura, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To determine the correlation between the changes in the central retinal sensitivity and the changes in the foveal thickness (FT after photodynamic therapy (PDT for age-related macular degeneration (AMD.Methods: Nineteen eyes of 19 patients with choroidal neovasularizations (CNVs secondary to AMD were studied. The pretreatment values of the central retinal sensitivity determined by Micro Perimeter 1 (MP1; Nidek Technologies, best-corrected visual acuity (BCVA, and optical coherence tomography (OCT-determined FT were compared to the postoperative values at three and six months after PDT.Results: At six months, the retinal sensitivity within the central 10° was significantly improved (P = 0.02 and the FT was significantly thinner (P = 0.016. The BCVA, however, did not change significantly (P = 0.80. The changes in the retinal sensitivities were significantly correlated with the changes in the decrease in the FT (r = -0.59, P = 0.012 within the central 10° at six months after PDT.Conclusion: Significant improvements in retinal sensitivities within the central 10° and a decrease in FT were observed even though the BCVA was not significantly improved. The measurement of retinal sensitivity by MP1 may be a better method to assess central visual function than the conventional visual acuity after PDT.Keywords: age-related macular degeneration, fundus-related microperimetry, optical coherence tomography, photodynamic therapy

  20. 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.

  1. 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...

  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. 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.

  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. 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

  6. Enhanced cellular uptake and phototoxicity of Verteporfin-conjugated gold nanoparticles as theranostic nanocarriers for targeted photodynamic therapy and imaging of cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Linlin [Tianjin Key Laboratory for Photoelectric Materials and Devices, School of Materials Science & Engineering, Tianjin University of Technology, Tianjin 300384 (China); Graduate School of Energy Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Tae-Hyun; Kim, Hae-Won [Department of Nanobiomedical Science, Dankook University Graduate School, Cheonan 330-714 (Korea, Republic of); Institute of Tissue Regeneration Engineering (ITREN) & College of Dentistry, Dankook University, Cheonan 330-714 (Korea, Republic of); Ahn, Jin-Chul [Department of Biomedical Science, College of Medicine, Dankook University, Cheonan, 330-714 (Korea, Republic of); Kim, So Yeon, E-mail: kimsy@cnu.ac.kr [Graduate School of Energy Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Department of Chemical Engineering Education, College of Education, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2016-10-01

    Activatable theranostics with the capacity to respond to a given stimulus have recently been intensively explored to develop more specific, individualized therapies for various diseases, and to combine diagnostic and therapeutic capabilities into a single agent. In this work, we designed tumor-targeting ligand-conjugated block copolymer-gold nanoparticle (AuNP) conjugates as multifunctional nanocarriers of the hydrophobic photosensitizer (PS), verteporfin (Verte), for simultaneous photodynamic therapy and imaging of cancers. Folic acid (FA)-conjugated block copolymers composed of polyethylene glycol (PEG) and poly-β-benzyl-L-aspartate (PBLA) were attached to citrate-stabilized AuNPs through a bidentate dihydrolipoic acid (DHLA) linker. The resulting AuNP conjugates (FA-PEG-P(Asp-Hyd)-DHLA-AuNPs) were significantly more stable than unmodified AuNPs, and their optical properties were not affected by pH. The hydrophobic PS, Verte, was covalently incorporated onto the surfaces of the AuNP conjugates through a pH-sensitive linkage, which increased the water solubility of Verte from < 1 μg/ml to > 2000 μg/ml. The size of FA-PEG-P(Asp-Hyd)-DHLA-AuNPs-Verte as determined by light-scattering measurements was about 110.3 nm, and FE-SEM and FE-TEM images showed that these nanoparticles were spherical and showed adequate dispersivity after modification. In particular, an in vitro cell study revealed high intracellular uptake of FA-PEG-P(Asp-Hyd)-DHLA-AuNPs-Verte (about 98.62%) and marked phototoxicity after laser irradiation compared with free Verte. These results suggest that FA-PEG-P(Asp-Hyd)-DHLA-AuNPs-Verte has great potential as an effective nanocarrier for dual imaging and photodynamic therapy. - Highlights: • We designed theranostic nanocarriers for photodynamic therapy and imaging of cancers. • AuNP conjugates had a spherical shape and a narrow size distribution with a mean diameter of 110.3 nm. • Cellular uptake of free Verte was 18.86%, whereas that of Au

  7. "Smart" theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy.

    Science.gov (United States)

    Zhang, Yan; Das, Gautom Kumar; Vijayaragavan, Vimalan; Xu, Qing Chi; Padmanabhan, Parasuraman; Bhakoo, Kishore K; Selvan, Subramanian Tamil; Tan, Timothy Thatt Yang

    2014-11-07

    The current work reports a type of "smart" lanthanide-based theranostic nanoprobe, NaDyF4:Yb(3+)/NaGdF4:Yb(3+),Er(3+), which is able to circumvent the up-converting poisoning effect of Dy(3+) ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.

  8. 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)

  9. 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)

  10. A supramolecular photosensitizer system based on the host-guest complexation between water-soluble pillar[6]arene and methylene blue for durable photodynamic therapy.

