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  1. Pain in photodynamic therapy

    OpenAIRE

    Mircea Tampa; Maria Isabela Sârbu; Mădălina-Irina Mitran; Cristina-Iulia Mitran; Adrian Dumitru; Vasile Benea; Simona-Roxana Georgescu

    2016-01-01

    Photodynamic therapy is a modern treatment with applications in several medical specialties, which has been intensely studied in the last years. The main indications in dermatology are actinic keratosis, superficial basal cell carcinoma and Bowen's disease- common skin disorders in which photodynamic therapy proved its efficacy. At present, the use of photodynamic therapy for the treatment of other skin disorders is profoundly researched. Pain is the most common and redoubtable adverse effect...

  2. Pain in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Mircea Tampa

    2016-04-01

    Full Text Available Photodynamic therapy is a modern treatment with applications in several medical specialties, which has been intensely studied in the last years. The main indications in dermatology are actinic keratosis, superficial basal cell carcinoma and Bowen's disease- common skin disorders in which photodynamic therapy proved its efficacy. At present, the use of photodynamic therapy for the treatment of other skin disorders is profoundly researched. Pain is the most common and redoubtable adverse effect of photodynamic therapy and it is the most important factor affecting the patient's adherence to treatment. The aim of this article is to look over the most recent medical studies regarding pain in PDT, with emphasis on the factors affecting the occurrence of pain and the most recent strategies for controlling photodynamic therapy- related pain.

  3. Photodynamic therapy in dentistry.

    Science.gov (United States)

    Konopka, K; Goslinski, T

    2007-08-01

    Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemotherapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Applications of PDT in dentistry are growing rapidly: the treatment of oral cancer, bacterial and fungal infection therapies, and the photodynamic diagnosis (PDD) of the malignant transformation of oral lesions. PDT has shown potential in the treatment of oral leukoplakia, oral lichen planus, and head and neck cancer. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections. The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Disruption of plaque structure has important consequences for homeostasis within the biofilm. Studies are now leading toward selective photosensitizers, since killing the entire flora leaves patients open to opportunistic infections. Dentists deal with oral infections on a regular basis. The oral cavity is especially suitable for PACT, because it is relatively accessible to illumination. PMID:17652195

  4. Photodynamic therapy in dermatology

    Directory of Open Access Journals (Sweden)

    Nayak Chitra

    2005-01-01

    Full Text Available Photodynamic therapy is a new modality of therapy being used for the diagnosis and treatment of many tumors. It is now being increasingly used for skin tumors and other dermatological disorders. With its range of application it is certainly the therapy of the future. Its mechanism of action is by the Type II photo-oxidative reaction. The variables are the photosensitizer, the tissue oxygenation and the light source. It has been used to treat various disorders including Bowen′s disease, actinic keratoses, squamous cell carcinomas, basal cell carcinomas, and mycosis fungoides. The side-effects are fortunately mild and transient. Newer photosensitisers like methyl aminolevulinate hold a lot of promise for better therapy.

  5. Photodynamic therapy for epilepsy

    Science.gov (United States)

    Zusman, Edie; Sidhu, Manpreet; Coon, Valerie; Scott, Nicholas; Bisland, Stuart; Tsukamoto, Tara

    2006-02-01

    Epilepsy is surgically curable if the seizure focus can be localized and does not include areas of eloquent cortex. Because epileptic cells are indistinct from surrounding brain, resection typically includes normal tissue. Using the rat kindling model of epilepsy, we evaluated Photodynamic Therapy (PDT) as a super-selective lesioning technique. We present a series of pilot studies to evaluate: 1) Protoporphyrin IX (PpIX) fluorescence, 2) the efficacy of PDT to raise seizure thresholds, 3) the safety of PDT using behavioral studies, and 4) histologic results. Bipolar electrodes were chronically implanted into the cortex and animals received successive low-level stimulation generating seizures of increasing severity. Following 5-aminolevulinic acid (ALA) administration, fully kindled rats received electrical stimulation to induce a generalized seizure. Animals were irradiated with laser light focused onto a temporal craniectomy. Our results show: 1) an increase in PpIX fluorescence in the seizure group, 2) PDT treated animals failed to demonstrate seizure activity following repeat stimulation, 3) no statistically significant difference between treated and control animals were observed on behavioral tests, 4) histology showed pyknotic hippocampal pyramidal cells in the CA3 region without areas of obvious necrosis. In conclusion, this is the first report of heightened PpIX-mediated fluorescence in epileptic brain. The selective accumulation of PpIX with laser PDT may provide a less invasive and more precise technique for obliteration of epileptic foci. PDT warrants additional research to determine if this technique may augment or replace existing procedures for the surgical management of epilepsy.

  6. Photodynamic therapy in clinical practice

    OpenAIRE

    E. V. Filonenko; L. G. Serova

    2016-01-01

    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 a...

  7. Can nanotechnology potentiate photodynamic therapy?

    OpenAIRE

    Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Chung, Hoon; Yaroslavsky, Anastasia; Garcia-Diaz, Maria; Chang, Julie; Long Y. Chiang; Hamblin, Michael R.

    2012-01-01

    Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposom...

  8. Clinical Application of Photodynamic Therapy

    Institute of Scientific and Technical Information of China (English)

    LIU Hui-long; LIU Duan-qi

    2005-01-01

    Photodynamic therapy(PDT) is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source play important role in photodynamic therapy.PDT is a light activated chemotherapy. A photon is adsorbed by a photosensitizer which moves the drug into an excited state. The excited drug can then pass its energy to oxygen to create a chemical radical called "singlet oxygen". Singlet oxygen attacks cellular structures by oxidation. Such oxidative damage might be oxidation of cell membranes or proteins. When the accumulation of oxidative damage exceeds a threshold level,the cell begins to die.Photodynamic therapy allows selective treatment of localized cancer. PDT involves administration of a photosensitizer to the patients, followed by delivery of light to the cancerous region. The light activates the agent which kills the cancer cells. Without light,the agent is harmless.As a new therapy,photodynamic Therapy has great Advantage in treating cancers. 1. PDT avoids systemic treatment. The treatment occurs only where light is delivered, hence the patient does not undergo go needless systemic treatment when treating localized disease. Side-effects are avoided, from losing hair or suffering nausea to more serious complications. 2. PDT is selective. The photosensitizing agent will selectively accumulate in cancer cells and not in surrounding normal tissues.Hence ,there is selective targeting of the cancer and sparing of surrounding tissues.3. when surgery is not possible. PDT kills cancer cells but does not damage collagenous tissue structures,and normal cells will repopulate these structures. Hence,if a patient has cancer in a structure that cannot be removed surgically(eg. ,the upper bronchi of the lung) ,PDT can still treat the site. 4. PDT is repeatable. Unilke radiation therapy, PDT can be used again and again. Hence,it offers a means of longterm management

  9. Photodynamic therapy of diseased bone

    Science.gov (United States)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support

  10. 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.

  11. More Adventures in Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    David Kessel

    2015-07-01

    Full Text Available Photodynamic therapy is a procedure that can provide a selective eradication of neoplastic disease if sufficient drug, light, and oxygen are available. As this description suggests, it involves the photosensitization of malignant tissues to irradiation with photons in the visible range. While not suitable for tumors at unknown loci, it can be of use for eradication of cancer at surgical margins and therapy at sites where substantial surgery might otherwise be involved. Drug development has been delayed by several factors including the reluctance of major pharmaceutical firms in the United States to invest in this technology along with some unwise approaches in the past.

  12. 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. PMID:25719896

  13. 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. 

  14. Photodynamic Cancer Therapy - Recent Advances

    International Nuclear Information System (INIS)

    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

  15. 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.

  16. Broadband radiometry for photodynamic therapy

    Science.gov (United States)

    Folgosi-Correa, M. S.; Caly, J. P.; Nogueira, G. E. C.

    2010-04-01

    The effective irradiance is a useful measure to compare performances of different broadband light sources and to more precisely predict the outcome of a topical photodynamic therapy. The effective irradiance (or effective fluence rate) and the exposition time of the optical radiation usually determine the light dose. The effective irradiance (Eeff) takes into account the spectral irradiance of the source as well as the action spectrum, where the wavelength dependence of both optical diffusion through tissue and photosensitizer are considered. In practice there are no standard action spectra for the currently used photosensitizers. As a consequence, measured values of effective irradiance using different action spectra can not be compared. In order to solve this problem, the basis of the calibration theory developed for the broadband ultraviolet radiometry can be applied, where an experimental radiometer is compared with a standard radiometer. Here is presented a simple set of linear relations in the form Eeff = k . E, where E is the source irradiance and k a real positive value, here denoted as a characteristic of the radiometer, as valuable tools for correction of effective irradiances measured according to different action spectra. As a result, for two effective radiometers with different characteristics k1 and k2, measured values are Eeff and Qeff respectively, and it is easily shown that the value Eeff = Qeff • k1/k2 .

  17. Photodynamic therapy, new drugs, new lasers

    International Nuclear Information System (INIS)

    In the mid-1970's Dougherty and co-workers reintroduced hematoporphyrin derivative (HpD) as tumor localizer and photosensitizer for the detection and treatment of neoplastic disease. The efforts of this group led to the introduction of the combination of HpD and lasers for the treatment of a number of human neoplasms. During the late 1970's and throughout most of the 1980's efforts were made to determine the active component in the mixture of porphyrins which comprise HpO. The standard light source used in HpD was the argon-dye laser. Recently new photosensitizers for photodynamic therapy have been introduced. These newer photosensitizers are pure and not mixtures and are associated with less side effects than HpD. Concomitant with the development of new photosensitizers has been the development of new laser systems for photodynamic therapy. In this paper current developments in new drugs and new lasers for photodynamic therapy are presented

  18. Pain induced by photodynamic therapy of warts

    DEFF Research Database (Denmark)

    Stender, I-M; Borgbjerg, F Molke; Villumsen, J;

    2006-01-01

    Photodynamic therapy with topical 5-aminolevulinic acid (ALA), followed by irradiation with red light (ALA-PDT), is used for non-melanoma skin cancer and other dermatological diseases. Pain during and after light exposure is a well-known adverse advent that may be a limiting factor for treatment...

  19. 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

  20. Scope of photodynamic therapy in periodontics

    OpenAIRE

    Vivek Kumar; Jolly Sinha; Neelu Verma; Kamal Nayan; Saimbi, C. S.; 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...

  1. Photodynamic therapy with verteporfin for corneal neovascularization

    Directory of Open Access Journals (Sweden)

    Abdullah A Al-Torbak

    2012-01-01

    Results: At the last follow-up visit, 22 (66.7% eyes showed a decrease in corneal neovascularization and evidence of vascular thrombosis. Complete vascular occlusion was achieved in 14 (42.4% eyes, partial occlusion was achieved in 8 (24.2% eyes, and the vessels were patent in 11 (33.3% eyes. The corneal neovascularization score and depth of the vessels were found to be significant risk factors for failure (P = 0.0001 and 0.046, respectively. However, the diagnoses or causes of corneal neovascularisation were not statistically significant. No significant systemic or ocular complications associated with photodynamic therapy were observed. Conclusion: Photodynamic therapy with verteporfin was effective for the treatment of corneal neovascularization in the majority of the cases in this study.

  2. Photodynamic therapy for pododermatitis in penguins.

    Science.gov (United States)

    Sellera, Fábio Parra; Sabino, Caetano Padial; Ribeiro, Martha Simões; Fernandes, Loriê Tukamoto; Pogliani, Fabio Celidonio; Teixeira, Carlos Roberto; Dutra, Gustavo Henrique Pereira; Nascimento, Cristiane Lassálvia

    2014-01-01

    Pododermatitis is currently one of most frequent and important clinical complications in seabirds kept in captivity or in rehabilitation centers. In this study, five Magellanic penguins with previous pododermatitis lesions on their footpad were treated with photodynamic therapy (PDT). All PDT treated lesions successfully regressed and no recurrence was observed during the 6-month follow-up period. PDT seems to be an inexpensive and effective alternative treatment for pododermatitis in Magellanic penguins encouraging further research on this topic.

  3. Photodynamic therapy for occluded biliary metal stents

    Science.gov (United States)

    Roche, Joseph V. E.; Krasner, Neville; Sturgess, R.

    1999-02-01

    In this abstract we describe the use of photodynamic therapy (PDT) to recanalize occluded biliary metal stents. In patients with jaundice secondary to obstructed metal stents PDT was carried out 72 hours after the administration of m THPC. Red laser light at 652 nm was delivered endoscopically at an energy intensity of 50 J/cm. A week later endoscopic retrograde cholangiogram showed complete recanalization of the metal stent.

  4. Photodynamic therapy for pododermatitis in penguins.

    Science.gov (United States)

    Sellera, Fábio Parra; Sabino, Caetano Padial; Ribeiro, Martha Simões; Fernandes, Loriê Tukamoto; Pogliani, Fabio Celidonio; Teixeira, Carlos Roberto; Dutra, Gustavo Henrique Pereira; Nascimento, Cristiane Lassálvia

    2014-01-01

    Pododermatitis is currently one of most frequent and important clinical complications in seabirds kept in captivity or in rehabilitation centers. In this study, five Magellanic penguins with previous pododermatitis lesions on their footpad were treated with photodynamic therapy (PDT). All PDT treated lesions successfully regressed and no recurrence was observed during the 6-month follow-up period. PDT seems to be an inexpensive and effective alternative treatment for pododermatitis in Magellanic penguins encouraging further research on this topic. PMID:24888264

  5. Animal models for photodynamic therapy (PDT)

    OpenAIRE

    Silva, Zenildo Santos; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Huang, Ying-Ying; Hamblin, Michael R.

    2015-01-01

    Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for...

  6. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.

    Science.gov (United States)

    Torres, T; Fernandes, I; Costa, V; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  7. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma

    OpenAIRE

    Torres, T.; I. Fernandes; Costa, V.; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  8. Flexible textile light diffuser for photodynamic therapy

    Science.gov (United States)

    Selm, Barbel; Camenzind, Martin

    2005-03-01

    In this article a new medical application is introduced using textile production techniques to deliver a defined radiation dose. The advantage for photodynamic therapy (PDT) is that a flat luminous textile structure can homogeneously illuminate unequal body surfaces. The optical properties of this two-dimensional luminous pad are characterized with a set of bench-scale tests. In vitro investigations on petri dishes with cultivated cells and first clinical tests on animal patients are promising. In addition first measurement results are presented together with an outlook to future developments.

  9. [Photodynamic therapy for head and neck cancer

    DEFF Research Database (Denmark)

    Lajer, C.B.; Specht, Lena; Kirkegaard, J.;

    2006-01-01

    Photodynamic therapy (PDT) is a new treatment for head and neck cancer. The principle of the treatment is a photochemical reaction initiated by light activation of a photosensitizer, which causes the death of the exposed tissue. This article presents the modes of action of PDT and the techniques as...... well as the clinical procedure. A critical review of the literature is also presented, regarding treatment results of the different techniques and indications for treatments. The possibilities for PDT for head and neck cancer in Denmark are mentioned Udgivelsesdato: 2006/6/5...

  10. Hormonal component of tumor photodynamic therapy response

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush

    2008-02-01

    The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

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

    OpenAIRE

    Mladen eKorbelik; Judit eBanath; Kyi Min Saw; Wei eZhang; Evaldas eCilpys

    2015-01-01

    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 ...

  12. 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.

  13. Role of multidrug resistance in photodynamic therapy

    Science.gov (United States)

    Diddens, Heyke C.

    1992-06-01

    Multidrug resistance in cancer chemotherapy is a well established phenomenon. One of the most common phenotypical changes in acquired or intrinsic multidrug resistance in human tumor cells is the overexpression of the mdrl gene product P-glycoprotein, which acts as an active efflux pump. Increased levels of P-glycoprotein are associated with resistance to a variety of anticancer drugs commonly used in tumor chemotherapy like anthracyclins, vinca- alcaloids, epipodophyllotoxins or actinomycin D. We investigated the efficacy or photodynamic therapy in the treatment of tumor cells expressing the multidrug resistance phenotype. Our data show that multidrug resistant cells are highly cross resistant to the phototoxic stain rhodamine 123 but exhibit only low degrees of cross resistance (2 - 3 -folds) to the photosensitizers Photosan-3, Clorin-2, methylene blue and meso-tetra (4- sulfonatophenyl) porphine (TPPS4). Resistance is associated with a decrease in intracellular accumulation of the photosensitizer. Verapamil, a membrane active compound known to enhance drug sensitivity in multidrug resistant cells by inhibition of P-glycoprotein, also increases phototoxicity in multidrug resistant cells. Our results imply that tumors expressing the multidrug resistance phenotype might fail to respond to photochemotherapy with rhodamine 123. On the other hand, multidrug resistance may not play an important role in photodynamic therapy with Photosan-3, Chlorin-2, methylene blue or TPPS4.

  14. 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.

  15. Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

    OpenAIRE

    Meier, Daniela; Campanile, Carmen; Botter, Sander M.; Born, Walter; Fuchs, Bruno

    2014-01-01

    In recent years, there has been the difficulty in finding more effective therapies against cancer with less systemic side effects. Therefore Photodynamic Therapy is a novel approach for a more tumor selective treatment. Photodynamic Therapy (PDT) that makes use of a nontoxic photosensitizer (PS), which, upon activation with light of a specific wavelength in the presence of oxygen, generates oxygen radicals that elicit a cytotoxic response(1). Despite its approval almost twenty years ago by th...