    Science.gov (United States)

    Yang, Kui; Wen, Jia; Chao, Shuang; Liu, Jing; Yang, Ke; Pei, Yuxin; Pei, Zhichao

    2018-06-05

    A supramolecular photosensitizer system WP6-MB was synthesized based on water-soluble pillar[6]arene and the photosensitizer methylene blue (MB) via host-guest interaction. MB can complex with WP6 directly with a high complex constant without further modification. In particular, WP6-MB can reduce the dark toxicity of MB remarkably. Furthermore, it can efficiently overcome photobleaching and extend the time for singlet oxygen production of MB upon light irradiation, which is significant for durable photodynamic therapy.

  11. 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.

  12. 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.

  13. 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.

  14. Topical photodynamic therapy with porphyrin precursors--assessment of treatment-associated pain in a retrospective study.

    Science.gov (United States)

    Steinbauer, Julia Maria; Schreml, Stephan; Babilas, Philipp; Zeman, Florian; Karrer, Sigrid; Landthaler, Michael; Szeimies, Rolf-Markus

    2009-08-01

    Photodynamic therapy (PDT) with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is an approved modality for the non-invasive treatment of actinic keratoses (AK) and basal cell carcinoma (BCC) offering excellent cosmetic outcome. However, pain during and after illumination is the most frequent and limiting side effect. The aim of this study was to precisely assess how reported pain during PDT is influenced by sex, age, treatment site, disease (AK/BCC) as well as the photosensitizer used. 467 lesions consisting of AK (primary treatments: n=158; follow-up: n=47) or BCC (primary treatments: n=138; follow-up: 124) were treated by ALA- or MAL-PDT using metal halide lamps (580-750 nm). Pain was assessed during illumination using a continuous visual analogue scale (VAS). Factors predictive for higher pain levels during PDT are treatment of the head, treating AK and using ALA. The observed results may improve patient management and predict which level of pain to expect, and what kind of pain relief to prepare.

  15. 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.

  16. 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.

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

    Science.gov (United States)

    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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Efficiency of photodynamic therapy in the treatment of peri-implantitis: A three-month randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Rakašević Dragana

    2016-01-01

    Full Text Available Introduction. Peri-implantitis is an inflammatory lesion of peri-implant tissues. Eradication of the causative bacteria and decontamination of the implant surface is essential in achieving predictable and stabile clinical results. Photodynamic therapy (PDT is non-invasive adjuvant therapeutic method to surgery in the treatment of bacterial infection. Objective. The aim of this study was to evaluate early clinical and microbiological outcomes of periimplantitis after surgical therapy with adjuvant PDT. Methods. Fifty-two diagnosed peri-implantitis sites were divided into two groups. PDT was used for decontamination of implant surface in the study group; in the control group, chlorhexidine gel (CHX followed by saline irrigation was applied. Several clinical parameters were recorded before the treatment (baseline values and three months after surgical treatment. Samples for microbiological identification were collected before therapy, during the surgical therapy (before and after decontamination of implant surface, and three months thereafter, and analyzed with identification systems using biochemical analysis. Results. The use of PDT resulted in significant decrease of bleeding on probing in comparison to CHX (p < 0.001. It showed significant decontamination of implant surfaces with complete elimination of anaerobic bacteria immediately after surgical procedure and three months later. Conclusion. The results indicate that PDT can be used as an adjuvant therapy to surgery for decontamination of implant surface and surrounding peri-implant tissues within the treatment of peri-implantitis. [Projekat Ministarstva nauke Republike Srbije, br. 41008

  6. Treating Melanoma Metastases with a Novel Photodynamic Approach

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0270 TITLE: Treating Melanoma Metastases with a Novel Photodynamic Approach PRINCIPAL INVESTIGATOR: Jin Xie...Metastases with a Novel Photodynamic Approach 5a. CONTRACT NUMBER Treating Melanoma Metastases with a Novel Photodynamic Approach 5b. GRANT NUMBER...ligand and after systemic injection, home to tumors in the lung. X-ray of relatively low doses can then be applied externally to the lung area to

  7. Photodynamic treatment of a secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher syndrome type I.

    Science.gov (United States)

    Osman, Saatci A; Aylin, Yaman; Arikan, Gul; Celikel, Harika

    2007-03-01

    Vasoproliferative tumours may be primary or secondary and present with severe exudation leading to marked visual loss. We describe a 47-year-old man with unilateral secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher I syndrome who was successfully treated with a single session of photodynamic treatment. Standard treatment protocol was used except that the treatment duration was doubled. A year after the treatment, the angioma-like tumour vanished and exudation was dramatically reduced. Photodynamic therapy seems to be a minimally invasive and safe technique in eyes with secondary vasoproliferative tumours.

  8. Photomedicine and Stem Cells; The Janus face of photodynamic therapy (PDT) to kill cancer stem cells, and photobiomodulation (PBM) to stimulate normal stem cells

    Science.gov (United States)

    Abrahamse, Heidi; Hamblin, Michael R.