  16. 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. PMID:26481895

  17. 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.

  18. Photodynamic therapy for port wine stains

    Science.gov (United States)

    Li, Junheng

    1998-11-01

    Previous therapies for port wine stains usually cause unacceptable scarring or obtain poor effect. Because port wine is a congenital vasculopathy consisting of an abnormal network of capillaries in the upper dermis with an overlying normal epidermis and the researchers found the tumor blood vessels were occluded accompanying the necrosis of the tumor after PDT. The author and his colleagues started a series of animal and clinical studies since 1991 about photodynamic therapy for port wine stain an they established the method of PDT for PWS. The clinical studies of over 1500 cases proved that PWS can be cured by PDT without scar formation because there is no thermal effect involved. No relapse was found within a maximum follow-up of six years.

  19. Photosensitizer and light diffusion through dentin in photodynamic therapy

    Science.gov (United States)

    Nogueira, Ana C.; Graciano, Ariane X.; Nagata, Juliana Y.; Fujimaki, Mitsue; Terada, Raquel S. S.; Bento, Antonio C.; Astrath, Nelson G. C.; Baesso, Mauro L.

    2013-05-01

    Photodynamic therapy has been considered a potential antimicrobial modality against oral infections, including dental caries. A model to estimate the penetration of both photosensitizers and light through human dentin, a factor of interest in photodynamic therapy, is proposed. The photoacoustic spectroscopy technique was used to evaluate in vitro dentin permeability of three different photosensitizers. Using the dentin optical absorption and scattering coefficients, it was possible to propose a semi-quantitative model predicting both photosensitizer and light doses within dentin. The graphic illustrations obtained provided guidelines that may be useful in photodynamic therapy protocols used as antimicrobial tools in caries lesions.

  20. Search for new photosensitizers in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    E. A. Lukiyanets

    2013-01-01

    Full Text Available The review of photosensityzers for photodynamic therapy and fluorescent diagnosis, which are being developed, investigated and applied in clinical practice in Russia and other countries, is represented. Principal properties of photosensitizers based on derivatives of hematoporfirin, chlorines, phtalocyanines, naphthalocyanines, benzoporphyrins, pheophorbides, porphycenes etc are described. Main drugs based on these agents are listed, the field of clinical application is indicated. Special consideration is given to phtalocyanines derivatives and its structural analogues. In particular Russian photosensitizers developed in Research Institute of Organic Intermediates and Dyes under the Program for development and health care practical assimilation of new methods and means of prevention, diagnosis and treatment of cancer, infection and other hazardous diseases are traversed in the article. Methods of synthesis are described, spectral, physical and biological characteristics of synthesized compounds are shown. 

  1. Intraoperative photodynamic therapy for larynx carcinomas

    Science.gov (United States)

    Loukatch, Erwin V.; Latyshevska, Galina; Fekeshgazi, Ishtvan V.

    1995-05-01

    We made an experimental and clinical researches to examine Intraoperative Photodynamic Therapy (IPT) as a method to prevent the recidives of tumors. In experimental researches on models with radio-inducated fibrosarcomas and Erlich carcinomas of mice the best method of IPT was worked out. The therapeutic effect was studied also on patients with laryngeal cancer. In researches on C3H mice the antirecidive effect of IPT established with local administration of methylene blue and Ar-laser. We found that IPT (He-Ne laser combined with methylene blue administration) was endured by patients with laryngeal cancers without problems. We got good results of treatment 42 patients with laryngeal cancers with middle localization during three years with using IPT method. This can show the perspectives of using this method in treatment of other ENT-oncological diseases.

  2. Photodynamic therapy of different photosensitizers in leukemia

    Science.gov (United States)

    Zhang, Sujuan; Zhang, Zhenxi; Jiang, Dazong

    2002-04-01

    Photodynamic therapy (PDT), a cancer treatment using a photosensitizer and visible light has been applied to treatment of blood cancer-leukemia. The effect of PDT may be modulated by the leukemia cell type; the photosensitizer's type, dose, dose rate changes; the incubation time; the light wavelength, dosage, dose rate change; the conjugation of photosensitizers to variety subcellular target: cell membrane, mitochondia, lipoprotein or liposome; the addition of chemotherapeutic agents et al. Many reports in the current literature are confusing and often apparently contradictory. In this article, we have attempted to conduct and present a comprehensive review of this rapidly expanding novel field in a range of photosensitizers. Cell types, photosensitizers, treatment conditions and mechanism of PDT are considered. Nonetheless, there is ample ground for optimism, and such knowledge as we already have should effectively underpin the clinical research that is ongoing.

  3. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    OpenAIRE

    L.A. Muehlmann; G.A. Joanitti; Silva, J.R.; J.P.F. Longo; Azevedo, R B

    2011-01-01

    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 th...

  4. Interstitial photodynamic laser therapy in interventional oncology

    International Nuclear Information System (INIS)

    Photodynamic therapy (PDT) is a well-investigated locoregional cancer treatment in which a systemically administered photosensitizer is activated locally by illuminating the diseased tissue with light of a suitable wavelength. PDT offers various treatment strategies in oncology, especially palliative ones. This article focuses on the development and evaluation of interstitial PDT for the treatment of solid tumors, particularly liver tumors. The PDT is mostly used for superficial and endoluminal lesions like skin or bladder malignancies and also more frequently applied for the treatment of lung, esophageal, and head and neck cancer. With the help of specially designed application systems, PDT is now becoming a practicable option for solid lesions, including those in parenchymal organs such as the liver. After intravenous treatment with the photosensitizer followed by interstitial light activation, contrast-enhanced computed tomography shows the development of therapy-induced necrosis around the light-guiding device. With the use of multiple devices, ablation of liver tumors seems to be possible, and no severe side effects or toxicities related to the treatment are reported. PDT can become a clinically relevant adjunct in the locoregional therapy strategies. (orig.)

  5. Photodynamic therapy for treatment of head and neck cancer.

    Science.gov (United States)

    Schweitzer, V G

    1990-03-01

    Since 1975, photodynamic therapy has reportedly been effective in a variety of head and neck malignancies that failed traditional (conventional) therapy, including surgery, cryotherapy, chemotherapy, hyperthermia, and radiation therapy. Photodynamic therapy consists of the intravenous administration of (di)hematoporphyrin ether, a chemosensitizing drug selectively retained by neoplastic and reticuloendothelial tissues which, when exposed to a 630-nm argon laser, catalyzes a photochemical reaction to release free oxygen radicals, "the cytotoxic" agents responsible for cell death and tumor necrosis. Preliminary investigations have assessed the efficacy of photodynamic therapy in treatment of: (1) superficial "condemned mucosa" or "field cancerization" of the oral cavity and (2) stage III and IV head and neck carcinomas that had unsuccessful conventional therapy. Complete and/or partial remissions were obtained in 11 of 12 patients (16 treatments) with a variety of carcinomas of the nasopharynx, palate and uvula, retromolar trigone, temporal bone, cervical esophagus, and AIDS-related Kaposi's sarcoma of the oral cavity. PMID:2108409

  6. Combination immunotherapy and photodynamic therapy for cancer

    Science.gov (United States)

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

    2006-02-01

    Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

  7. 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.

  8. Photodynamic Therapy for Malignant Brain Tumors.

    Science.gov (United States)

    Akimoto, Jiro

    2016-04-15

    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. PMID:26888042

  9. 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.

  10. Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Arjen F. Nikkels

    2010-06-01

    Full Text Available Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methyl-aminolevulinate (MAL based photodynamic therapy (PDT resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence. Although spontaneous regression of cutaneous Langerhans cell histiocytosis is observed, the rapid effect of photodynamic therapy after several failures of other treatment suggests that photodynamic therapy was successful. As far as we know this is the first report of photodynamic therapy for refractory skin lesions. Larger series are needed to determine whether photodynamic therapy deserves a place in the treatment of multiresistant cutaneous Langerhans cell histiocytosis.

  11. Photodynamic therapy of advanced malignant tumors

    Science.gov (United States)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  12. Photodynamic laser therapy in tracheo bronchial endoscopy

    International Nuclear Information System (INIS)

    Hp and HpD have been found to be accumulated and retained by tumor tissues; intravenous Hp or HpD disseminates throughout the entire body, but it rapidly clears out of the normal cells, while remaining longer in tumor tissue, where it is 5-6 times more concentrated after 48-72 hours. Photo-Dynamic Therapy is based upon specific photosensitization of malignant tissue containing Hp after exposure to a visible activating light in the red region of the spectrum (630 nm). Absorption in the red allows deep penetration into tissue, biological effects of using this wavelength are in the order of 5-15 mm of tumor tissue thickness. Photosensitization produces a photochemical reaction releasing singlet Oxygen, that causes tissue death. The singlet Oxygen damages some biological processes such as replay and repair of nucleic acids, cell respiration, protein synthesis and cell membrane function. How-ever, the tissue damage is caused by involvement of the tumor microvascular system too. Many authors report that effects of PDT are secondary to the destruction of tumor microvasculature and the first observable signs occur in the subendothelial zone of the tumor capillary wall. PDT is effective in tracheobronchial endoscopy in treatment of precancerous lesions and early stage lung cancer. PDT has been employed in treatment of advanced carcinoma associated with YAG-Laser and Radiotherapy. (author). 29 refs., 1 tab

  13. Pecularities of clinical photodynamic therapy of cancer

    Science.gov (United States)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.; Litvin, Grigory D.; Astrakhankina, Tamara A.

    1996-01-01

    The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder rectum and other locations has been made. During 1992 - 1995 478 tumoral foci in 125 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect 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. Two home-made preparations were used as photosensitizers: Photohem (hematoporphyrine derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were: the argon pumped dye laser (`Innova-200', `Coherent') and home-made laser devices: copper-vapor laser-pumped dye laser (`Yakhroma-2', Frjazino), gas-discharge unit `Ksenon' (wavelength 630 nm), gold-vapor laser (wavelength 627.8 nm) for Photohem; while for Photosense sessions we used solid-state laser on ittrium aluminate `Poljus-1' (wavelength 670 nm). Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 92% of patients including complete regression of tumors in 66.4% and partial in 25.6%. 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.

  14. Photodynamic therapy (PDT) as a biological modifier

    Science.gov (United States)

    Obochi, Modestus; Tao, Jing-Song; Hunt, David W. C.; Levy, Julia G.

    1996-04-01

    The capacity of photosensitizers and light to ablate cancerous tissues and unwanted neovasculature constitutes the classical application of photodynamic therapy (PDT). Cell death results from either necrotic or apoptotic processes. The use of photosensitizers and light at doses which do not cause death has been found to affect changes in certain cell populations which profoundly effect their expression of cell surface molecules and secretion of cytokines, thereby altering the functional attributes of the treated cells. Cells of the immune system and the skin may be sensitive to modulation by 'sub-lethal PDT.' Ongoing studies have been conducted to assess, at the molecular level, changes in both lymphocytes and epidermal cells (EC) caused by treatment with low levels of benzoporphyrin derivative monoacid ring A (BPD) (a photosensitizer currently in clinical trials for cancer, psoriasis, endometriosis and age-related macular degeneration) and light. Treatment of skin with BPD and light, at levels which significantly enhanced the length of murine skin allograft acceptance, have been found to down-regulate the expression of Langerhans cell (LC) surface antigen molecules [major histocompatibility complex (MHC) class II and intracellular adhesion molecule (ICAM)-1] and the formation of some cytokines (tumor necrosis factor-alpha (TNF- (alpha) ).

  15. PDT dose dosimeter for pleural photodynamic therapy

    Science.gov (United States)

    Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.

    2016-03-01

    PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry.

  16. Photodynamic therapy of symptomatic choroidal nevi

    Directory of Open Access Journals (Sweden)

    Luis Amselem

    2011-01-01

    Full Text Available Purpose : To evaluate the role of photodynamic therapy (PDT for patients with symptomatic choroidal nevi involving the fovea or located near the fovea with subretinal fluid extending to the fovea. Materials and Methods : Retrospective review of five patients who underwent PDT for choroidal nevi at two separate centers in Ankara and Barcelona. Results : The mean initial logMAR visual acuity was 0.5 (range: 0 to 1.5. The mean largest tumor base diameter was 3.2 mm (range: 2.1-4.5 mm and the mean tumor thickness was 1.1 mm (range: 0.7-1.6 mm. The mean number of PDT sessions was 1.6 (range:1-3. The mean final tumor thickness was 1.0 mm (range: 0-1.6 mm at a mean follow-up of 19 months (range: 12-32 months. The mean final logMAR visual acuity was 0.4 (range: 0-1.5. Subfoveal fluid disappeared or decreased significantly in 4 of 5 eyes (80% after PDT. Conclusions : PDT led to resolution of subretinal fluid with preservation of visual acuity in many symptomatic choroidal nevi in this study. Careful case selection is important as PDT of indeterminate pigmented tumors may delay the diagnosis and treatment of an early choroidal melanoma and thereby increase the risk for metastasis.

  17. Photodynamic therapy: Biophysical mechanisms and molecular responses

    Science.gov (United States)

    Mitra, Soumya

    In photodynamic therapy (PDT), photochemical reactions induced by optical activation of sensitizer molecules cause destruction of the target tissue. In this thesis we present results of several related studies, which investigated the influence of photophysical properties and photobleaching mechanisms of sensitizers and oxygen-dependent tissue optical properties on PDT treatment efficacy. The bleaching mechanism of the sensitizer meso-tetra hydroxyphenyl chlorin (mTHPC) is examined indirectly using measurements of photochemical oxygen consumption during PDT irradiation of multicell tumor spheroids. Analysis of the results with a theoretical model of oxygen diffusion that incorporates the effects of sensitizer photobleaching shows that mTHPC is degraded via a singlet-oxygen (1O2)-mediated bleaching process. The analysis allows us to extract photophysical parameters of mTHPC which are used to account for its enhanced clinical photodynamic potency in comparison to that of Photofrin. Evaluation of the spatially-resolved fluorescence in confocal optical sections of intact spheroids during PDT irradiation allows for the direct experimental verification of mTHPC's 1O2-mediated bleaching mechanism. The technique is also used to investigate the complex bleaching kinetics of Photofrin. The results allow us to successfully reconcile apparently contradictory experimental observations and to confirm the predictions of a new theoretical model in which both 1O2 and excited triplet sensitizer molecules are allowed to contribute to photobleaching. Based on studies performed in tissue-simulating erythrocyte phantoms and in a murine tumor model in vivo, we present clinically relevant results which indicate that a shift toward increased hemoglobin-oxygen saturation due to improved tissue oxygenation reduces PDT treatment beam attenuation and may allow for more effective treatment of deeper lesions. Finally, we investigate the induction of the stress protein, heat shock protein 70 (HSP

  18. Photodynamic therapy for cutaneous metastases of breast cancer

    Directory of Open Access Journals (Sweden)

    E. V. Goranskaya

    2011-01-01

    Full Text Available Breast cancer is the most common cancer and the leading cause of cancer death in w omen. Cutaneous metastases are observed in 20 % pa- tients with breast cancer. 36 breast cancer patients with cutaneous metastases were treated with photodynamic therapy in the de partment of laser and photodynamic therapy MRRC. Complete regression was obtained in 33.9 %, partial — in 39 % of cases, the stabilization achieved in 25.4 %, progression noted in 1.7 %. The objective response was obtained in 72.9 % of cases, treatment effect — in 97.4 %. Photodynamic therapy has good treatment results of cutaneous metastases of breast cancer with a small number of side effects.

  19. Important cellular targets for antimicrobial photodynamic therapy.

    Science.gov (United States)

    Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

    2016-09-01

    The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets. PMID:27221289

  20. New strategies to enhance photodynamic therapy for solid tumors

    OpenAIRE

    Gulik, van der, T.; Heger, M.; Broekgaarden, M.

    2016-01-01

    Photodynamic therapy for cancer uses laser light to specifically activate anti-cancer drugs at the tumor site. However, this potentially effective and patient-friendly therapy has seen limited clinical application due to the inability of these drugs to accumulate at the tumor site and the subsequent survival of the malignancy. The aim of this research was to find out how tumor cells survive this therapy, to develop drug delivery systems that target the anti-cancer drugs towards the tumor site...

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

    OpenAIRE

    Lim, Hyun Soo

    2011-01-01

    Background and Aims: 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.

  2. Fiber Optic Spectroscopy for the Optimization of Photodynamic Therapy

    NARCIS (Netherlands)

    F. van Leeuwen- van Zaane (Floor)

    2014-01-01

    markdownabstract__Abstract__ Photodynamic therapy (PDT) is a treatment modality for cancer and premalignant lesions that utilizes a photoactive drug, the photosensitizer, in combination with light. PDT has become the treatment of choice for various malignancies. Furthermore, PDT is under investigat

  3. Pretreatment to enhance protoporphyrin IX accumulation in photodynamic therapy.

    NARCIS (Netherlands)

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

    2009-01-01

    The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an impo

  4. Nanobody-photosensitizer conjugates for targeted photodynamic therapy

    NARCIS (Netherlands)

    Heukers, Raimond; van Bergen en Henegouwen, P; Santos 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 t

  5. Cutaneous leishmaniasis responds to daylight-activated photodynamic therapy

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Israel, with hundreds of new cases reported in recent years. Photodynamic therapy (PDT) is highly effective for treatment of CL, but requires equipment available only at specialized centres. Daylight-activated PDT (DA-PDT) abolishes the need...

  6. A new paradigm for photodynamic therapy: coherent control

    NARCIS (Netherlands)

    Yang, Di; Savolainen, Janne; Jafarpour, Aliakbar; Sprünken, Daan P.; Herek, Jennifer L.; Kessel, David H.

    2009-01-01

    Photodynamic therapy (PDT) is a treatment based on the interaction of light, photosensitizing agents and tissue oxygen. The light delivery in PDT is usually optimized by controlling the intensity, the spectrum, and/or the dosage of excitation light. In this paper, we introduce a novel method that ai

  7. 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 photosensiti

  8. Enhancement of selectivity for photodynamic therapy

    Science.gov (United States)

    Bedwell, Joanne

    Photodynamic Therapy (PDT) is a technique for producing localised tissue damage with low power light following prior administration of a photosensitising drug. The promise of PDT has been based on the selective retention of photosensitisers by tumours, but this aspect has been over-emphasised with a maximum ratio of photosensitiser concentration of 3:1, tumour to normal, for extracranial tumours and current drugs. This makes selective tumour necrosis difficult to achieve. This thesis explores ways in which selectivity may be improved. Aluminium sulphonated phthalocyanine (AlSPc) has better photochemical properties than the widely used HpD and Photofrin II, but has the same tumour selectivity, although the ratio was improved marginally using its disulphonated component. However, when used in conjunction with the radioprotective drug W7, in a rat colon cancer model, tumour necrosis was the same as without W7 while there was no damage to adjacent normal colon. A radical new approach is to give 5-aminolaevulinic acid (ALA) which induces endogenous production of the photosensitiser protoporphyrin IX. This improves selectivity in the rat colon cancer to 6:1 (tumour to normal mucosa), but also sensitises the mucosa selectively compared with the underlying muscle (10:1), giving a tumour to muscle ratio of 60:1. This has enormous potential for treating small tumours or areas of dysplasia in a range of hollow organs. ALA also has the major advantages of a short optimum drug to light time (typically 4-6 hours), short duration of skin sensitivity (approximately 24 hours) and it can be given orally with minimal systemic toxicity. This work has also shown in vitro that PDT with AlSPc sensitisation can kill helicohacter pylori at doses unlikely to affect gastric mucosa. In conclusion, by careful choice of photosensitising agents and treatment regimes, it is possible to limit PDT effects to abnormal tissues, and even if there is some normal tissue damage, in most cases, this heals

  9. 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.

  10. Effects of telomerase expression on photodynamic therapy of Barrett's esophagus

    Science.gov (United States)

    Wang, Kenneth K.; Anderson, Marlys; Buttar, Navtej; WongKeeSong, Louis-Michel; Borkenhagen, Lynn; Lutzke, Lori

    2003-06-01

    Photodynamic therapy has been applied to Barrett's esophagus and has been shown in prospective randomized studies to eliminate dysplasia as well as decrease the occurrence of cancer. However, the therapy isnot always effective and there are issues with residual areas of Barrett's mucosa despite therapy. There has not been a good explanation for these residual areas and they seem to imply that there may exist a biological mechanisms by which these cells may be resistant to photodynamic therapy. It was our aim to determine if known abnormalities in Barrett's mucosa could be correlated with the lack of response of some of these tissues. We examined the tissue from mulitpel patients who had resonse to therapy as well as those who did not respond. We assessed the tissue for p53 mutations, inactivatino of p16, ploidy status, cell proliferation, telomerase activity, and degree of dysplasia. Interestingly, the only genetic marker than was found to be correlated with lack of reonse was p53 and telomerase activity. This suggests that cells that have lost mechanisms for cell death such as apoptosis or telomere shortengin may be more resistant to photodynamic therapy. In this study, we examined patients before and after PDT for telomerase activity.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  12. Photodynamic therapy for chest wall recurrence from breast cancer.

    Science.gov (United States)

    Allison, R R; Sibata, C; Mang, T S; Bagnato, V S; Downie, G H; Hu, X H; Cuenca, R

    2004-09-01

    Breast cancer is common with over 230,000 new cases diagnosed each year in North America alone. While great strides have been made to achieve excellent cancer control and survival, a significant minority of patients fail locally. While initial salvage to regain disease control is of the utmost importance, it is not universally successful. This leads to a therapeutic quagmire. Additional surgery, radiation and chemo-hormonal therapy are possible, but they are usually highly morbid with low success rates. Photodynamic therapy appears to be an underutilized salvage modality for this unfortunate patient population. This report analyzes and reviews the role of photodynamic therapy for patients with chest wall re-recurrence from breast cancer.

  13. Nanotechnology; its significance in cancer and photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Gaeeni

    2015-07-01

    Full Text Available In the last decade, developments in nanotechnology have provided a new field in medicine called “Nanomedicine”. Nanomedicine has provided new tools for photodynamic therapy. Quantum dots (QDs are approximately spherical nanoparticles that have attracted broad attention and have been used in nanomedicine applications. QDs have high molar extinction coefficients and photoluminescence quantum yield, narrow emission spectra, broad absorption, large effective stokes shifts. QDs are more photostable and resistant to metabolic degradation. These photosensitizing properties can be used as photosensitizers for Photodynamic Therapy (PDT. PDT has been recommended for its unique characteristic, such as low side effect and more efficiency. Therefore, nanomedicine leads a promising future for targeted therapy in cancer tumor. Furthermore, QDs have recently been applied in PDT, which will be addressed in this review letter. Also this review letter evaluates key aspects of nano-particulate design and engineering, including the advantage of the nanometer scale size range, biological behavior, and safety profile.

  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. Photodynamic Therapy for Extramammary Paget's Disease:5 Cases Report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study the therapeutic effect of photodynamic therapy for extramammary Paget's disease.Methods: DIOMED 630 nm diode laser was used as light source and photofrin as photosensitizer. The patient's lesion was irradiated for 24-72 h after administrating of photofrin. The power density was 100-150 mW/cm2 and energy density was 150-300J/cm2. Dosage of photofrin was 2 mg/kg. Results: Lesion darkened 24 h after irradiation and formed a scar 96-120 h after irradiation. One patient's lesion disappeared, three patients' lesion diminished apparently and one patient's lesion was not controlled 3 months later. Conclusion: Photodynamic therapy is an effective modality for extramammary Paget's disease.

  16. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    Science.gov (United States)

    Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

    2005-07-01

    To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

  17. Simultaneous two-photon excitation of photodynamic therapy agents

    Energy Technology Data Exchange (ETDEWEB)

    Wachter, E.A.; Fisher, W.G. [Oak Ridge National Lab., TN (United States)]|[Photogen, Inc., Knoxville, TN (United States); Partridge, W.P. [Oak Ridge National Lab., TN (United States); Dees, H.C. [Photogen, Inc., Knoxville, TN (United States); Petersen, M.G. [Univ. of Tennessee, Knoxville, TN (United States). College of Veterinary Medicine

    1998-01-01

    The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type 1 and type 2 photodynamic therapy (PDT) agents are examined.

  18. Photodynamic therapy for basal cell skin cancer ENT-organs

    Directory of Open Access Journals (Sweden)

    V. N. Volgin

    2014-01-01

    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  19. Photodynamic therapy for the treatment of buccal candidiasis in rats.

    Science.gov (United States)

    Junqueira, Juliana Campos; Martins, Joyce da Silva; Faria, Raquel Lourdes; Colombo, Carlos Eduardo Dias; Jorge, Antonio Olavo Cardoso

    2009-11-01

    The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P-); treated only with photosensitizer (L--P+); not treated with laser or photosensitizer (L-P-). The rats were killed immediately, 1 day, or 5 days after treatment, for microscopic analysis of the tongue dorsum. Observation verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial alterations and a lower chronic inflammatory response than the L-P- group. The group L+P- presented more intense epithelial alterations and chronic inflammatory response than the remaining groups. The L-P+ group showed tissue lesions similar to those of the L-P- group. In conclusion, rats treated with photodynamic therapy developed more discrete candidiasis lesions than did the remaining groups.

  20. Latex carrier for improving protoporphyrin IX for photodynamic therapy.

    Science.gov (United States)

    Bui, Brian; Liu, Li; Chen, Wei

    2016-06-01

    Attachment of Protoporphyrin IX (PPIX) to poly (styrene-co-4-vinylpyridine) (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions. After using an oil-in-water heated emulsion polymerization technique to synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing self-reactions between the carboxyl groups and the porphyrin core. Refraining the two parts from interacting while attached to the nanobeads prevented PPIX from aggregating, which then increased water solubility, enhanced luminescence and singlet oxygen production. Attachment also improved cell uptake and cell destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve aspects of photodynamic therapy for the treatment of cancer. PMID:27020668

  1. Intraoperative photodynamic therapy in laryngeal part of pharynx cancers

    Science.gov (United States)

    Loukatch, Erwin V.; Trojan, Vasily; Loukatch, Vjacheslav

    1996-12-01

    In clinic intraoperative photodynamic therapy (IPT) was done in patients with primal squamous cells cancer of the laryngeal part of the pharynx. The He-Ne laser and methylene blue as a photosensibilizator were used. Cobalt therapy in the postoperative period was done in dose 45 Gr. Patients of control groups (1-th group) with only laser and (2-th group) only methylene blue were controlled during three years with the main group. The statistics show certain differences of recidives in the main group compared to the control groups. These facts are allowing us to recommend the use of IPT as an additional method in ENT-oncology diseases treatment.

  2. 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....... To be able to apply these results in other parts of the world we have to compare the daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light doses found in Nordic countries....

  3. Sonodynamic therapy with photosensitizers and its combination with photodynamic therapy in treatment of malignant tumors

    Directory of Open Access Journals (Sweden)

    D. A. Zerkovskiy

    2014-01-01

    Full Text Available The article reviews mechanisms of sonodynamic therapy with photosensitizers (ultrasound + photosensitizer and combination of sonodynamic with photodynamic therapy (ultrasound + photosensitizer + light exposure for treatment of malignant tumors. Efficacy of these methods with photosensitizers of different chemical structure in experimental study in vitro and in vivo on different tumor models and in clinical trials was assessed. 

  4. Effect of photodynamic therapy combined with intravitreal injection of Lucentis therapy on choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei Su

    2016-01-01

    Objective:To analyze the efficacy of photodynamic therapy combined with intravitreal injection of Lucentis therapy for choroidal neovascularization.Methods: A total of 82 cases with choroidal neovascularization receiving inpatient therapy in our hospital from August 2013 to August 2014 were selected as research subjects, and according to random number table method, all enrolled patients were divided into control group (received photodynamic therapy) and observation group (received photodynamic therapy combined with intravitreal injection of Lucentis therapy), each group with 41 cases. Differences in best corrected visual acuity, intraocular pressure and central macular thickness, mean sensitivity of visual field and so on of two groups were compared.Results:After treatment, visual acuity improvement ratio of observation group was significantly higher than that of control group and visual acuity decrease ratio was lower than that of control group (P<0.05); intraocular pressure and central macular thickness were significantly less than those of control group (P<0.05); mean sensitivity of 10o and 30o visual field was higher than that of control group (P<0.05).Conclusions:Photodynamic therapy combined with intravitreal injection of Lucentis therapy can effectively improve vision and visual acuity of patients with choroidal neovascularization and reduce intraocular pressure and central macular thickness; it is an ideal treatment method.

  5. 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

    2016-01-01

    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.

  6. 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

    2016-01-01

    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. PMID:26978341

  7. 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.

  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. 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.

  10. HpD Photobiology And Photodynamic Therapy Of Bladder Carcinoma

    Science.gov (United States)

    Lin, Chi-Wei

    1988-02-01

    Bladder carcinoma is considered one of the most favorable targets for the application of photodynamic therapy (PDT) due to the accessibility of the bladder for light delivery. Examination of the bladder and surgical procedures are routinely performed by the insertion of an optical instrument called cystoscope through the urethra. Thus, the treatment of bladder cancer by PDT can be conducted through the cystoscope with minimal invasion. However, to achieve optimal results from this treatment, one must consider both the structure of the bladder and the nature of the carcinoma.

  11. 3D Monte Carlo radiation transfer modelling of photodynamic therapy

    Science.gov (United States)

    Campbell, C. Louise; Christison, Craig; Brown, C. Tom A.; Wood, Kenneth; Valentine, Ronan M.; Moseley, Harry

    2015-06-01

    The effects of ageing and skin type on Photodynamic Therapy (PDT) for different treatment methods have been theoretically investigated. A multilayered Monte Carlo Radiation Transfer model is presented where both daylight activated PDT and conventional PDT are compared. It was found that light penetrates deeper through older skin with a lighter complexion, which translates into a deeper effective treatment depth. The effect of ageing was found to be larger for darker skin types. The investigation further strengthens the usage of daylight as a potential light source for PDT where effective treatment depths of about 2 mm can be achieved.

  12. Photodynamic Therapy for Bowen's Disease of the Vulva Area

    OpenAIRE

    Kang, Hong-Kyu; Yun, Jeong-Hwan; Son, Young-Min; Roh, Joo-Young; Lee, Jong-Rok

    2014-01-01

    Bowen's disease is a squamous cell carcinoma in situ and has the potential to progress to a squamous cell carcinoma. The authors treated two female patients (a 39-year-old and a 41-year-old) with Bowen's disease in the vulva area using topical photodynamic therapy (PDT), involving the use of 5-aminolaevulinic acid and a light-emitting diode device. The light was administered at an intensity of 80 mW/cm2 for a dose of 120 J/cm2 biweekly for 6 cycles. The 39-year-old patient showed excellent cl...

  13. Photodynamic therapy with laser scanning mode of tumor irradiation

    Science.gov (United States)

    Chepurna, Oksana; Shton, Irina; Kholin, Vladimir; Voytsehovich, Valerii; Popov, Viacheslav; Pavlov, Sergii; Gamaleia, Nikolai; Wójcik, Waldemar; Zhassandykyzy, Maral

    2015-12-01

    In this study we propose a new version of photodynamic therapy performed by laser scanning. The method consists in tumor treatment by a light beam of a small cross section which incrementally moves through the chosen area with a defined delay at each point and repetitively re-scans a zone starting from the initial position. Experimental evaluation of the method in vitro on murine tumor model showed that despite the dose, applied by scanning irradiation mode, was 400 times lower, the tumor inhibition rate conceded to attained with continuous irradiation mode by only 20%.

  14. Hardware and tool equipment for fluorescence diagnostics and photodynamic therapy

    Directory of Open Access Journals (Sweden)

    V. B. Loschenov

    2013-01-01

    Full Text Available The results of hardware and tool development in photodynamic therapy and fluorescence diagnostics performed by the Natural Research Center, A.M. Prokhorov General Physics Institute, Russian Academy of Sciences in collaboration with several research and medical institutes are presented. Physical and technical aspects of the problem are mentioned. We describe schemes and the principle of operation of devices which we use with our medical colleagues in clinical and experimental studies. Some results of clinical use of the developed devices and methods are presented. 

  15. Photodynamic therapy of port wine stain: preliminary clinical studies

    Science.gov (United States)

    Nelson, J. Stuart

    1993-07-01

    The broad, long term objective of this work is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with port wine stain (PWS). PDT involves the use of an exogenous drug which is concentrated in a targeted tissue. When irradiated at wavelengths specifically absorbed by the drug, selective destruction of the targeted tissue, without the production of heat, occurs. The results of this preliminary study demonstrate in human PWS patients that a photosensitizer, such as PHOTOFRINR, activated by red light at the appropriate therapeutic wavelength, can cause destruction of subsurface blood vessels in the skin with a high degree of specificity, and further study appears warranted.

  16. Dramatic regression of presumed acquired retinal astrocytoma with photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Samuray Tuncer

    2014-01-01

    Full Text Available Photodynamic therapy (PDT has been used for treatment of various intraocular tumors including choroidal hemangioma, vasoproliferative tumor, amelanotic choroidal melanoma and choroidal neovascular membrane due to choroidal osteoma. This case report documents the effect of PDT for a presumed acquired retinal astrocytoma. A 42-year-old female with a juxtapapillary acquired astrocytoma was treated with a single session of PDT using standard parameters. The tumor showed dramatic regression over 6 months into a fibrotic scar. It remained regressed and stable with 20/20 vision after 51 months of follow-up. We believe that PDT can be used as a primary treatment for acquired retinal astrocytoma.