    2017-12-01

    Janus, the ancient Roman god depicted with two faces is an appropriate metaphor for light therapy. In the right photodynamic therapy conditions, light is able to kill nearly anything that is living such as cancers, microorganisms, parasites, and more. On the opposite face, light of the correct wavelength and proper dose (photobiomodulation) can heal, regenerate, protect, revitalize and restore any kind of dead, damaged, stressed, dying, degenerating cells, tissue, or organ system. This book discusses both sides of Janus' face in regards to light therapy.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Evaluation of efficacy of photodynamic therapy as an adjunct to nonsurgical periodontal therapy in treatment of chronic periodontitis patients: A clinico-microbiological study.

    Science.gov (United States)

    Raj, K Ravi; Musalaiah, Svvs; Nagasri, M; Kumar, P Aravind; Reddy, P Indeevar; Greeshma, M

    2016-01-01

    Photodynamic therapy (PDT) is a local noninvasive treatment modality without side effects caused by antibiotics. The aim of this study was to evaluate the efficacy of adjunctive use of PDT with scaling and root planing as compared with SRP alone in the treatment of chronic periodontitis. Twenty participants with chronic periodontitis having probing pocket depths (PDs) of ≥5 mm were selected for the study. Patients were randomly divided into control group and test group with ten patients in each group. Full-mouth SRP was performed in both the groups, followed by PDT in test group. Assessment of plaque index (PI), gingival index (GI), PD, and clinical attachment level (CAL) was done at baseline and after 3 months. Microbiological assessment of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola was done by polymerase chain reaction (PCR) at baseline and 3 months after the therapy. There was a significant reduction in PI, GI, PD, CAL, and microbiologic parameters in test group, following SRP and PDT, when compared with SRP alone in control group. PDT in conjunction with SRP has shown additional improvement in periodontal parameters when compared to SRP alone and has a beneficial effect in chronic periodontitis patients.

  16. 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.

  17. X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield

    OpenAIRE

    Clement, Sandhya; Deng, Wei; Camilleri, Elizabeth; Wilson, Brian C.; Goldys, Ewa M.

    2016-01-01

    Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF3 nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8?keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79???0.05 for the conjugate with 31 verteporfin molecules per CeF3 nanoparticle, the highest conjugation level used. From this result ...

  18. 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)

  19. 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)

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Terapia fotodinâmica: revisão da literatura e documentação iconográfica Photodynamic therapy: a review of the literature and image documentation

    Directory of Open Access Journals (Sweden)

    Maria Cláudia Almeida Issa

    2010-08-01

    Full Text Available A terapia fotodinâmica é uma reação química ativada por luz usada para destruição seletiva de um tecido e requer um agente fotossensibilizante no tecido-alvo, uma fonte de luz e oxigênio. Estão disponíveis, no momento, o ácido 5-aminolevulínico para tratamento de ceratoses actínicas e o metilaminolevulinato, aprovado para tratamento de ceratoses actínicas, carcinoma basocelular e doença de Bowen. As fontes de luz utilizadas para a terapia fotodinâmica devem emitir comprimentos de onda no espectro de absorção do fotossensibilizante escolhido. As lâmpadas LED (light emitting diode são as indicadas para terapia fotodinâmica tópica no tratamento do câncer de pele não melanoma. A terapia fotodinâmica deve ser considerada, em particular, para pacientes que apresentam lesões superficiais, múltiplas, disseminadas e para pacientes imunossuprimidos. Mais recentemente, a terapia fotodinâmica tem sido indicada no tratamento do fotoenvelhecimento, acne, hidrosadenite, esclerodermia, psoríase, verrugas, leishmaniose, entre outras. Por este trabalho será possível ter acesso a uma extensa revisão da literatura sobre terapia fotodinâmica, seus mecanismos, indicações e resultados, seguida de comentários e críticas pertinentes ao assunto.Photodynamic therapy (PDT consists of a chemical reaction activated by light energy that is used to selectively destroy tissue. The reaction requires a photosensitizer in the target tissue, a light source and oxygen. The most extensively studied photosensitizing agents for PDT are 5-aminolevulinic acid for the treatment of actinic keratosis and methyl-aminolevulinate, which has been approved for the treatment of actinic keratosis, basal cell carcinoma and Bowen's disease. The light sources used in photodynamic therapy should emit light at wavelengths within the absorption spectrum of the photosensitizer used in PDT treatment. Light emitting diode (LED lamps are indicated for the photodynamic

  6. 5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

    Directory of Open Access Journals (Sweden)

    Qing-Zhao Zhang

    Full Text Available Staphylococcus aureus (S. aureus is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT, which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA, a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

  7. 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

  8. 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)

  9. 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.

  10. 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.

  11. 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)

  12. 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.

  13. Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.