  17. Effects of Photodynamic Therapy on the Ultrastructure of Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To study the change in ultrastructure of C6 glioma cells after photodynamic therapy (PDT), to compare morphological differences in necrosis and apoptosis before and after PDT treatment, and to evaluate the effect of photodynamic therapy on the blood brain tumor barrier (BTB) of C6 glioma. Methods The model was produced by transplanting C6 glioma cells cultured in vitro using Peterson method into the caudate nuclei of Wister rats. The experiment group received PDT for two weeks after the operation. The sub-cellular structure, blood-brain-barrier (BBB) and BTB in both groups were observed under electron microscope. Results Apoptosis in different phases and necrosis could be observed in some C6 glioma cells.Swelling occurred on the ultrastructure of cellular organs such as mitochondria and endoplasmic reticulum in most of the cells.Damage to the BTB, reduction of the number of cellular organs in endothelial cells of the capillary blood vessels, stretch of the tight junction, and enlargement of the gaps between endothelial cells were also seen in the experiment group. Meanwhile,limited impact on the normal sub-cellular structures and BBB was observed. Conclusion PDT could induce apoptosis and necrosis of C6 glioma cells due to the damage to the ultrastructure of mitochondria and endoplasmic reticulum. The weakened function of C6 glioma BTB initiated by PDT makes it possible to perform a combined therapy of PDT and chemotherapy for glioma.

  18. 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...

  19. Bioluminescence-activated deep-tissue photodynamic therapy of cancer.

    Science.gov (United States)

    Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

    2015-01-01

    Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.

  20. 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.

  1. Predicting photodynamic therapy efficacy with photoacoustic imaging (Conference Presentation)

    Science.gov (United States)

    Mallidi, Srivalleesha; Mai, Zhiming; Khan, Amjad P.; Hasan, Tayyaba

    2016-03-01

    Photodynamic therapy (PDT) is a photochemistry based cytotoxic technique that imparts cellular damage via excitation of a photosensitizer with drug-specific wavelength of light. The dose at the treatment site for type II PDT is determined by three factors: photosensitizer (PS) concentration, oxygenation status and delivered light irradiance. Most of the FDA approved photosensitizers in their triplet-excited state generate cytotoxic species by reacting with the ground state oxygen that is available in the surrounding environment. Given the inter- and intra-subject variability in the uptake of the photosensitizer and the distribution of oxygen in the tumor, understanding the interplay between these dose parameters could aid in determining photodynamic therapy efficacy. Previously several studies have discussed the interplay between the dose parameters using shown point measurements and 2D imaging systems. Using various subcutaneous and orthotopic mouse models we will demonstrate the utility of a non-invasive non-ionizing photoacoustic imaging modality to determine efficacy and predict treatment response in Benzoporphyrin derivative (BPD) or Aminolevulinic acid (ALA) based PDT. We further compare the predictive capability of photoacoustic imaging with the more predominantly used fluorescence imaging and immunohistochemistry techniques.

  2. Measurement of intracellular oxygen concentration during photodynamic therapy in vitro.

    Science.gov (United States)

    Weston, Mark A; Patterson, Michael S

    2014-01-01

    A technique is introduced that monitors the depletion of intracellular ground state oxygen concentration ([(3)O(2)]) during photodynamic therapy of Mat-LyLu cell monolayers and cell suspensions. The photosensitizer Pd(II) meso-tetra(4-carboxyphenyl)porphine (PdT790) is used to manipulate and indicate intracellular [(3)O(2)] in both of the in vitro models. The Stern-Volmer relationship for PdT790 phosphorescence was characterized in suspensions by flowing nitrogen over the suspension while short pulses of 405 nm light were used to excite the sensitizer. The bleaching of sensitizer and the oxygen consumption rate were also measured during continuous exposure of the cell suspension to the 405 nm laser. Photodynamic therapy (PDT) was conducted in both cell suspensions and in cell monolayers under different treatment conditions while the phosphorescence signal was acquired. The intracellular [(3)O(2)] during PDT was calculated by using the measured Stern-Volmer relationship and correcting for sensitizer photobleaching. In addition, the amount of oxygen that was consumed during the treatments was calculated. It was found that even at large oxygen consumption rates, cells remain well oxygenated during PDT of cell suspensions. For monolayer treatments, it was found that intracellular [(3)O(2)] is rapidly depleted over the course of PDT.

  3. Autologous bone marrow transplantation by photodynamic therapy

    Science.gov (United States)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  4. Indocyanine green-mediated photodynamic therapy on glioblastoma cells in vitro

    OpenAIRE

    AK, Ayşe; Kaya, Özgür; Turgut Coşan, Didem; Gülsoy, Murat

    2015-01-01

    Photodynamic therapy (PDT) is an alternative therapy which is administered with non-toxic drugs, called photosensitizers (PSs), along with irradiation at a specific wavelength of light to damage tumor cells. Different wavelengths of light sources and photosensitizers have been investigated in treatment of many cancer types. In this study, we investigated whether photodynamic therapy using indocyanine green (ICG), also a cyanine dye used in medical diagnostics, can be used to inhibit cell prol...

  5. 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.

  6. Evaluation of quantum dots for photodynamic therapy (Invited Paper)

    Science.gov (United States)

    Dayal, Smita; Krolicki, Robert; Burda, Clemens

    2005-04-01

    Photodynamic therapy (PDT) is an emerging therapy for cancer treatment that shows the greater selectivity towards the malignant cells. Semiconductor nanoparticles are a novel class of photosensitizers with properties that are not easily available with conventional PDT reagents. Their potential properties such as improved luminescence, resistance to photobleaching, and the possibility to modify the surface chemically make them suitable candidates for PDT. In this report, we discuss the synthesis of ternary CdSe1-x Tex nanoparticles along with well known CdSe QDs and their potential in generating the singlet oxygen state by Foerster Resonance Energy Transfer (FRET) to a PDT reagent or by direct triplet-triplet energy transfer to molecular oxygen.

  7. Affordance

    DEFF Research Database (Denmark)

    Olesen, Mogens

    2016-01-01

    This entry presents the concept of affordances as part of an ecological approach to understanding how agents interact with objects in their environment. It examines some of the central developments of the concept, from J. J. Gibson’s original definition within psychology and Donald Norman’s design...

  8. 5-Amino-4-oxopentanoic acid photodynamic diagnosis guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    XIAO Hong; LIAO Qiong; CHENG Ming; LI Fei; XIE Bing; LI Mei; FENG Hua

    2009-01-01

    Background Complete tumour resection is important for improving the prognosis of brain tumour patients. However,extensive resection remains controversial because the tumour margin is difficult to be distinguished from surrounding brain tissue. It has been established that 5-amino-4-oxopentanoic acid (5-aminolevulinic acid, ALA) can be used as a photodynamic diagnostic marker and a photosensitizer for photodynamic therapy in surgical treatment of brain tumours. We investigated the efficacy of ALA photodynamically guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model.Methods Eighty New Zealand rabbits implanted with VX2 brain tumours were randomly assigned to five groups: control, conventional white light microsurgery, a photodynamic therapy group, a photodynamically guided microsurgery group and a group in which guided microsurgery was followed by photodynamic therapy. The VX2 tumour was resected under a surgical microscope. The tumour resection was confirmed with histological analysis. All animals were examined with MRI for presence of any residual tumour tissue. The survival time of each rabbit was recorded.Results All treatment groups showed a significantly extended survival time compared with the control group.Photodynamically guided microsurgery combined with photodynamic therapy significantly prolonged survival time, compared with guided microsurgery alone. MRI and the autopsy results confirmed removal of most of the tumours.Conclusions Our results suggest that photodynamically guided surgery and photodynamic therapy significantly reduce or delay local recurrence, increase the effectiveness of radical resection and prolong the survival time of tumour bearing rabbits, Their combination has the potential to be used as a rapid and highly effective treatment of metastatic brain tumours.

  9. Photodynamic therapy of human tubulo-villous adenomas

    Science.gov (United States)

    Warloe, Trond; Peng, Qian; Heyerdahl, Helen; Waehre, Hakon; Moan, Johan; Steen, Harald B.; Giercksky, Karl-Erik

    1995-01-01

    Nine selected patients with rectal tubulo-villous adenomas were treated with Photofrin- or aminolevulinic acid (ALA)-based photodynamic therapy (PDT) after the main bulk of the primary tumors had been endoscopically resected. The distribution patterns of Photofrin and ALA-induced porphyrins in the adenomas and surrounding normal tissues were studied by means of microscopic fluorescence photometry. Nine patients were treated in a total of 14 PDT sessions. Photofrin and ALA were used in 5 and 9 sessions, respectively. The tumors in all 5 Photofrin-based PDT sessions demonstrated complete regression. However, they all recurred 4 - 20 months after PDT. Four of 9 ALA-based PDT sessions achieved complete regression and so far no recurrence of these tumors has been found, although the follow-up is only 3 - 10 months. Two of the cases of partial response were given a second ALA-based PDT and both of them obtained complete response. The microscopic fluorescence photometry of the biopsies taken from the tumor and surrounding normal tissues after administration of either Photofrin or ALA showed that there was a strong fluorescence of Photofrin in the vascular stroma of the tumor and normal tissues, whereas ALA-induced porphyrins were mainly distributed in the glandular neoplastic cells. The correlation between the distribution of Photofrin and ALA-induced porphyrins in the adenomas and their photodynamic effects is discussed.

  10. Photosensitizer nanocarriers modeling for photodynamic therapy applied to dermatological diseases

    Science.gov (United States)

    Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.

    2011-02-01

    Photodynamic Therapy involves the therapeutic use of photosensitizers in combination with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell death. This technique has become widely used in medicine to treat tumors and other nonmalignant diseases. However, there are several factors related to illumination or the photosensitizer that limit an optimal treatment outcome. The use of nanoparticles (NP) for PDT has been proposed as a solution to current shortcomings. In this way, there are NPs that act as carriers for photosensitizers, NPs that absorb the light and transfer the energy to the photosensitizer and NPs that are themselves photodynamically active. In dermatology, the use of topical photosensitizers produces a time dependent inhomogeneous distribution within the tumor, where the stratum corneum is the main barrier to the diffusion of the photosensitizer to the deeper layers of skin. This produces an insufficient photosensitizer accumulation in tumor tissues and therefore, a low therapeutic efficiency in the case of deep lesions. This work focuses in the use of NPs as photosensitizer carriers to improve the actual topical drug distribution in malignant skin tissues. We present a mathematical model of PS distribution in tumor tissue using NPs that takes into account parameters related to nanoparticles binding. Once the concentration profile of NPs into tissue is obtained, we use a photochemical model which allows us to calculate the temporal evolution of reactive oxygen species according to PS distribution calculated previously from NPs profile.

  11. ALA-Butyrate prodrugs for Photo-Dynamic Therapy

    Science.gov (United States)

    Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

    2010-05-01

    The use of 5-aminolevulinic acid (ALA) administration has led to many applications of photodynamic therapy (PDT) in cancer. However, the hydrophilic nature of ALA limits its ability to penetrate the cells and tissues, and therefore the need for ALA derivatives became an urgent research target. In this study we investigated the activity of novel multifunctional acyloxyalkyl ester prodrugs of ALA that upon metabolic hydrolysis release active components such as, formaldehyde, and the histone deacetylase inhibitory moiety, butyric acid. Evaluation of these prodrugs under photo-irradiation conditions showed that butyryloxyethyl 5-amino-4-oxopentanoate (ALA-BAC) generated the most efficient photodynamic destruction compared to ALA. ALA-BAC stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells which resulted in generation of intracellular ROS, reduction of mitochondrial activity, leading to apoptotic and necrotic death of the cells. The apoptotic cell death induced by ALA / ALA-BAC followed by PDT equally activate intrinsic and extrinsic apoptotic signals and both pathways may occur simultaneously. The main advantage of ALA-BAC over ALA stems from its ability to induce photo-damage at a significantly lower dose than ALA.

  12. 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.

  13. Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green

    OpenAIRE

    Sawa, M; Awazu, K; Takahashi, T.; Sakaguchi, H; Horiike, H.; Ohji, M; Tano, Y

    2004-01-01

    Backgrounds/aims: To evaluate treatment with high peak power pulse energy by femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800 nm wavelength for corneal neovascularisation using photodynamic therapy (PDT) mediated by indocyanine green (ICG).

  14. An ethylene-glycol decorated ruthenium(ii) complex for two-photon photodynamic therapy.

    Science.gov (United States)

    Boca, Sanda C; Four, Mickaël; Bonne, Adeline; van der Sanden, Boudewijn; Astilean, Simion; Baldeck, Patrice L; Lemercier, Gilles

    2009-08-14

    A novel water-soluble Ru(ii) complex has been prepared, which represents a promising new class of selective two-photon sensitizers for use in photodynamic therapy within a confined space. PMID:19617993

  15. mTHPC Mediated, Systemic Photodynamic Therapy (PDT) for Nonmelanoma Skin Cancers : Case and Literature Review

    NARCIS (Netherlands)

    Horlings, Rudolf K.; Terra, Jorrit B.; Witjes, Max J. H.

    2015-01-01

    Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multi

  16. 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.

  17. 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.

  18. Photodynamic Therapy for Non-Melanoma Skin Cancers

    Directory of Open Access Journals (Sweden)

    Diana K. Cohen

    2016-10-01

    Full Text Available Non‐melanoma skin cancer (NMSC is traditionally treated with surgical excision. Nonsurgical methods such as cryotherapy and topical chemotherapeutics, amongst other treatments, are other options. Actinic keratosis (AKs are considered precancerous lesions that eventually may progress to squamous cell carcinoma (SCC. Photodynamic therapy (PDT offers an effective treatment for AKs, and is also effective for superficial basal cell carcinoma (BCC. Nodular BCC and Bowen’s disease (SCC in situ have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes. Methylaminolevulinate (MAL PDT is a more effective treatment option than 5‐aminolevulinic acid (ALA PDT for nodular BCC. Several studies have shown that PDT results in superior cosmetic outcomes compared to surgical treatment. PDT is overall well‐tolerated, with pain being the most common side effect.

  19. Mitochondria-involved apoptosis induced by MPPa mediated photodynamic therapy

    International Nuclear Information System (INIS)

    Numerous new photosensitizers are now in various stages of trials demonstrating the broad applicability of Photodynamic therapy (PDT). However, only a handful of photosensitizers have received regulatory approval. Lack of effective photosensitizers has become a major limit for extensive application of PDT. Our previous study showed MPPa to be a good photosensitizer candidature, MPPa-PDT can lead PC-3M cell line to death mainly via apoptotic way both in vitro and in vivo, and part of the mechanism was investigated. Mitochondria may play a key role in the process, in order to further elucidate the mechanism, we investigated the level of ROS, GSH, NO, Ca2+, mitochondrial membrane potential, as well as cytochrome C. All in all, ROS production, depletion of GSH, and the activation of ROS downstream, such as mitochondria depolarization, cytochrome C release, were detected in our study. The results provide a mechanism by which oxidative stress provokes apoptosis of PC-3M cells

  20. Colonic cancer cell polyamine synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    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

  1. 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

  2. A novel diode laser system for photodynamic therapy

    DEFF Research Database (Denmark)

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

    2001-01-01

    In this paper a novel diode laser system for photodynamic therapy is demonstrated. The system is based on linear spatial filtering and optical phase conjugate feedback from a photorefractive BaTiO3 crystal. The spatial coherence properties of the diode laser are significantly improved. The system...... provides an almost diffraction limited output which is efficiently coupled into a 50 mum core diameter fiber. The optical power transmitted through the fiber is increased by a factor of six when the feedback is applied to the diode laser. 85 percent of the power from the freely running laser diode...... is extracted in a high-quality beam and 80 percent of the output power is extracted through the fiber. The power transmitted through tile fiber scales linearly with the power of the laser diode. which means that a laser diode emitting 1.7 W multi-mode radiation would provide 1 W of optical power through a 50...

  3. Inactivation of bovine immunodeficiency virus by photodynamic therapy with HMME

    Institute of Scientific and Technical Information of China (English)

    Huijuan Yin; Yingxin Li; Zhaohui Zou; Wentao Qiao; Xue Yao; Yang Su; Hongyan Guo

    2008-01-01

    To investigate the effect of photodynamic therapy (PDT) with hematoporphrin monomethyl ether (HMME) on bovine immunodeficiency virus (BIV) can provide the basis theory for photoinactivation of human immunodeficiency virus (HIV). To assess the protection of HMME-PDT on the cell line Cf2Th infected with BIVR29 by 3-(4,5)-dimethylthiahiazol-2-yl-3,5-di-phenytetrazolium bromide (MTT) with power density of 5 and 25 mW/cm2 and energy density from 0.6 to 3 J/cm. To observe the inhibition of membrane fusion using a new reporter cell line BIVE by fluorescence microscope. HMME-PDT has significant protectant effects on Cf2Th-BIVR29 with both power densities, especially in the group of high power density. Fluorescent microscope shows that there is no significant difference between the group of PDT and control, which means PDT could not inhibit the BIV-mediated membrane fusion.

  4. Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles

    Science.gov (United States)

    Kishen, Anil; George, Saji

    2013-02-01

    In this study, we tested the hypothesis that a microbubble containing photosensitizer when activated with light would enable comprehensive disinfection of bacterial biofilms in infected root dentin by antimicrobial photodynamic therapy (APDT). Experiments were conducted in two stages. In the stage-1, microbubble containing photosensitizing formulation was tested for its photochemical properties. In the stage-2, the efficacy of microbubble containing photosensitizing formulation was tested on in vitro infected root canal model, developed with monospecies biofilm models of Enterococcus faecalis on root dentin substrate. The findings from this study showed that the microbubble containing photosensitizing formulation was overall the most effective formulation for photooxidation, generation of singlet oxygen, and in disinfecting the biofilm bacteria in the infected root canal model. This modified photosensitizing formulation will have potential advantages in eliminating bacterial biofilms from infected root dentin.