    Science.gov (United States)

    Anderson, Catriona M H; Jevons, Mark; Thangaraju, Muthusamy; Edwards, Noel; Conlon, Nichola J; Woods, Steven; Ganapathy, Vadivel; Thwaites, David T

    2010-01-01

    5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy, fluorescent diagnosis, and fluorescent-guided resection because it leads to accumulation of the photosensitizer protoporphyrin IX (PpIX) in tumor tissues. ALA has good oral bioavailability, but high oral doses are required to obtain selective PpIX accumulation in colonic tumors because accumulation is also observed in normal gut mucosa. Structural similarities between ALA and GABA led us to test the hypothesis that the H(+)-coupled amino acid transporter PAT1 (SLC36A1) will contribute to luminal ALA uptake. Radiolabel uptake and electrophysiological measurements identified PAT1-mediated H(+)-coupled ALA symport after heterologous expression in Xenopus oocytes. The selectivity of the nontransported inhibitors 5-hydroxytryptophan and 4-aminomethylbenzoic acid for, respectively, PAT1 and the H(+)-coupled di/tripeptide transporter PepT1 (SLC15A1) were examined. 5-Hydroxytryptophan selectively inhibited PAT1-mediated amino acid uptake across the brush-border membrane of the human intestinal (Caco-2) epithelium whereas 4-aminomethylbenzoic acid selectively inhibited PepT1-mediated dipeptide uptake. The inhibitory effects of 5-hydroxytryptophan and 4-aminomethylbenzoic acid were additive, demonstrating that both PAT1 and PepT1 contribute to intestinal transport of ALA. This is the first demonstration of overlap in substrate specificity between these distinct transporters for amino acids and dipeptides. PAT1 and PepT1 expression was monitored by reverse transcriptase-polymerase chain reaction using paired samples of normal and cancer tissue from human colon. mRNA for both transporters was detected. PepT1 mRNA was increased 2.3-fold in cancer tissues. Thus, increased PepT1 expression in colonic cancer could contribute to the increased PpIX accumulation observed. Selective inhibition of PAT1 could enhance PpIX loading in tumor tissue relative to that in normal tissue.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Carbon nanotubes as cancer therapeutic carriers and mediators

    Science.gov (United States)

    Son, Kuk Hui; Hong, Jeong Hee; Lee, Jin Woo

    2016-01-01

    Carbon nanotubes (CNTs) have received increasing attention in biomedical fields because of their unique structures and properties, including high aspect ratios, large surface areas, rich surface chemical functionalities, and size stability on the nanoscale. Particularly, they are attractive as carriers and mediators for cancer therapy. Through appropriate functionalization, CNTs have been used as nanocarriers for anticancer drugs including doxorubicin, camptothecin, carboplatin, cisplatin, paclitaxel, Pt(II), and Pt(IV), and genes including plasmid DNA, small-interfering RNA, oligonucleotides, and RNA/DNA aptamers. CNTs can also deliver proteins and immunotherapy components. Using combinations of light energy, they have also been applied as mediators for photothermal therapy and photodynamic therapy to directly destroy cancer cells without severely damaging normal tissue. If limitations such as a long-term cytotoxicity in the body, lack of size uniformity during the synthetic process, loading deviations for drug–CNT complexes, and release controllability at the target point are overcome, CNTs will become one of the strongest tools that are available for various other biomedical fields as well as for cancer therapy. PMID:27785021

  19. Terapia fotodinâmica em dermatologia: princípios básicos e aplicações Photodynamic therapy in dermatology: basic principles

    Directory of Open Access Journals (Sweden)

    Luís Torezan

    2009-10-01

    Full Text Available A terapia fotodinâmica envolve a administração de uma droga fotossensibilizante e sua ativação subsequente pela luz de comprimento de onda correspondente ao espectro de absorção do fotossensibilizador. Atualmente, a terapia fotodinâmica tópica é aprovada para o tratamento de condições oncológicas cutâneas como queratoses actínicas, doença de Bowen e carcinoma basocelular superficial em diversos países do mundo. Estudos multicêntricos controlados e randomizados demonstram a alta eficácia e resultado cosmético final superior dessa modalidade terapêutica em relação aos tratamentos convencionais. Para condições cutâneas não oncológicas, como acne vulgar, verrugas virais e esclerodermia localizada, há também relatos e série de casos confirmando o potencial terapêutico da terapia fotodinâmica. O desenvolvimento de fotossensibilizantes tópicos, ácido 5-aminolevulínico (ALA ou seu metiléster (MAL, frente aos derivados da hematoporfirina de aplicação sistêmica, permitiu um grande avanço na popularidade da TFD na dermatologia, uma vez que tanto ALA quanto MAL tópicos não induzem mais fotossensibilidade generalizada prolongada. A produção de intermediários reativos de oxigênio, como oxigênio singlet, depende da concentração, da localização do fotossensibilizante no tecido alvo, assim como da dose de luz utilizada. Tanto as lâmpadas de amplo espectro quanto os LEDs (do inglês light emitting diodes constituem fontes de luz adequadas para que os efeitos citotóxicos da terapia fotodinâmica resultem na destruição do tumor ou seus efeitos imunomodulatórios atuem melhorando as condições inflamatórias cutâneas.Photodynamic therapy involves the administration of a photosensitizing drug and its subsequent activation by light at wavelengths matching the absorption spectrum of the photosensitizer. Currently, topical photodynamic therapy has received approval for the treatment of cutaneous oncologic

  20. Progress toward development of photodynamic vaccination against infectious/malignant diseases and photodynamic mosquitocides

    Science.gov (United States)

    Chang, Kwang Poo; Kolli, Bala K.; Fan, Chia-Kwung; Ng, Dennis K. P.; Wong, Clarence T. T.; Manna, Laura; Corso, Raffaele; Shih, Neng-Yao; Elliott, Robert; Jiang, X. P.; Shiao, Shin-Hong; Fu, Guo-Liang

    2018-02-01

    Photodynamic therapy (PDT) uses photosensitizers (PS) that are excited with light to generate ROS in the presence of oxygen for treating various diseases. PS also has the potential use as photodynamic insecticides (PDI) and for light-inactivation of Leishmania for photodynamic vaccination (PDV). PDT-inactivated Leishmania are non-viable, but remain immunologically competent as whole-cell vaccines against leishmaniasis, and as a universal carrier for delivery of add-on vaccines against other infectious and malignant diseases. We have screened novel PS, including Zn- and Si-phthalocyanines (PC) for differential PDT activities against Leishmania, insect and mammalian cells in vitro to assess their PDI and PDV potential. Here, Zn-PC were conjugated with various functional groups. The conjugates were examined for uptake by cells as a prerequisite for their susceptibility to light-inactivation. PDT sensitivity was found to vary with cell types and PS used. PDI potential of several PS was demonstrated by their mosquito larvicidal PDT activities in vitro. PDT-inactivated Leishmania were stored frozen for PDV in several ongoing studies: [1] Open label trial with 20 sick dogs for immunotherapy of canine leishmaniasis after chemotherapy in Naples, Italy. Clinical follow-up for >3 years indicate that the PDV prolongs their survival; [2] PDV of murine models with a human lung cancer vaccine showed dramatic tumor suppression; [3] Open label trial of multiple PDV via compassionate access to 4 advanced cancer patients showed no clinically adverse effects. Two subjects remain alive. Genetic modifications of Leishmania are underway to further enhance their safety and efficacy for PDV by installation of activable mechanisms for self-destruction and spontaneous light-emission.

  1. 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.

  2. 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)

  3. The effect of photodynamic therapy on pathogenic bacteria around peri-implant sulcus and in the cavity between abutment and implant after healing phase: A prospective clinical study.

    Science.gov (United States)

    Zhou, Lin-Yi; Shi, Jun-Yu; Zhu, Yu; Qian, Shu-Jiao; Lai, Hong-Chang; Gu, Ying-Xin

    2018-05-14

    To compare levels of pathogens from peri-implant sulcus versus abutment screw cavities after photodynamic therapy. Twenty patients were included. Photodynamic therapy (PDT) was applied both in sulcus and cavities after sampling following suprastructures loading, and repeated after 2 weeks. Two samples each containing four paper points were collected for each implant at baseline, 2 weeks, 3 months: (i) peri-implant sulcus and (ii) abutment screw cavities. Seventy-five percent ethanol was applied in another 20 patients as the control group in the same way. qPCR was used to quantify periodontal pathogens: Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans. PDT showed a better bacterial reduction than ethanol. P. g. and F. n. were most frequently detected, while less for S. m. P. gingivalis' proportion from both sites was significantly higher than the other two bacteria (P abutment screw cavities were always less than those from peri-implant sulcus and was significantly lower for total bacteria at 3 months (P abutment screw cavities significantly reduced at 3 months compared to baseline (P abutment screw cavities in the long run, suggesting PDT an effective way sterilizing inner surface of oral implant suprastrutures. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  4. Randomized comparative study of the safety and efficacy of photodynamic therapy using Photofrin II combined with palliative radiotherapy versus palliative radiotherapy alone in patients with inoperable obstructive non-small cell bronchogenic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lam, S.; Kostashuk, E.C.; Coy, E.P.; Laukkanen, E.; LeRiche, J.C.; Mueller, H.A.; Szasz, I.J.

    1987-11-01

    Preliminary results suggest that 3000 cGy radiation therapy alone offers only transient palliation for patients with obstructive endobronchial tumor. The addition of photodynamic therapy (PDT) prior to XRT provides significantly better and longer lasting local control. The combined treatment may also improve survival. It is possible that a therapeutic dose-6000 cGy radiation therapy may offer better local control than 3000 cGy.

  5. 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

  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. A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

    Science.gov (United States)

    Yu, Zhengze; Ge, Yegang; Sun, Qiaoqiao; Pan, Wei; Wan, Xiuyan; Li, Na; Tang, Bo

    2018-04-14

    Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen ( 1 O 2 ) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

  8. Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats.