  5. Nanosized ZSM-5 will improve photodynamic therapy using Methylene blue.

    Science.gov (United States)

    Kariminezhad, H; Habibi, M; Mirzababayi, N

    2015-07-01

    Nowadays, nanotechnology is growing to improve Photodynamic Therapy and reduce its side effects. In this research, the synthesized co-polymeric Zeolite Secony Mobile-5 (ZSM-5) was employed to modify Methylene Blue (MB) for these reasons. UV-Visible, FTIR, XRD analysis and SEM images were used to investigate obtained nanostructure. The crystal size for these nanostructures were determined 75 nm and maximum adsorption capacity of MB in the nanostructure was estimated 111 (mg g(-1)). Also, the role of Polyethylene Glycol (PEG) was studied as a capable non-toxic polymeric coating to overcome biological barriers. Moreover, potential of singlet oxygen production of the synthesized nanostructure was compared with MB and ZSM-5 nanoparticles control samples. Synthesized nanodrugs show impressive light induced singlet oxygen production efficiency. PMID:25900556

  6. TOPICAL REVIEW: The physics, biophysics and technology of photodynamic therapy

    Science.gov (United States)

    Wilson, Brian C.; Patterson, Michael S.

    2008-05-01

    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.

  7. Effects of verteporfin-mediated photodynamic therapy on endothelial cells

    Science.gov (United States)

    Kraus, Daniel; Chen, Bin

    2015-03-01

    Photodynamic therapy (PDT) is a treatment modality in which cytotoxic reactive oxygen species are generated from oxygen and other biological molecules when a photosensitizer is activated by light. PDT has been approved for the treatment of cancers and age-related macular degeneration (AMD) due to its effectiveness in cell killing and manageable normal tissue complications. In this study, we characterized the effects of verteporfin-PDT on SVEC mouse endothelial cells and determined its underlying cell death mechanisms. We found that verteporfin was primarily localized in mitochondria and endoplasmic reticulum (ER) in SVEC cells. Light treatment of photosensitized SVEC cells induced a rapid onset of cell apoptosis. In addition to significant structural damages to mitochondria and ER, verteporfin-PDT caused substantial degradation of ER signaling molecules, suggesting ER stress. These results demonstrate that verteporfin-PDT triggered SVEC cell apoptosis by both mitochondrial and ER stress pathways. Results from this study may lead to novel therapeutic approaches to enhance PDT outcome.

  8. Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity

    OpenAIRE

    Lamberti, María Julia; Vittar, Natalia Belén Rumie; RIVAROLA, VIVIANA ALICIA

    2014-01-01

    Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article ...

  9. The results of the treatment of various morphological types of ENT skin cancer by photodynamic therapy

    OpenAIRE

    Volgin V.N.; Stranadko E.F.; Kagoyants R.V.

    2014-01-01

    This article discusses one of the urgent problems of modern oncology — the question of treatment of skin cancer (SC). The experience of the new promising method of photodynamic therapy (PDT) in the treatment of patients with primary and recurrent skin cancer. Aim: to evaluate the effectiveness of photodynamic therapy (PDT) in the treatment of patients with primary and recurrent skin cancer (SC). Materials. The Main Military Clinical Hospital SC treatment of upper respiratory tract with PDT pe...

  10. Methylaminolaevulinic acid photodynamic therapy in the treatment of erythroplasia of Queyrat

    OpenAIRE

    Feldmeyer, L; Krausz-Enderlin, V; Töndury, B; Hafner, J.; French, L.E.; Hofbauer, G.F.L.

    2011-01-01

    BACKGROUND: Erythroplasia of Queyrat (EQ) is an intra-epithelial carcinoma of the penis. Progression to invasive carcinoma may occur. Its cause is unknown but some evidence suggests infection with human papillomavirus in the pathogenesis of EQ; however, recent data do not confirm this. Therapy is difficult and associated with important recurrence rates. Photodynamic therapy (PDT) employs a photosensitizer excited by visible light. The resulting photodynamic reaction selectively destroys atyp...

  11. 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.......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....

  12. Improved results of treatment of purulent wounds with complex use of photodynamic therapy and CO2 laser in the experiment

    OpenAIRE

    TESHAEV OKTYABR RUHULLAEVICH; MURODOV ALIJON SALIMOVICH; SADYKOV RАSUL RUSTAMOVICH; HAMDAMOV BAKHTIYOR ZARIPOVICH

    2016-01-01

    The aim of research was the evaluation of the effectiveness of photodynamic therapy and CO2 laser destructive purulent wounds of soft tissues in the experiment. Photodynamic therapy is a very effective non-invasive and gentle treatment of purulent wounds and serve as justification for the use of the method of photodynamic therapy in clinical practice for the treatment of acute local inflammatory processes combined with CO2 laser and traditional treatments. These laboratory, thermometry, morph...

  13. Exploiting apoptosis in photodynamic therapy: is it possible?

    Science.gov (United States)

    Rendon, Cesar A.; Lilge, Lothar D.

    2003-06-01

    Glioblastoma Multiforme is the most common form of malignant brain tumors and accounts for approximately 25% of all primary brain tumors. Only 5% of these patients survive longer than 2 years. The standard form of treatment is radiation therapy and surgery if the site is accessible. Different forms of adjuvant chemotherapy have been largely proven unsuccessful. Another form of adjuvant therapy, Photodynamic Therapy (PDT), has undergone preliminary trials showing some promising results but at the cost of increased side effects like rise in intracranial blood pressure and neurological deficiency. Apoptotic cell kill used as a biological treatment endpoint can possibly ameliorate these side effects. This study evaluates the significance of apoptotic cell death in the 9L rat gliosarcoma using the aminolevulinic acid (ALA) induced endogenous photosensitizer Protophorphyrin IX (PpIX). A strong influence of drug incubation time with cell kill was observed. The percentage of apoptotic cell death was less than 10% for 2 and 4 hours incubation times and irradiation times ensuring up to 70 and 80% cell kill respectively. Accumulation of PpIX in the mitochondria and cytoplasm was quantified by confocal fluorescence microscopy showing a linear relationship of PpIX fluorescence with concentration. The possibility of an in vitro threshold in the PDT dose is discussed, above which cell repair mechanisms may become exhausted. In conclusion for the range of parameters investigated, apoptotic cell kill may be hard to exploit therapeutically in this tumor model.

  14. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

    Science.gov (United States)

    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  15. Photosensitizer-loaded gold nanorods for near infrared photodynamic and photothermal cancer therapy.

    Science.gov (United States)

    Bhana, Saheel; O'Connor, Ryan; Johnson, Jermaine; Ziebarth, Jesse D; Henderson, Luke; Huang, Xiaohua

    2016-05-01

    Despite the advancement of photodynamic therapy and photothermal therapy, the ability to form compact nanocomplex for combined photodynamic and photothermal cancer therapy under a single near infrared irradiation remains limited. In this work, we prepared an integrated sub-100 nm nanosystem for simultaneous near infrared photodynamic and photothermal cancer therapy. The nanosystem was formed by adsorption of silicon 2,3-naphthalocyanine dihydroxide onto gold nanorod followed by covalent stabilization with alkylthiol linked polyethylene glycol. The effects of alkylthiol chain length on drug loading, release and cell killing efficacy were examined using 6-mercaptohexanoic acid, 11-mercaptoundecanoic acid and 16-mercaptohexadecanoic acid. We found that the loading efficiency of silicon 2,3-naphthalocyanine dihydroxide increased and the release rate decreased with the increase of the alkylthiol chain length. We demonstrated that the combined near infrared photodynamic and photothermal therapy using the silicon 2,3-naphthalocyanine dihydroxide-loaded gold nanorods exhibit superior efficacy in cancer cell destruction as compared to photodynamic therapy and photothermal therapy alone. The nanocomplex stabilized with 16-mercaptohexadecanoic acid linked polyethylene glycol provided highest cell killing efficiency as compared to those stabilized with the other two stabilizers under low drug dose. This new nanosystem has potential to completely eradicate tumors via noninvasive phototherapy, preventing tumor reoccurrence and metastasis.

  16. Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic therapy

    Science.gov (United States)

    Xu, Yu; Shi, Zhenzhi; Zhang, Ling'e.; Brown, Eric Michael Bratsolias; Wu, Aiguo

    2016-06-01

    Layered bismuth oxyhalide nanomaterials have received much more interest as promising photocatalysts because of their unique layered structures and high photocatalytic performance, which can be used as potential inorganic photosensitizers in tumor photodynamic therapy (PDT). In recent years, photocatalytic materials have been widely used in PDT and photothermal therapy (PTT) as inorganic photosensitizers. This investigation focuses on applying layered bismuth oxyhalide nanomaterials toward cancer PDT, an application that has never been reported so far. The results of our study indicate that the efficiency of UV-triggered PDT was highest when using BiOCl nanoplates followed by BiOCl nanosheets, and then TiO2. Of particular interest is the fact that layered BiOCl nanomaterials showed excellent PDT effects under low nanomaterial dose (20 μg mL-1) and low UV dose (2.2 mW cm-2 for 10 min) conditions, while TiO2 showed almost no therapeutic effect under the same parameters. BiOCl nanoplates and nanosheets have shown excellent performance and an extensive range of applications in PDT.

  17. Photodynamic therapy for pancreatic and biliary tract carcinoma

    Science.gov (United States)

    Pereira, Stephen P.

    2009-02-01

    Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.

  18. Photonanomedicine: a convergence of photodynamic therapy and nanotechnology

    Science.gov (United States)

    Obaid, Girgis; Broekgaarden, Mans; Bulin, Anne-Laure; Huang, Huang-Chiao; Kuriakose, Jerrin; Liu, Joyce; Hasan, Tayyaba

    2016-06-01

    As clinical nanomedicine has emerged over the past two decades, phototherapeutic advancements using nanotechnology have also evolved and impacted disease management. Because of unique features attributable to the light activation process of molecules, photonanomedicine (PNM) holds significant promise as a personalized, image-guided therapeutic approach for cancer and non-cancer pathologies. The convergence of advanced photochemical therapies such as photodynamic therapy (PDT) and imaging modalities with sophisticated nanotechnologies is enabling the ongoing evolution of fundamental PNM formulations, such as Visudyne®, into progressive forward-looking platforms that integrate theranostics (therapeutics and diagnostics), molecular selectivity, the spatiotemporally controlled release of synergistic therapeutics, along with regulated, sustained drug dosing. Considering that the envisioned goal of these integrated platforms is proving to be realistic, this review will discuss how PNM has evolved over the years as a preclinical and clinical amalgamation of nanotechnology with PDT. The encouraging investigations that emphasize the potent synergy between photochemistry and nanotherapeutics, in addition to the growing realization of the value of these multi-faceted theranostic nanoplatforms, will assist in driving PNM formulations into mainstream oncological clinical practice as a necessary tool in the medical armamentarium.

  19. Cell Death Pathways in Photodynamic Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    Michael R. Hamblin

    2011-06-01

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

  20. 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.

  1. Cell Death Pathways in Photodynamic Therapy of Cancer

    International Nuclear Information System (INIS)

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

  2. Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

    2008-02-01

    Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

  3. Photodynamic Therapy As a Promising Method Used in the Treatment of Oral Diseases.

    Science.gov (United States)

    Prażmo, Ewa J; Kwaśny, Mirosław; Łapiński, Mariusz; Mielczarek, Agnieszka

    2016-01-01

    Photodynamic therapy (PDT) consists of three elements: photosensitizer, light and oxygen. The photosensitizer has the property of selective accumulation in abnormal or infected tissues without causing any damage to the healthy cells. This innovative therapeutic method has already been successfully adapted in many fields of medicine, e.g. dermatology, gynecology, urology and cancer therapy. Dentistry is also beginning to incorporate photodisinfection for treatment of the oral cavity. The antibacterial and fungicidal properties of the photosensitizer have been used to achieve better results in root canal treatment, periodontal therapy and the eradication of candidiasis in prosthodontics. The aim of this article is to discuss the effectiveness of photodynamic methods in the diagnosis and therapy of selected oral diseases. Scientific data and published papers regarding the antibacterial properties of PDT will be subjected to analysis. Photodynamic therapy will be discussed as an alternative treatment protocol in oncology, endodontics, periodontology and other fields of dentistry. PMID:27629857

  4. Interstitial 5-ALA photodynamic therapy and glioblastoma: preclinical model development and preliminary results.

    OpenAIRE

    TETARD, MARIE-CHARLOTTE; Vermandel, Maximilien; Leroy, Henri-Arthur; Leroux, Bertrand; Maurage, Claude-Alain; Lejeune, Jean-Paul; Mordon, Serge; Reyns, Nicolas

    2015-01-01

    AbstractOBJECTIVE: Photodynamic therapy (PDT) has become a well-established modality for the treatment of many cancers. Photodynamic eradication of tumor cells depends on the presence of a photosensitizer, oxygen and light. However, oxygen depletion during PDT is a well known problem. Modulation of light delivery could address this issue by counteracting tumor hypoxia, thereby improving tumor cell killing. This preclinical study was designed to validate an animal model incorporating 5-aminola...

  5. LED Light Source for in vitro Study of Photosensitizing Agents for Photodynamic Therapy

    OpenAIRE

    Shilyagina N.Y.; Plekhanov V.I.; Shkunov I.V.; Shilyagin P.А.; Dubasova L.V.; Brilkina А.А.; Sokolova E.A.; Turchin I.V.; Balalaeva I.V.

    2014-01-01

    The aim of the investigation was to develop a LED light source providing a homogeneous light distribution in 96-well plates and allowing an independent irradiation of individual wells, as well as its experimental testing in in vitro study of photosensitizers for photodynamic therapy. Materials and Methods. The experiments were carried out on human cell lines of epidermoid carcinoma А-431 and human bladder carcinoma Т24. Two photosensitizers for fluorescence diagnostics and photodynamic th...

  6. Photodynamic therapy of non-melanoma skin cancers

    Science.gov (United States)

    Ikram, M.; Khan, R. U.; Firdous, S.; Atif, M.; Nawaz, M.

    2011-02-01

    In this prospective study duly approved from Institutional Ethics Review Committee for research in medicine, PAEC General Hospital Islamabad, Pakistan, we investigate the efficacy, safety and tolerability along with cosmetic outcome of topical 5-aminolaevulinic acid photodynamic therapy for superficial nonmelanoma skin cancers (NMSCs) and their precursors. Patients with Histological diagnosis of NMSCs and their precursors were assessed for PDT, after photographic documentation of the lesions and written consent, underwent two (2) sessions of PDT in one month (4 weeks) according to standard protocol. A freshly prepared 20% 5-ALA in Unguentum base was applied under occlusive dressing for 4-6 h as Drug Light Interval (DLI) and irradiated with light of 630 nm wavelength from a diode laser at standard dose of 90 J/cm2. Approximately 11% patients reported pain during treatment which was managed in different simple ways. In our study we regularly followed up the patients for gross as well as histopathological response and recurrence free periods during median follow-up of 24 months. Regarding Basal cell carcinomas complete response was observed in 86.2% (25/29), partial response in 10.3% (3/29) and recurrence during first year in 3.5% (1/29) lesions. All the lesions which showed partial response or recurrence were nBCCs. Regarding Actinic Keratosis complete response was observed in 95.3% (20/21), partial response in 4.7% (1/21) while Bowen's disease showed 100% (2/2) results. 81.8% (9/11) Squamous Cell Carcinomas showed complete, 9% (1/11) partial response and 9% (1/11) presented with recurrence after 3 months. We observed excellent and good cosmetic results along with tumor clearance in our study. Treatment sessions were well tolerated with high level of patient's satisfaction and only minor side effects of pain during treatment sessions and inflammatory changes post photodynamic therapy were observed. We concluded that 5-ALA PDT is an effective and safe emerging

  7. Treatment of bile duct carcinoma using photodynamic therapy (PDT)

    International Nuclear Information System (INIS)

    Full text: Biliary papillomatosis, is a rare, benign tumour characterised by extensive mucosal involvement of the bile duct with carcinoma in 30% of cases. Treatment has been largely limited to surgical resection and is often accompanied by tumour recurrence. Photodynamic therapy (PDT) was used to treat a 64 year old man with mucous-secreting papillomatosis of the common bile hepatic duct which presented with obstructive jaundice and recurrent cholangitis. The successful use of PDT in treating a case of cholangiocarcinoma and the treatment of similar colonic villous tumours encourage the use of PDT in this patient. Porfimer Sodium (Photofrin), 2 mg/kg was given intravenously 64 hours prior to light exposure. A Spectra Physics argon-ion pumped dye laser was used to provide 50 mW of 630 nm wavelength light at a 3 cm long diffusing tip attached to a 3 m optical fibre. A power density of approximately 15 mW.cm-2 was provided at the tissue surface under illumination at a radial distance of approximately 1.8 mm from the diffusing tip. The dose was designed to give a necrosis depth of 3 mm. A transparent 3.6 mm outer diameter catheter was placed in the duct using fluoroscopy and the fibre and diffusing tip then manoeuvred into position. The transparent catheter was left in place during the treatment and forced a minimum inner diameter on the duct of 3.6 mm and also helped to centre the diffuser within the duct. Repeat endoscopy, 48 hours after treatment revealed little duct mucous; necrosed tissue was removed with a balloon catheter with significant increase in size of the duct lumen. Since then, the patient's bilirubin has remained normal. Repeat endoscopic cholangiography one month later has shown no diminution in the diameter of the bile duct. The use of Photodynamic Therapy in the biliary tree using endoscopic retrograde placement of light source is feasible and the results in this patient encourage a trial of its use in operable bile duct carcinoma

  8. Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

    OpenAIRE

    Cabete, J; Rafael, M; Cravo, M; Moura, C.; Sachse, F; Pecegueiro, M

    2015-01-01

    BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynam...