    Science.gov (United States)

    Miyakogawa, Takayo; Kanai, Genta; Tatsumi, Ryoko; Takahashi, Hiroo; Sawada, Kaichiro; Kakuta, Takatoshi; Fukagawa, Masafumi

    2017-08-01

    Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT. A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp. PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days. Low-dose invasive PDT reduced intact parathyroid hormone (iPTH) levels in all rats from 748.9 ± 462.6 pg/mL at baseline to 138.7 ± 117.5 pg/mL at week 6, followed by a further decrease to 80.5 ± 54.0 pg/mL at week 9 in 60 % of rats or an increase to 970.0 ± 215.6 pg/mL at week 9 in 40 % of rats. Low-dose noninvasive PDT reduced iPTH levels from 1612.5 ± 607.8 pg/mL at baseline to 591.9 ± 480.1 pg/mL at week 4 in all rats. Thereafter, iPTH levels remained low in 43 % of rats and were 233.7 ± 51.6 pg/mL at week 9, whereas 57 % showed an increase, reaching 3305.9 ± 107.3 pg/mL at week 9. Control SHPT rats had iPTH levels of 2487.8 ± 350.9 and 2974.6 ± 372.1 pg/mL at week 4 and 9, respectively. The parathyroid glands of the rats with low iPTH levels were atrophied and had few parathyroid cells surrounded by fibrotic materials and no recognizable blood vessels. Those of the rats with high iPTH levels showed well-preserved gland structure, clusters of parathyroid cells, and blood vessels. These results demonstrate that 5-ALA-mediated PDT for SHPT is feasible.

  9. Photodynamic therapy (PDT and waterfiltered infrared A (wIRA in patients with recalcitrant common hand and foot warts

    Directory of Open Access Journals (Sweden)

    Hoffmann, Gerd

    2004-10-01

    Full Text Available Background: Common warts (verrucae vulgares are human papilloma virus (HPV infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT with 5-aminolevulinic acid (5-ALA in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA during 5-ALA-PDT revealed positive effects. Aim of the study: First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of "5-ALA cream (ALA vs. placebo cream (PLC" and "irradiation with visible light and wIRA (VIS+wIRA vs. irradiation with visible light alone (VIS". Methods: Pre-treatment with keratolysis (salicylic acid and curettage. PDT treatment: topical application of 5-ALA (Medac in "unguentum emulsificans aquosum" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun® radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: "Percent change of total wart area of each patient over the time" (18 weeks. Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales. 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups. Results: The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA and in group 2 (PLC

  10. 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).

  11. Supramolecular approach for target transport of photodynamic anticancer agents

    Czech Academy of Sciences Publication Activity Database

    Kejík, Z.; Kaplánek, R.; Bříza, T.; Králová, Jarmila; Martásek, P.; Král, V.

    2012-01-01

    Roč. 24, č. 2 (2012), s. 106-116 ISSN 1061-0278 R&D Projects: GA MŠk(CZ) LC06077; GA MŠk(CZ) 1M0520; GA ČR(CZ) GAP303/11/1291; GA ČR GA203/09/1311 Institutional research plan: CEZ:AV0Z50520514 Keywords : photodynamic therapy * photosensitisers * targeted transport * combination therapy * cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.546, year: 2012

  12. 5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol-chitosan copolymer for photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Chung CW

    2013-02-01

    Full Text Available Chung-Wook Chung,1,* Kyu-Don Chung,2,* Young-Il Jeong,1 Dae Hwan Kang,1 1National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University, Seoul, Republic of Korea*These authors contributed equally to this workPurpose: The aim of this study was to make 5-aminolevulinic acid (5-ALA-incorporated nanoparticles using methoxy polyethylene glycol/chitosan (PEG-Chito copolymer for application in photodynamic therapy for colon cancer cells.Methods: 5-ALA-incorporated (PEG-Chito-5-ALA nanoparticles were prepared by ion complex formation between 5-ALA and chitosan. Protoporphyrin IX accumulation in the tumor cells and phototoxicity induced by PEG-Chito-5-ALA nanoparticles were assessed using CT26 cells in vitro.Results: PEG-Chito-5-ALA nanoparticles have spherical shapes with sizes diameters 200 nm. More specifically, microscopic observation revealed a core-shell structure of PEG-Chito-5-ALA nanoparticles. 1H NMR spectra showed that 5-ALA was incorporated in the core of the nanoparticles. In the absence of light irradiation, all components such as 5-ALA, empty nanoparticles, and PEG-Chito-5-ALA nanoparticles did not affect the viability of cells. However, 5-ALA or PEG-Chito-5-ALA nanoparticles induced tumor cell death under light irradiation, and the viability of tumor cells was dose-dependently decreased according to the increase in irradiation time. In particular, PEG-Chito-5-ALA nanoparticles induced increased phototoxicity and higher protoporphyrin IX accumulation into the tumor cells than did 5-ALA alone. Furthermore, PEG-Chito-5-ALA nanoparticles accelerated apoptosis/necrosis of tumor cells, compared to 5-ALA alone.Conclusion: PEG-Chito-5-ALA nanoparticles showed superior delivery capacity of 5-ALA and phototoxicity against tumor cells. These results show that PEG-Chito-5-ALA

  13. High-sensitivity imaging method of singlet oxygen and superoxide anion in photodynamic and sonodynamic actions

    Science.gov (United States)

    Xing, Da; He, Yonghong; Hao, Min; Chen, Qun

    2004-07-01

    A novel method of photodynamic diagnosis (PDD) of cancer mediated by chemiluminescence (CL) probe is presented. The mechanism for photodynamic therapy (PDT) involves reactive oxygen species (ROS), such as singlet oxygen (1O2) and superoxide (O2-), generated by during the photochemical process. Both 1O2 and O2- can react with Cypridina luciferin analogue (FCLA), a highly selective CL probe for detecting the ROS. Chemiluminescence from the reaction of FCLA with the ROS, at about 530 nm, was detected by a highly sensitive ICCD system. The CL was markedly inhibited by the addition of 10 mmol/L sodium azide (NaN3) in a sample solution. Similar phenomena, with lesser extents of changes, were observed at the additions of 10 μmol/L superoxide dismutase (SOD), 10 mmol/L mannitol, and 100 μg/mL catalase, respectively. This indicates that the detected CL signals were mainly from ROS generated during the photosensitization reactions. Also, the chemiluminescence method was used to detect the ROS during sonodynamic action, both in vitro and in vivo. ROS formation during sonosensitizations of HpD and ATX-70 were detected using our newly-developed imaging technique, in real time, on tumor bearing animals. This method can provide a new means in clinics for tumor diagnosis.

  14. Pain in photodynamic therapy: mechanism of action and management strategies Dor na terapia fotodinâmica: mecanismo de ação e estratégias de manejo

    Directory of Open Access Journals (Sweden)

    Yuri Nogueira Chaves

    2012-08-01

    Full Text Available Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by irradiation with a light source at wavelengths matching the absorption spectrum of the photosensitizer. In many countries around the world, topical photodynamic therapy has been approved for treatment of cutaneous oncologic conditions such as actinic keratosis, Bowen's disease, and superficial basal cell carcinoma. Multicenter, randomized, controlled studies have confirmed its efficacy and superior cosmetic outcomes compared to conventional therapies. Nevertheless, this therapeutic method presents some adverse effects, such as erythema, edema, pigmentation, pustules, and pain. There is no doubt that pain is the most severe of the adverse effects, being sometimes responsible for definitive treatment interruption. The pain mechanism has not yet been fully understood, which makes complete pain control a challenge to be conquered. In spite of that, this literature review presents some useful pain management strategies as well as the most important pain-related factors in photodynamic therapy.A terapia fotodinâmica consiste na administração de uma droga fotossensibilizante e sua subseqüente irradiação com uma fonte de luz de espectro correspondente ao do seu fotossensibilizador. Em diversos países do mundo, a terapia fotodinâmica tópica é aprovada para o tratamento de condições oncológicas cutâneas como queratoses actínicas, doença de Bowen e carcinoma basocelular superficial. Estudos multicêntricos controlados e randomizados confirmam sua eficácia e seus resultados cosméticos superiores em relação às terapias convencionais. No entanto, existem alguns efeitos adversos inerentes a esse método terapêutico, como eritema, edema, pigmentação, pústulas e dor. Essa última é, sem dúvida, a mais importante deles, chegando a ser responsável pela interrupção definitiva do tratamento em alguns casos. O mecanismo dessa dor

  15. 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.

  16. 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.

  17. 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.

  18. Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas

    DEFF Research Database (Denmark)

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

    2015-01-01

    efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin...

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

    Science.gov (United States)

    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.

  20. Photodynamic dosimetry in the treatment of periodontitis

    Science.gov (United States)

    Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

    2009-06-01

    Photodynamic therapy has been demonstrated to effectively kill human periopathogens in vitro. However, the translation of in vitro work to in vivo clinical efficacy has been difficult due to the number of variables present in any given patient. Parameters such as photosensitizer concentration, duration of light therapy and amount of light delivered to the target tissue all play a role in the dose response of PDT in vivo. In this 121 patient study we kept all parameters the same except for light dose which was delivered at either 150 mW or 220 mW. This clearly demonstrated the clinical benefits of a higher light dose in the treatment of periodontitis.

  1. Real-Time Monitoring of Singlet Oxygen and Oxygen Partial Pressure During the Deep Photodynamic Therapy In Vitro.

    Science.gov (United States)

    Li, Weitao; Huang, Dong; Zhang, Yan; Liu, Yangyang; Gu, Yueqing; Qian, Zhiyu

    2016-09-01

    Photodynamic therapy (PDT) is an effective noninvasive method for the tumor treatment. The major challenge in current PDT research is how to quantitatively evaluate therapy effects. To our best knowledge, this is the first time to combine multi-parameter detection methods in PDT. More specifically, we have developed a set of system, including the high-sensitivity measurement of singlet oxygen, oxygen partial pressure and fluorescence image. In this paper, the detection ability of the system was validated by the different concentrations of carbon quantum dots. Moreover, the correlation between singlet oxygen and oxygen partial pressure with laser irradiation was observed. Then, the system could detect the signal up to 0.5 cm tissue depth with 660 nm irradiation and 1 cm tissue depth with 980 nm irradiation by using up-conversion nanoparticles during PDT in vitro. Furthermore, we obtained the relationship among concentration of singlet oxygen, oxygen partial pressure and tumor cell viability under certain conditions. The results indicate that the multi-parameter detection system is a promising asset to evaluate the deep tumor therapy during PDT. Moreover, the system might be potentially used for the further study in biology and molecular imaging.