  9. Long-term recurrence of nonmelanoma skin cancer after topical methylaminolevulinate photodynamic therapy in a dermato-oncology department*

    OpenAIRE

    Cabete, Joana; Rafael, Margarida; Cravo, Mariana; Moura, Cecília; Sachse, Fernanda; Pecegueiro, Manuela

    2015-01-01

    BACKGROUND Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therap...

  10. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    Science.gov (United States)

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  11. Prevention of Distant Lung Metastasis After Photodynamic Therapy Application in a Breast Cancer Tumor Model.

    Science.gov (United States)

    Longo, João Paulo Figueiró; Muehlmann, Luis Alexandre; Miranda-Vilela, Ana Luisa; Portilho, Flávia Arruda; de Souza, Ludmilla Regina; Silva, Jaqueline Rodrigues; Lacava, Zulmira Guerrero Marques; Bocca, Anamelia Lorenzetti; Chaves, Sacha Braun; Azevedo, Ricardo Bentes

    2016-04-01

    The objective of this study was to investigate the activity of photodynamic therapy mediated by aluminum-chlorophthalocyanine contained in a polymeric nanostructured carrier composed by methyl vinyl ether-co-maleic anhydride (PVM/MA) against local subcutaneous breast cancer tumors and its effects against distant metastasis in a mouse tumor model. In our results, we observed a decrease in breast cancer tumor growth, prevention of distant lung metastases, and a significant increased survival in mice treated with photodynamic therapy. In addition to these results, we observed that tumor-bearing mice without treatment developed a significant extension of liver hematopoiesis that was significantly reduced in mice treated with photodynamic therapy. We hypothesized and showed that this reduction in (1) metastasis and (2) liver hematopoiesis may be related to the systemic activity of immature hematopoietic cells, specifically the myeloid-derived suppressor cells, which were suppressed in mice treated with photodynamic therapy. These cells produce a tolerogenic tumor environment that protects tumor tissues from immunological surveillance. Therefore, we suggest that photodynamic therapy could be employed in combination with other conventional therapies; such as surgery and radiotherapy, to improve the overall survival of patients diagnosed with breast cancer, as observed in our experimental resuIts. PMID:27301195

  12. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine.

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M; Bielawska, Alicja; Separovic, Duska

    2016-09-15

    Acid ceramidase has been identified as a promising target for cancer therapy. One of its most effective inhibitors, LCL521, was examined as adjuvant to photodynamic therapy (PDT) using mouse squamous cell carcinoma SCCVII model of head and neck cancer. Lethal effects of PDT, assessed by colony forming ability of in vitro treated SCCVII cells, were greatly enhanced when combined with 10 µM LCL521 treatment particularly when preceding PDT. When PDT-treated SCCVII cells are used to vaccinate SCCVII tumor-bearing mice (PDT vaccine protocol), adjuvant LCL521 treatment (75 mg/kg) resulted in a marked retardation of tumor growth. This effect can be attributed to the capacity of LCL521 to effectively restrict the activity of two main immunoregulatory cell populations (Tregs and myeloid-derived suppressor cells, MDSCs) that are known to hinder the efficacy of PDT vaccines. The therapeutic benefit with adjuvant LCL521 was also achieved with SCCVII tumors treated with standard PDT when using immunocompetent mice but not with immunodeficient hosts. The interaction of LCL521 with PDT-based antitumor mechanisms is dominated by immune system contribution that includes overriding the effects of immunoregulatory cells, but could also include a tacit contribution from boosting direct tumor cell kill. PMID:27136745

  13. 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....... OBJECTIVES: To establish consensus recommendations for the use of daylight photodynamic therapy (DL-PDT) using topical methyl aminolaevulinate (MAL) in European patients with AKs. METHODS: The DL-PDT consensus recommendations were developed on behalf of the European Society for Photodynamic Therapy...... in Dermatology and comprised of 10 dermatologists from different European countries with experience in how to treat AK patients with PDT. Consensus was developed based on literature review and experience of the experts in the treatment of AK using DL-PDT. RESULTS: The recommendations arising from this panel...

  14. Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy.

    Science.gov (United States)

    Bebes, Attila; Nagy, Tünde; Bata-Csörgo, Zsuzsanna; Kemény, Lajos; Dobozy, Attila; Széll, Márta

    2011-11-01

    Photodynamic therapy is based on the selective accumulation of a photosensitizer in tumors, followed by destruction of the target tissue by a light source. Protoporphyrin IX, a well-known photosensitizer, was recently reported as an endogenous substrate for the multidrug transporter ABCG2. We investigated the role of ABCG2 protein in the porphyrin extrusion ability of keratinocytes, with regard to the impact of the specific inhibition of ABCG2 by a non-toxic fumitremorgin C analog, Ko-134, on photodynamic therapy efficacy. We studied the level of porphyrin accumulation in response to delta-aminolevulinic acid pretreatment in proliferating and highly differentiated HaCaT keratinocytes. An in vitro model of photodynamic therapy on HaCaT cells was established with a therapeutically approved narrow-bandwidth red-light source. The porphyrin extrusion ability of HaCaT cells proved to correlate with their ABCG2 expression which was higher in proliferating cells than in differentiated cells. Moreover, the specific inhibition of ABCG2 by Ko-134 enhanced the sensitivity of keratinocytes to photodynamic therapy in vitro. These results suggest that ABCG2 may serve as a target molecule via which to improve the photodynamic therapy of skin lesions: its inhibition by the non-toxic Ko-134 is a promising therapeutic modality.

  15. Enhanced apoptotic response to photodynamic therapy after bcl-2 transfection.

    Science.gov (United States)

    Kim, H R; Luo, Y; Li, G; Kessel, D

    1999-07-15

    Apoptosis is a cellular death process involving the sequential activation of a series of caspases, endonucleases, and other enzymes. The initiation of apoptosis can be inhibited by overexpression of bcl-2 and certain other members of a related family of proteins. We examined the effects of bcl-2 overexpression on the apoptotic response to photodynamic therapy (PDT), using aluminum phthalocyanine as the photosensitizing agent. In this study, we compared the immortalized human breast epithelial cell line MCF10A with a subline (MCF10A/bcl-2) transfected with the human bcl-2 gene. The latter was approximately 2-fold more sensitive to the phototoxic effects of PDT. At a 50 mJ/cm2 light dose, photodamage to MCF-10A/bcl-2 resulted in a greater loss of the mitochondrial membrane potential (delta(psi)m), enhanced release of mitochondrial cytochrome c, a more rapid and greater activation of caspase-3, and a greater apoptotic response. Western blot analysis revealed that the transfected cell line showed overexpression of both bcl-2 and bax, and that PDT caused selective destruction of bcl-2, leaving bax unaffected. The greater apoptotic response by the transfected line is, therefore, attributed to the higher bax:bcl-2 ratio after photodamage.

  16. An update on photodynamic therapies in the treatment of onychomycosis.

    Science.gov (United States)

    Simmons, B J; Griffith, R D; Falto-Aizpurua, L A; Nouri, K

    2015-07-01

    Onychomycosis is a common fungal infection of the nails that is increasing in prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a therapeutic challenge that can lead to significant reductions in quality of life leading to both physical and psychological consequences. Current treatment modalities are difficult to implement due to the poor penetration of topical treatments to the nail bed, the slow growing nature of nails and the need for prolonged use of topical and/or oral medications. Standard of care medications have cure rates of 63-76% that leads to a high propensity of treatment failures and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and aminolevulinic acid (ALA) have been used as photosensitizers with approximately 630 nm light. These modalities are combined with pre-treatment of urea and/or microabrasion for better penetration. PDT treatments are well tolerated with only mild transient pain, burning and erythema. In addition, significant cure rates for patients who have contraindications to oral medications or failed standard medications can be obtained. With further enhancements in photosensitizer permeability, decreased pre-treatment and photosensitizer incubation times, PDT can be a more efficient and cost-effective in office based treatment for onychomycosis. However, more large-scale randomized control clinical trials are needed to access the efficacy of PDT treatments. PMID:25589056

  17. Fluorescence guided evaluation of photodynamic therapy as acne treatment

    Science.gov (United States)

    Ericson, Marica B.; Horfelt, Camilla; Cheng, Elaine; Larsson, Frida; Larko, Olle; Wennberg, Ann-Marie

    2005-08-01

    Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes it possible to treat acne with PDT. This initial study investigates the possibility of fluorescence imaging as assessment tool in adjunct to PDT of patients with acne. Twenty-four patients with acne on the cheeks have been treated with PDT with and without mALA. Fluorescence images have been obtained before and after treatment. The clinical acne score was assessed as base line before PDT, and at every follow up visit. Additionally the amount of P.acnes was determined. The clinical evaluation showed a general improvement of acne, even though no difference between treatment with and without mALA was observed. By performing texture analysis and multivariate data analsysis on the fluorescence images, the extracted texture features were found to correlate with the corresponding clinical assessment (67%) and amount of P.acnes (72%). The analysis showed that features describing the highly fluorescent pores could be related to the clinical assessment. This result suggests that fluorescence imaging can be used as an objective assessment of acne, but further improvement of the technique is possible, for example by including colour images.

  18. 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). PMID:27246858

  19. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    Science.gov (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  20. 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.

  1. Photodynamic therapy of oral Candida infection in a mouse model.

    Science.gov (United States)

    Freire, Fernanda; Ferraresi, Cleber; Jorge, Antonio Olavo C; Hamblin, Michael R

    2016-06-01

    Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis.

  2. Photodynamic therapy of oral Candida infection in a mouse model.

    Science.gov (United States)

    Freire, Fernanda; Ferraresi, Cleber; Jorge, Antonio Olavo C; Hamblin, Michael R

    2016-06-01

    Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis. PMID:27074245

  3. Intratumor temperature measurements during photodynamic therapy and hyperthermia

    International Nuclear Information System (INIS)

    Using a mammary adeno-carcinoma implanted in C/sub 3/H mice, tumor temperatures during photodynamic therapy (PDT) and hyperthermic treatments were measured. Microthermocouples made from 0.002'' copper-constantan wires were made into a linear array of 3 sensing points, 2 mm apart. These thermocouples were placed inside the tumors during each treatment. Treatments included: 1) Light (no drug) using a xenon arc lamp or an argon ion pumped dye laser, 2) PDT (with Photofrin II) using the same sources of light as above, and 3) Hyperthermia, using a heated water bath. The hyperthermic ''dose'' was 430C for 1 hour, and the light dose was 100 Joules/cm/sup 2/. Combinations of treatments were studied using light, PDT and hyperthermia. The light or PDT were followed 0 or 1 hours later with hyperthermia. Preliminary experimental data shows a difference in tumor temperature for some treatments. This difference is associated with the presence or absence of the photosensitizing drug (Photofrin II). Tumors reach higher temperatures when the drug is present and during PDT treatment. For combined treatments the intratumor temperature during the hyperthermia phase are also higher, than in identical control (hyperthermia alone) studies. Experimental data showing whether this difference is statistically significant and potential reasons for such differences will be presented

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

    International Nuclear Information System (INIS)

    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)

  5. In vitro studies of the antiherpetic effect of photodynamic therapy.

    Science.gov (United States)

    Zverev, V V; Makarov, O V; Khashukoeva, A Z; Svitich, O A; Dobrokhotova, Y E; Markova, E A; Labginov, P A; Khlinova, S A; Shulenina, E A; Gankovskaya, L V

    2016-07-01

    The number of viral infection cases in the Department of Gynecology and Obstetrics has tended to increase over last few years. Viruses form herpesvirus and cytomegalovirus families are associated with an increased risk for recurrent pregnancy loss. Photodynamic therapy (PDT) is a promising new approach to treat viral infections in which viral particles are inactivated. It exhibits great therapeutic potential, particularly among this group of patients. This study examined the use of PDT to treat herpesvirus infection (HVI) using an in vitro model. In this study, we used the Vero сell lineage as a suitable model of HVI, strains of HSV-1 (strain VR-3) and HSV-2 (strain MS) obtained from The National Virus Collection (London, UK), the photosensitizer Fotoditazine (Veta-Grand, Russia), an AFS physiotherapeutic device (Polironic Corporation, Russia). Laser light irradiation and the photosensitizer had different cytotoxic effects on the Vero cell cultures depending on the doses used. The optimal laser light and photosensitizer doses were determined. PDT had an antiviral effect on an in vitro model of HVI in cell culture. PDT has been shown to be effective treatment for HVI in vitro, leading to a reliable decrease of viral titer. PMID:27003896

  6. Photodynamic therapy of condyloma acuminata in pregnant women

    Institute of Scientific and Technical Information of China (English)

    YANG Yu-guang; ZOU Xian-biao; ZHAO Hua; ZHANG Yun-jie; LI Heng-jin

    2012-01-01

    Background Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an emerging technique for the treatment of genital human papillomavirus (HPV)-induced benign and premalignant lesions.We report here in a case series of condyloma acuminata (CA) in pregnancy successfully treated with ALA-PDT.Methods Five pregnant patients with CA received three to four times treatment respectively.Patients were followed up for 6-23 months after treatment.Results The clearance rate of genital warts was 100%.No recurrence was found during the follow-up period.Major adverse events reported were mild erosion,pain,and local edema.All pregnancies resulted in healthy live births without delivery complications.Conclusions PDT with topical ALA seems to be safe and effective in the treatment of CA in pregnancy.It demonstrated high clearance rate of warts,was well-tolerated by patients,and showed no adverse effects on mothers or fetuses.ALA-PDT may be an ideal strategy of treatment for pregnant women with CA.

  7. Cell death mechanisms vary with photodynamic therapy dose and photosensitizer

    Science.gov (United States)

    He, Jin; Oleinick, Nancy L.

    1995-03-01

    Mouse lymphoma L5178Y-R cells respond to photodynamic therapy (PDT) by undergoing rapid apoptosis, which is induced by PDT-activated signal transduction initiating in the damaged cellular membranes. To relate the level of PDT damage and photosensitizer to the mechanism of cell death, apoptosis has been detected by agarose gel electrophoresis of fragmented DNA and quantified by flow cytometry of cells after staining with Hoechst33342 and propidium iodide, a technique which can distinguish between live, apoptotic, and necrotic cells. When the silicon phthalocyanine Pc 4 or Pc 12 served as photosensitizer, lethal doses (as defined by clonogenic assay) of PDT induced apoptosis in essentially all cells, whereas supralethal doses prevented the characteristic degradation of DNA into oligonucleosomal fragments. In contrast with aluminum phthalocyanine (AlPc) cells died by apoptosis after all doses studied. It appears that high PDT doses with Pc 4 or Pc 12 damage enzymes needed to carry out the program of apoptosis; the absence of this effect with AlPc suggests either a different intracellular location or different photocytotoxic mechanism for the two photosensitizers.

  8. Application of long-circulating liposomes to cancer photodynamic therapy.

    Science.gov (United States)

    Oku, N; Saito, N; Namba, Y; Tsukada, H; Dolphin, D; Okada, S

    1997-06-01

    Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT. PMID:9212988

  9. A robotic multi-channel platform for interstitial photodynamic therapy

    Science.gov (United States)

    Sharikova, Anna V.; Finlay, Jarod C.; Dimofte, Andreea; Zhu, Timothy C.

    2013-03-01

    A custom-made robotic multichannel platform for interstitial photodynamic therapy (PDT) and diffuse optical tomography (DOT) was developed and tested in a phantom experiment. The system, which was compatible with the operating room (OR) environment, had 16 channels for independent positioning of light sources and/or isotropic detectors in separate catheters. Each channel's motor had an optical encoder for position feedback, with resolution of 0.05 mm, and a maximum speed of 5 cm/s. Automatic calibration of detector positions was implemented using an optical diode beam that defined the starting position of each motor, and by means of feedback algorithms controlling individual channels. As a result, the accuracy of zero position of 0.1 mm for all channels was achieved. We have also employed scanning procedures where detectors automatically covered the appropriate range around source positions. Thus, total scan time for a typical optical properties (OP) measurement throughout the phantom was about 1.5 minutes with point sources. The OP were determined based on the measured light fluence rates. These enhancements allow a tremendous improvement of treatment quality for a bulk tumor compared to the systems employed in previous clinical trials.

  10. 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.

  11. Photodynamic Therapy for Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    Chenjin Jin; Jian Ge; Shaobo Zhou; Huiyi Chen; Xiaojing Zhong; Ruzhang Jiang; Lingyan Chen; Lirong Chen

    2004-01-01

    Purpose: To evaluate short-term effects of single photodynamic therapy (PDT) for agerelated macular degeneration (AMD) accompanied with choroidal neovascularization (CNV).Methods: We analyzed retrospectively the effects of single PDT for 20 patients (20 eyes)with CNV caused by AMD. Corrected visual acuity, fluorescein angiography (FA) and optic coherence tomography (OCT) were examined before and after PDT. All patients were followed up at least 3 months.Results: At the end of 3-month follow-up, 5 eyes had vision progress, 15 eyes had vision stable and no eye had vision deterioration. Fluorescein angiography one week post PDT showed cessation of fluorescein leakage in 8 eyes with predominant classic CNV, and reduction of fluorescein leakage in 12 eyes with minimal classic CNV or occult CNV without classic component. At the 3-month following PDT fluorescein angiography showed fluorescein leakage reappeared in 4 of 8 eyes with predominant classic CNV.Among 12 eyes with minimal classic CNV or occult CNV without classic component, 9eyes showed decreased or unchanged fluorescein leakage, 3 eyes had a progression of fluorescein leakage. Optic coherence tomography showed obvious recovery of serous sensory retinal detachment after PDT.Conclusion: PDT may occlude or inhibit CNV caused by AMD in short term. No obvious side effects were noticed.

  12. 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.

  13. An update on photodynamic therapies in the treatment of onychomycosis.

    Science.gov (United States)

    Simmons, B J; Griffith, R D; Falto-Aizpurua, L A; Nouri, K

    2015-07-01

    Onychomycosis is a common fungal infection of the nails that is increasing in prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a therapeutic challenge that can lead to significant reductions in quality of life leading to both physical and psychological consequences. Current treatment modalities are difficult to implement due to the poor penetration of topical treatments to the nail bed, the slow growing nature of nails and the need for prolonged use of topical and/or oral medications. Standard of care medications have cure rates of 63-76% that leads to a high propensity of treatment failures and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and aminolevulinic acid (ALA) have been used as photosensitizers with approximately 630 nm light. These modalities are combined with pre-treatment of urea and/or microabrasion for better penetration. PDT treatments are well tolerated with only mild transient pain, burning and erythema. In addition, significant cure rates for patients who have contraindications to oral medications or failed standard medications can be obtained. With further enhancements in photosensitizer permeability, decreased pre-treatment and photosensitizer incubation times, PDT can be a more efficient and cost-effective in office based treatment for onychomycosis. However, more large-scale randomized control clinical trials are needed to access the efficacy of PDT treatments.

  14. Zinc phthalocyanine-conjugated with bovine serum albumin mediated photodynamic therapy of human larynx carcinoma

    Science.gov (United States)

    Silva, E. P. O.; Santos, E. D.; Gonçalves, C. S.; Cardoso, M. A. G.; Soares, C. P.; Beltrame, M., Jr.

    2016-10-01

    Phthalocyanines, which are classified as second-generation photosensitizers, have advantageous photophysical properties, and extensive studies have demonstrated their potential applications in photodynamic therapy. The present work describes the preparation of a new zinc phthalocyanine conjugated to bovine serum albumin (compound 4a) and its photodynamic efficiency in human larynx-carcinoma cells (HEp-2 cells). The unconjugated precursor (compound 4) was also studied. Compounds 4 and 4a penetrated efficiently into the cell, exhibiting cytoplasmic localization, and showed no cytotoxicity in the dark. However, high photodynamic activities were observed in HEp-2 cells after treatments with 5 µM photosensitizers and 4.5 J cm-2 light. These conditions were sufficient to decrease the cell viability to 57.93% and 32.75% for compounds 4 and 4a, respectively. The present results demonstrated high photodynamic efficiency of zinc phthalocyanine conjugated with bovine serum albumin in destroying the larynx-carcinoma cells.

  15. Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

    Science.gov (United States)

    Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2016-03-01

    Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

  16. Epithelial-mesenchymal interaction during photodynamic therapy-induced photorejuvenation.

    Science.gov (United States)

    Kim, Sue Kyung; Koo, Gi-Bang; Kim, You-Sun; Kim, You Chan

    2016-09-01

    Recently, several clinical studies reported that the photodynamic therapy (PDT) has photorejuvenation effects on the aged skin. Previously, our group introduced evidence of direct effect of PDT on cultured fibroblast (FB). PDT directly stimulated FBs and induced collagen synthesis through activation of extracellular signal-regulated kinase. In this study, we investigated indirect effect of PDT on the human dermal FB during photorejuvenation focused on the epithelial-mesenchymal interaction between keratinocyte (KC) and FB. The "low-level PDT" condition was used for PDT therapy to the cultured KC. Various kinds of cytokines in the supernatants of KC were evaluated by enzyme-linked immunosorbent assay. FBs were stimulated with the KC-conditioned medium (KCM) taken after PDT. The mRNA level of matrix metalloproteinases (MMPs), transforming growth factor (TGF)-β and collagen type Iα in the FB, was determined by real-time polymerase chain reaction. Clinical phtorejuvenation effect was also evaluated from nine patients who had PDT to treat actinic keratoses. Among the FB-stimulating cytokines, a significant elevation of interleukin (IL)-1α, IL-6, and tumor necrosis factor-α level in KCM was noted after PDT compared with controls. After stimulating FB with KCM, the mRNA of MMP-1 was decreased and the mRNA of collagen type Iα was increased compare to control. Clinically, fine wrinkles significantly reduced after PDT. However, coarse wrinkles were not recovered significantly. In conclusion, increased collagen synthesis may be mediated not only by direct effect of PDT on FB but also by indirect effect of PDT on FB through cytokines from KC, such as IL-1α, IL-6, and tumor necrosis factor-α.

  17. Epithelial-mesenchymal interaction during photodynamic therapy-induced photorejuvenation.

    Science.gov (United States)

    Kim, Sue Kyung; Koo, Gi-Bang; Kim, You-Sun; Kim, You Chan

    2016-09-01

    Recently, several clinical studies reported that the photodynamic therapy (PDT) has photorejuvenation effects on the aged skin. Previously, our group introduced evidence of direct effect of PDT on cultured fibroblast (FB). PDT directly stimulated FBs and induced collagen synthesis through activation of extracellular signal-regulated kinase. In this study, we investigated indirect effect of PDT on the human dermal FB during photorejuvenation focused on the epithelial-mesenchymal interaction between keratinocyte (KC) and FB. The "low-level PDT" condition was used for PDT therapy to the cultured KC. Various kinds of cytokines in the supernatants of KC were evaluated by enzyme-linked immunosorbent assay. FBs were stimulated with the KC-conditioned medium (KCM) taken after PDT. The mRNA level of matrix metalloproteinases (MMPs), transforming growth factor (TGF)-β and collagen type Iα in the FB, was determined by real-time polymerase chain reaction. Clinical phtorejuvenation effect was also evaluated from nine patients who had PDT to treat actinic keratoses. Among the FB-stimulating cytokines, a significant elevation of interleukin (IL)-1α, IL-6, and tumor necrosis factor-α level in KCM was noted after PDT compared with controls. After stimulating FB with KCM, the mRNA of MMP-1 was decreased and the mRNA of collagen type Iα was increased compare to control. Clinically, fine wrinkles significantly reduced after PDT. However, coarse wrinkles were not recovered significantly. In conclusion, increased collagen synthesis may be mediated not only by direct effect of PDT on FB but also by indirect effect of PDT on FB through cytokines from KC, such as IL-1α, IL-6, and tumor necrosis factor-α. PMID:27383261

  18. Photodynamic antimicrobial therapy in the treatment of denture stomatitis

    International Nuclear Information System (INIS)

    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 log10. 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)

  19. 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.

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

    Science.gov (United States)

    Libotte, Fabrizio; Sabatini, Silvia; Grassi, Felice Roberto

    2016-01-01

    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. PMID:27429618

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

    International Nuclear Information System (INIS)

    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 (HBLa+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

  2. 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 physiol......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...

  3. Analysis of superficial fluorescence patterns in nonmelanoma skin cancer during photodynamic therapy by a dosimetric model

    Science.gov (United States)

    Salas-García, I.; Fanjul-Vélez, F.; Arce-Diego, J. L.

    2016-03-01

    In this work the superficial fluorescence patterns in different nonmelanoma skin cancers and their photodynamic treatment response are analysed by a fluorescence based dosimetric model. Results show differences of even more than 50% in the fluorescence patterns as photodynamic therapy progresses depending on the malignant tissue type. They demonstrate the great relevance of the biological media as an additional dosimetric factor and contribute to the development of a future customized therapy with the assistance of dosimetric tools to interpret the fluorescence images obtained during the treatment monitoring and the differential photodiagnosis.

  4. Investigation of photodynamic therapy on streptococcus mutans of oral biofilm

    Institute of Scientific and Technical Information of China (English)

    Zhaohui Zou; Ping Gao; Huijuan Yin; Yingxin Li

    2008-01-01

    We investigated the effect of photodynamic therapy (PDT) with hematoporphyrin monomethyl ether (HMME) on the viability of Streptococcus mutans (S. mutans) cells on biofilms in vitro. Streptococcus mutans is the primary etiological agent of human dental caries. Since dental caries are localized infections, such plaque-related diseases would be well suited to PDT. The diode laser used in this study had the wavelength of 635 nm, whose output power was 10 mW and the energy density was 12.74 J/cm2. HMME was used as photosensitizer. Samples were prepared and divided into five groups: (1) HMME; (2) Laser; (3) HMME+Laser; (4) Control group (+) with chlorhexidine; and (5) Control group (-) with sterile physiological saline. Inoculum of S. mutans incubated with HMME also examined with fluorescence microscopy. PDT exhibited a significantly (P < 0.05) increased antimicrobial potential compared with 20 μm/mL HMME only, laser only, 0.05% chlorhexidine, and 0.9% sterile physiological saline, which reduced the S. mutans of the biofilm most effectively. Laser and 0.05% chlorhexidine were caused reduction in the viable counts of S. mutans significantly different (P < 0.05) also, but these two test treatments did not statistically differ from each other. HMME group did not statistically differ with negative control group. Fluorescence microscopy indicated that HMME localized primarily in the S. mutans of the biofilm. It was demonstrated that HMME-mediated PDT was efficient at killing S. mutans of biofilms and a useful approach in the treatment of dental plaque-related diseases.

  5. Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy

    Science.gov (United States)

    Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang

    2005-01-01

    Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

  6. Modulation of inflammatory response of wounds by antimicrobial photodynamic therapy

    Science.gov (United States)

    Sharma, Mrinalini; Gupta, Pradeep Kumar

    2015-01-01

    Background and aims: Management of infections caused by Pseudomonas aeruginosa is becoming difficult due to the rapid emergence of multi-antibiotic resistant strains. Antimicrobial photodynamic therapy (APDT) has a lot of potential as an alternative approach for inactivation of antibiotic resistant bacteria. In this study we report results of our investigations on the effect of poly-L-lysine conjugate of chlorine p6 (pl-cp6) mediated APDT on the healing of P.aeruginosa infected wounds and the role of Nuclear Factor kappa B (NF-kB) induced inflammatory response in this process. Materials and method: Excisional wounds created in Swiss albino mice were infected with ∼107 colony forming units of P.aeruginosa. Mice with wounds were divided into three groups: 1) Uninfected, 2) Infected, untreated control (no light, no pl-cp6), 3) Infected, APDT. After 24 h of infection (day 1 post wounding), the wounds were subjected to APDT [pl-cp6 applied topically and exposed to red light (660 ± 25 nm) fluence of ∼ 60 J/cm2]. Subsequent to APDT, on day 2 and 5 post wounding (p.w), measurements were made on biochemical parameters of inflammation [toll like receptor-4 (TLR-4), NF-kB, Inteleukin (IL)-[1α, IL-β, and IL-2)] and cell proliferation [(fibroblast growth factor-2 (FGF-2), alkaline phosphatase (ALP)]. Results: In comparison with untreated control, while expression of TLR-4, NF-kB (p105 and p50), and proinflammatory interleukins (IL-1α, IL-1β,IL-2) were reduced in the infected wounds subjected to APDT, the levels of FGF-2 and ALP increased, on day 5 p.w. Conclusion: The measurements made on the inflammatory markers and cell proliferation markers suggest that APDT reduces inflammation caused by P.aeruginosa and promotes cell proliferation in wounds. PMID:26557735

  7. Photodynamic therapy and diagnosis of lower lip cancer with photosense

    Directory of Open Access Journals (Sweden)

    S. V. Evstigneev

    2014-01-01

    Full Text Available Results of diagnosis and treatment in 32 patients with lower lip cancer using photodynamic therapy (PDT with photosensitizer Photosense are represented. 15 patients had stage I of disease, in 12 – stage II and in 5 – stage III. Photosensitizer Photosense was administered at dose of 0.5 mg/kg body weight in 20 patients and at dose of 0.8 mg/kg – in 12 patients as single intravenous infusion. During the treatment the fluorescent diagnosis (FD was performed. The average power of diagnostic laser irradiation was 2 mW, light dose on tissue surface was < 1 J/cm2. Power density of therapeutic laser irradiation accounted for 150–300 mW/cm2, light dose of one session was 200-300 J/cm2. First session of PDT was performed 24 h after drug injection, the interval between following sessions accounted for 24 h. The number of session varied from 3 to 5. The results of FD showed the increase of fluorescent intensity in the center of tumor from 14.9 up to 150.8 r.u. 24 h after drug injection, this parameter in the normal mucosa increased from 13,4 to 88,3 r.u. The side-effects of PDT with Photosense included pain syndrome, which was managed by non-opioid analgesics in all 10 patients. The signs of phototoxycity were observed in 9 patients. Two months after PDT 22 (68.7% patients had complete regression of tumor lesion, the response in 8 (25% patients was defined as partial, 2 (6.3% patients had stabilization of tumor growth. 

  8. New design of textile light diffusers for photodynamic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cochrane, Cédric, E-mail: cedric.cochrane@ensait.fr [Univ Lille Nord de France, F-59000 Lille (France); ENSAIT, GEMTEX, F-59100 Roubaix (France); Mordon, Serge R.; Lesage, Jean Claude [Univ Lille Nord de France, F-59000 Lille (France); INSERM U 703, Lille University Hospital — CHRU (France); Koncar, Vladan [Univ Lille Nord de France, F-59000 Lille (France); ENSAIT, GEMTEX, F-59100 Roubaix (France)

    2013-04-01

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

  9. Canine treatment with SnET2 for photodynamic therapy

    Science.gov (United States)

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

    1990-07-01

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

  10. New design of textile light diffusers for photodynamic therapy

    International Nuclear Information System (INIS)

    A homogeneous and reproducible fluence delivery rate during clinical photodynamic therapy (PDT) plays a determinant role in preventing under- or overtreatment. PDT applied in dermatology has been carried out with a wide variety of light sources delivering a broad range of more or less adapted light doses. Due to the complexities of the human anatomy, these light sources do not in fact deliver a uniform light distribution to the skin. Therefore, the development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of plastic optical fiber (POF) into textile structures could offer an interesting alternative. In this article, a textile light diffuser (TLD) has been developed using POF and Polyester yarns. Predetermined POF macrobending leads to side emission of light when the critical angle is exceeded. Therefore, a specific pattern based on different satin weaves has been developed in order to improve light emission homogeneity and to correct the decrease of side emitted radiation intensity along POF. The prototyped fabrics (approximately 100 cm2: 5 × 20 cm) were woven using a hand loom, then both ends of the POF were coupled to a laser diode (5 W, 635 nm). The fluence rate (mW/cm2) and the homogeneity of light delivery by the TLD were evaluated. Temperature evolution, as a function of time, was controlled with an infrared thermographic camera. When using a power source of 5 W, the fluence rate of the TLD was 18 ± 2.5 mw/cm2. Due to the high efficiency of the TLD, the optical losses were very low. The TLD temperature elevation was 0.6 °C after 10 min of illumination. Our TLD meets the basic requirements for PDT: homogeneous light distribution and flexibility. It also proves that large (500 cm2) textile light diffusers adapted to skin, but also to peritoneal or pleural cavity, PDTs can be easily produced by textile manufacturing processes

  11. Tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine for photodynamic cancer therapy.

    Science.gov (United States)

    Kuzyniak, Weronika; Ermilov, Eugeny A; Atilla, Devrim; Gürek, Ayşe Gül; Nitzsche, Bianca; Derkow, Katja; Hoffmann, Björn; Steinemann, Gustav; Ahsen, Vefa; Höpfner, Michael

    2016-03-01

    Photodynamic therapy (PDT) has emerged as an effective and minimally invasive treatment option for several diseases, including some forms of cancer. However, several drawbacks of the approved photosensitizers (PS), such as insufficient light absorption at therapeutically relevant wavelengths hampered the clinical effectiveness of PDT. Phthalocyanines (Pc) are interesting PS-candidates with a strong light absorption in the favourable red spectral region and a high quantum yield of cancer cell destroying singlet oxygen generation. Here, we evaluated the suitability of tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as novel PS for PDT. ZnPc-induced phototoxicity, induction of apoptosis as well as cell cycle arresting effects was studied in the human gastrointestinal cancer cell lines of different origin. Photoactivation of ZnPc-pretreated (1-10 μM) cancer cells was achieved by illumination with a broad band white light source (400-700 nm) at a power density of 10 J/cm(2). Photoactivation of ZnPc-loaded cells revealed strong phototoxic effects, leading to a dose-dependent decrease of cancer cell proliferation of up to almost 100%, the induction of apoptosis and a G1-phase arrest of the cell cycle, which was associated with decrease in cyclin D1 expression. By contrast, ZnPc-treatment without illumination did not induce any cytotoxicity, apoptosis, cell cycle arrest or decreased cell growth. Antiangiogenic effects of ZnPc-PDT were investigated in vivo by performing CAM assays, which revealed a marked degradation of blood vessels and the capillary plexus of the chorioallantoic membrane of fertilized chicken eggs. Based on our data we think that ZnPc may be a promising novel photosensitizer for innovative PDT. PMID:26162500

  12. Interstitial photodynamic therapy for the prostate: a canine feasibility study

    Science.gov (United States)

    Shetty, Sugandh D.; Sirls, Larry T.; Chen, Qun; Hetzel, Fred W.; Cerny, Joseph C.