  2. The mechanisms of photodynamic action for treating of cancer patients

    Directory of Open Access Journals (Sweden)

    A. L. Akopov

    2015-01-01

    Full Text Available Current views on mechanisms of therapeutic effect of photodynamic therapy for treating of cancer patients are represented. The history of formation and development of the method is described. The main requirements for agents used as photosensitizers are listed. Detailed review of main photosensitizers used in clinical practice in Russia and in foreign countries with their chemical structure, main spectral characteristics was performed. Methods of its application, therapeutic dose ranges, indications, specifi c pharmacokinetic properties and side-effects are briefl y outlined. Advantages and disadvantages of the most popular modern photosensitizers, main mechanisms of entry of photosensitizers of different chemical structure into cancer cells are observed. Three main possible component of anti-tumor effect: direct damage of cancer cells, impairment of vascular stroma of tumor and elimination of tumor due to immune cells are shown and closely discussed. Necrosis and apotosis of neovascular net which are main development trends of anti-tumor action for photodynamic therapy are noticed. 

  3. 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.

  4. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2015-08-01

    Full Text Available Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD and pathologic myopia (PM, both of which are frequently complicated by subfoveal choroidal neovascularization (CNV. Photodynamic therapy with verteporfin (PDT-V is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985 has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1 total number of photodynamic treatments; and (2 change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype received a higher number of photodynamic treatments than patients without it (GG wild-type genotype (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively. Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively. The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of

  5. 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.

  6. Clinical trial of pin-point photodynamic therapy using an optic fiber for the improvement of enlarged facial pores: a case study.

    Science.gov (United States)

    Kim, Sangeun; Cho, Kyeong-Hun

    2009-01-01

    There are few publications on the treatment options for facial pore size reduction. A focused therapy is needed. To evaluate the efficacy of selective photodynamic therapy (PDT) using an optic fiber for the size reduction of large facial pores. A series of five patients (skin phototypes IV-V) with large facial pores received two successive weekly treatments with an 810-nm diode laser using a fine optic fiber after indocyanine green (ICG) was applied selectively to enlarged pores. Patients were evaluated using digital photography at each treatment session, and at 3 months post-operation. Clinical assessment scores were determined at each treatment session and follow-up visit. Patient satisfaction surveys were obtained at the end of the study. All five participants who completed the 3-month follow-up gave a subjective assessment of reduction of facial pore size. Modest to excellent improvement was achieved. This study demonstrates that treatment with pin-point PDT using an optic fiber is a well-tolerated and effective regimen for the reduction of facial pore size.

  7. Photodynamic inactivation of foodborne bacteria by eosin Y.

    Science.gov (United States)

    Bonin, E; Dos Santos, A R; Fiori da Silva, A; Ribeiro, L H; Favero, M E; Campanerut-Sá, P A Z; de Freitas, C F; Caetano, W; Hioka, N; Mikcha, J M G

    2018-03-25

    The aim of this study was evaluate the effect of photodynamic inactivation mediated by eosin Y in Salmonella enterica serotype Typhimurium ATCC 14028, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778. Bacteria (10 7 CFU per ml) were incubated with eosin Y at concentrations ranging from 0·1 to 10 μmol l -1 , irradiated by green LED (λ max 490-570 nm) for 5, 10 and 15 min and the cellular viability was determined. Pseudomonas aeruginosa was completely inactivated when treated with 10 μmol l -1 eosin Y for 10 min. Treatments reduced B. cereus and Salm. Typhimurium counts to 2·7 log CFU per ml and 1·7 log CFU per ml, respectively. Escherichia coli counts were slightly reduced. Staphylococcus aureus presented the highest sensitivity, being completely inactivated by eosin Y at 5 μmol l -1 and 5 min of illumination. The reduction of cellular viability of photoinactivated Staph. aureus was also demonstrated by flow cytometry and morphological changes were observed by scanning electron microscopy. Eosin Y in combination with LED produced bacterial inactivation, being a potential candidate for photodynamic inactivation. This study evidenced the efficacy of photodynamic inactivation as a novel and promising alternative to bacterial control. © 2018 The Society for Applied Microbiology.

  8. Photodynamic damage of glial cells in crayfish ventral nerve cord

    Science.gov (United States)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2011-03-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  9. Lower sensitivity of FHC fetal colon epithelial cells to photodynamic therapy compared to HT-29 colon adenocarcinoma cells despite higher intracellular accumulation of hypericin

    Czech Academy of Sciences Publication Activity Database

    Mikeš, J.; Hýžďalová, Martina; Kočí, Lenka; Jendželovský, R.; Koval, J.; Vaculová, Alena; Hofmanová, Jiřina; Kozubík, Alois; Fedoročko, P.

    2011-01-01

    Roč. 10, č. 4 (2011), s. 626-632 ISSN 1474-905X R&D Projects: GA ČR(CZ) GA301/07/1557 Grant - others:GA ČR(CZ) GA305/09/1526 Program:GA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : photodynamic therapy * hypericin * colon cancer Subject RIV: BO - Biophysics Impact factor: 2.584, year: 2011

  10. 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.

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

    Science.gov (United States)

    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.

  12. 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.

  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. 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.

  15. 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