    1996-05-01

    Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.

  13. New design of textile light diffusers for photodynamic therapy.

    Science.gov (United States)

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

    2013-04-01

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

  14. 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.

  15. The design of a robotic multichannel platform for photodynamic therapy

    Science.gov (United States)

    Hu, Yida; Finlay, Jarod C.; Zhu, Timothy C.

    2009-06-01

    A compact robotic platform is designed for simultaneous multichannel motion control for light delivery and dosimetry during interstitial photodynamic therapy (PDT). Movements of light sources and isotropic detectors are controlled by individual motors along different catheters for interstitial PDT. The robotic multichannel platform adds feedback control of positioning for up to 16 channels compared to the existing dual-motor system, which did not have positioning encoders. A 16-channel servo motion controller and micro DC motors, each with high resolution optical encoder, are adopted to control the motions of up to 16 channels independently. Each channel has a resolution of 0.1mm and a speed of 5cm/s. The robotic platform can perform light delivery and dosimetry independently, allowing arbitrary positioning of light sources and detectors in each catheter. Up to 16 compact translational channels can be combined according to different operational scheme with real-time optimal motion planning. The characteristic of high speed and coordinating motion will make it possible to use short linear sources (e.g., 1- cm) to deliver uniform PDT treatment to a bulk tumor within reasonable time by source stepping optimization of multiple sources simultaneously. Advanced robotic control algorithm handles the various unexpected circumstance in clinical procedure, e.g., positiontorque/ current control will be applied to prevent excessive force in the case of resistance in the fiber or motorized mechanism. The robotic platform is fully compatible with operation room (OR) environment and improves the light delivery and dosimetry in PDT. It can be adopted for diffusing optical tomography (DOT), spectroscopic DOT and fluorescent spectroscopy.

  16. Nanophotonic ensembles for targeted multi-photon photodynamic therapy

    Science.gov (United States)

    Spangler, Charles W.; Meng, Fanqing; Gong, Aijun; Drobizhev, Mikhail A.; Karotki, Aliaksandr; Rebane, Aleksander, II

    2004-06-01

    There has been a dramatic increase in the application of new technologies for the treatment of cancerous tumors over the past decade, but for the most part, the treatment of most tumors still involves some combination of invasive surgery, chemotherapy and radiation treatments. Photodynamic therapy (PDT), which involves the activation of an administered compound with laser light followed by a series of events leading to programmed cell death of the tumor, has been proposed as a noninvasive alternative treatment to replace the standard surgery/chemotherapy/radiation protocol. However, currently approved PDT agents operate in the Visible portion of the spectrum, and laser light in this region cannot penetrate the skin more than a few millimeters. Two-photon irradiation using more highly penetrating Near-infrared (NIR) light in the tissue transparency window (700-1000 nm) has been proposed for the treatment of subcutaneous tumors, but most porphyrins exhibit extremely small two-photon cross-sections. Classical PDT also suffers from the lengthy time necessary for accumulation at the tumor site, a relative lack of discrimination between healthy and diseased tissue, particularly at the tumor margins, and difficulty in clearing from the system in a reasonable amount of time. We have recently discovered a new design paradigm for porphyrins with greatly enhanced two-photon cross-sections, and are now proposing a nano-ensemble that would also incorporate small molecule targeting agents, and possibly one-photon NIR imaging agents along with these porphyrins in one therapeutic agent. Thus these ensembles would incorporate targeting/imaging/PDT functions in one therapeutic agent, and hold the promise of single-session outpatient treatment of a large variety of subcutaneous tumors.

  17. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    Science.gov (United States)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  18. Fluorescence diagnosis and photodynamic therapy of skin cancer with alasens

    Directory of Open Access Journals (Sweden)

    S. V. Evstifeev

    2014-01-01

    Full Text Available The results of treatment in patients with skin cancer using the method of photodynamic therapy (PDT with alasens are represented in the article. The study enrolled 25 patients with stage 1 tumor including 23 patients with previously untreated tumors and 2 – with recurrent disease. Superficial tumor was diagnosed in 17 patients and 8 patients had nodal tumor. Alasens was used locally as application of 20% ointment on involved skin area with 6h exposure. The PDT session was performed on a single occasion immediately after the end of exposure (power density of laser irradiation of 50–100 mW/cm2, light dose – 150–200 J/cm2. All patients had fluorescence diagnosis (FD prior to application of the ointment and before PDT. The results of FD showed that intensity of porphyrin fluorescence in tumor prior to administration of alasens had near no difference from intensity of porphyrin fluorescence in normal skin (12.5±0.7 and 10.0±0.7 r.u., respectively. Six hours after application of the ointment with alasens the fluorescence intensity of protoporphyrin IX increased almost 5-fold (59.7±5.3 r.u., the fluorescence intensity in normal skin remained near baseline level during the follow-up period (maximally 11.6±1.0 r.u.. Two months after PDT the complete tumor regression was confirmed in 21 patients, partial – in 3 and stabilization of tumor growth in 1 patient. In addition, patients with superficial disease had complete regression in 94.1% of cases and partial regression in 5.9% while for patients with nodal tumor – 62.5% and 25%, respectively, stabilization – in 12.5%. 

  19. Fluorescent MoS2 Quantum Dots: Ultrasonic Preparation, Up-Conversion and Down-Conversion Bioimaging, and Photodynamic Therapy.

    Science.gov (United States)

    Dong, Haifeng; Tang, Songsong; Hao, Yansong; Yu, Haizhu; Dai, Wenhao; Zhao, Guifeng; Cao, Yu; Lu, Huiting; Zhang, Xueji; Ju, Huangxian

    2016-02-10

    Small size molybdenum disulfide (MoS2) quantum dots (QDs) with desired optical properties were controllably synthesized by using tetrabutylammonium-assisted ultrasonication of multilayered MoS2 powder via OH-mediated chain-like Mo-S bond cleavage mode. The tunable up-bottom approach of precise fabrication of MoS2 QDs finally enables detailed experimental investigations of their optical properties. The synthesized MoS2 QDs present good down-conversion photoluminescence behaviors and exhibit remarkable up-conversion photoluminescence for bioimaging. The mechanism of the emerging photoluminescence was investigated. Furthermore, superior (1)O2 production ability of MoS2 QDs to commercial photosensitizer PpIX was demonstrated, which has great potential application for photodynamic therapy. These early affording results of tunable synthesis of MoS2 QDs with desired photo properties can lead to application in fields of biomedical and optoelectronics.

  20. Fluorescent MoS2 Quantum Dots: Ultrasonic Preparation, Up-Conversion and Down-Conversion Bioimaging, and Photodynamic Therapy.

    Science.gov (United States)

    Dong, Haifeng; Tang, Songsong; Hao, Yansong; Yu, Haizhu; Dai, Wenhao; Zhao, Guifeng; Cao, Yu; Lu, Huiting; Zhang, Xueji; Ju, Huangxian

    2016-02-10

    Small size molybdenum disulfide (MoS2) quantum dots (QDs) with desired optical properties were controllably synthesized by using tetrabutylammonium-assisted ultrasonication of multilayered MoS2 powder via OH-mediated chain-like Mo-S bond cleavage mode. The tunable up-bottom approach of precise fabrication of MoS2 QDs finally enables detailed experimental investigations of their optical properties. The synthesized MoS2 QDs present good down-conversion photoluminescence behaviors and exhibit remarkable up-conversion photoluminescence for bioimaging. The mechanism of the emerging photoluminescence was investigated. Furthermore, superior (1)O2 production ability of MoS2 QDs to commercial photosensitizer PpIX was demonstrated, which has great potential application for photodynamic therapy. These early affording results of tunable synthesis of MoS2 QDs with desired photo properties can lead to application in fields of biomedical and optoelectronics. PMID:26761391

  1. Own Experience in Treatment of Patients with Penile Cancer Using Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Elena Filonenko

    2015-01-01

    radachlorine. All patients had no complications. Complete regression was achieved in 9 patients, and partial regression in 2. Thus, the results showed that photodynamic therapy for penile cancer stage Tis-1N0M0 permits performing organ-preserving treatment with satisfactory oncological results and no impairment of patient’s quality of life.

  2. Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts

    DEFF Research Database (Denmark)

    Stender, I M; Na, R; Fogh, H;

    2000-01-01

    Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) followed by irradiation with incoherent light (ALA-PDT) for recalcitrant warts have had beneficial results. Therefore, we undertook a randomised, parallel, double-blind clinical trial of ALA-PDT versus placeboPDT for recalcitrant...

  3. Allergic contact dermatitis to methyl aminolevulinate after photodynamic therapy in 9 patients

    DEFF Research Database (Denmark)

    Hohwy, Thomas; Andersen, Klaus Ejner; Sølvsten, Henrik;

    2007-01-01

    This report describes 9 patients who developed allergic contact dermatitis to methyl aminolevulinate used for photodynamic therapy (PDT). The risk of developing contact allergy to methyl aminolevulinate in PDT treated patients was calculated to 1% after an average of 7 treatments (range 2...

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

    NARCIS (Netherlands)

    B. karakullukcu (Baris); K. Oudenaarde (Kim); M.P. Copper (Marcel); W.M.C. Klop; R. van Veen (Robert); M. Wildeman (Maarten); I. Bing Tan

    2010-01-01

    textabstractThe 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

  5. Photodynamic therapy for palpebral and conjunctival proliferative vascular tumors: clinical case report.

    Science.gov (United States)

    Sanchez, Carlos Gustavo; Caballero Chávez, Yolanda V; Plazola, Sara

    2009-01-01

    Photodynamic therapy (PDT) has been widely used in ophthalmology for the treatment of diverse pathologies, but no experience has been reported in the handling of patients with palpebral vascular and conjunctive malformations with PDT, we describe the case of one patient with a palpebral proliferative vascular tumor, treated successfully using the PDT as a new treatment alternative.

  6. 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 is a

  7. Photodynamic therapy of oral cancer - A review of basic mechanisms and clinical applications

    NARCIS (Netherlands)

    Nauta, JM; vanLeengoed, HLLM; Roodenburg, JLN; Witjes, MJH; Vermey, A

    1996-01-01

    Photodynamic therapy (PDT) is an experimental cancer treatment modality. PDT is based on the accumulation of a photosensitive dye in premalignant and malignant lesions. A certain period of time after the dye has been administered, tumor tissue may contain more of the sensitizer then the surrounding

  8. 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 pote

  9. Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Rui Chen

    2011-01-01

    Full Text Available Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs, which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource.

  10. Multifunctional gold nanoparticles for photodynamic therapy of cancer

    Science.gov (United States)

    Khaing Oo, Maung Kyaw

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

  11. Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)

    OpenAIRE

    Miya Ishihara; Shinpei Okawa; Toshihiro Kushibiki; Takeshi Hirasawa

    2013-01-01

    Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will a...

  12. Photodynamic Therapy as Novel Treatment for Halitosis in Adolescents: A Case Series Study

    Science.gov (United States)

    Lopes, Rubia Garcia; de Santi, Maria Eugenia Simões Onofre; Franco, Bruno Edin; Deana, Alessandro Melo; Prates, Renato Araujo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Ferrari, Raquel Agnelli Mesquita; Bussadori, Sandra Kalil

    2014-01-01

    Introduction: Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% of cases and systemic in 10% of cases. The foul odor is caused mainly by 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 with and without the combination of chemical agents has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by the photosensitizing dye. The aim of the present case series study was to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using a sulfide meter (Halimeter®). Methods: Five adolescents aged 14 to 16 years were evaluated using a sulfide meter before and one hour after photodynamic therapy, which involved the use of methylene blue 0.005% on the middle third and posterior thirds of the dorsum of the tongue and nine points of laser irradiation in the red band (660 nm) with an energy dose of 9 J, power output of 100 mW and 90-seconds exposure time. Results: A 31.8% reduction in the concentration of volatile sulfur compounds was found in the comparison of the initial and final readings. The statistically significant reduction (p = 0.0091) led to an absence of halitosis following treatment (mean: 58.2 ppb). Conclusion: Photodynamic therapy seems to be effective on reduction the concentration of volatile sulfur compounds.Considering the positive effects of photodynamic therapy in this case series, further studies involving microbiological analyses should be conducted to allow comparisons of the results. PMID:25653814

  13. Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy.

    Science.gov (United States)

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-07-01

    Correction for 'Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a. PMID:27300478

  14. Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy

    Science.gov (United States)

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-06-01

    Correction for `Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a.

  15. Combination of photodynamic therapy with intravitreal bevacizumab for post-peribulbar anesthesia (penetrating trauma)-persistent choroidal neovascular membrane

    OpenAIRE

    Shah Nikunj; Shah Urmi

    2008-01-01

    We report a case of a choroidal neovascular membrane (CNVM) following ocular penetration during peribulbar anesthesia in a 55- year-old male patient. A combination of photodynamic therapy with intravitreal bevacizumab led to resolution of the persistent CNVM.

  16. Application of benzo[a]phenoxazinium chlorides in Antimicrobial Photodynamic Therapy of Candida albicans biofilms.

    Science.gov (United States)

    Lopes, Marisa; Alves, Carlos Tiago; Rama Raju, B; Gonçalves, M Sameiro T; Coutinho, Paulo J G; Henriques, Mariana; Belo, Isabel

    2014-12-01

    The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100-300 μM for 3 or 18 h followed by illumination at 12 or 36 J cm(-2), using a xenon arc lamp (600 ± 2 nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300 μM of FSc with 18 h of incubation, followed by illumination at 36 J cm(-2). Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections.

  17. In vitro evaluation of photodynamic therapy using curcumin on Leishmania major and Leishmania braziliensis.

    Science.gov (United States)

    Pinto, Juliana Guerra; Fontana, Letícia Correa; de Oliveira, Marco Antonio; Kurachi, Cristina; Raniero, Leandro José; Ferreira-Strixino, Juliana

    2016-07-01

    Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 μg/ml up to 7.8 μg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm(2) at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed. PMID:27056699

  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. 5-Aminolevulinic Acid Photodynamic Therapy combined with CO2 laser therapy in treatment of laryngeal papilloma: Case report.

    Science.gov (United States)

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao; Huang, Zheng

    2016-06-01

    This article describes the case of 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy in the treatment of three patients with juvenile laryngeal papilloma. Laryngeal papilloma Clinically, it features rapid growth, multi-focus, frequent recurrence and possibility of spreading to the lower respiratory tract. ALA-PDT via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy is safe and effective for clearing laryngeal papilloma, laryngeal papilloma was fully removed from the three patients, with no recurrence during the 6-24 months of follow-up medical examination. 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser can be used for treating laryngeal papilloma. PMID:27045601

  20. 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.

  1. Spectral matching technology for light-emitting diode-based jaundice photodynamic therapy device

    Science.gov (United States)

    Gan, Ru-ting; Guo, Zhen-ning; Lin, Jie-ben

    2015-02-01

    The objective of this paper is to obtain the spectrum of light-emitting diode (LED)-based jaundice photodynamic therapy device (JPTD), the bilirubin absorption spectrum in vivo was regarded as target spectrum. According to the spectral constructing theory, a simple genetic algorithm as the spectral matching algorithm was first proposed in this study. The optimal combination ratios of LEDs were obtained, and the required LEDs number was then calculated. Meanwhile, the algorithm was compared with the existing spectral matching algorithms. The results show that this algorithm runs faster with higher efficiency, the switching time consumed is 2.06 s, and the fitting spectrum is very similar to the target spectrum with 98.15% matching degree. Thus, blue LED-based JPTD can replace traditional blue fluorescent tube, the spectral matching technology that has been put forward can be applied to the light source spectral matching for jaundice photodynamic therapy and other medical phototherapy.

  2. Efficacy of topical photodynamic therapy for keratoacanthomas: A case-series of four patients

    Directory of Open Access Journals (Sweden)

    Maria M Farias

    2012-01-01

    Full Text Available Topical photodynamic therapy (PDT is an excellent treatment option for various non-melanoma skin cancers and precancerous lesions, including actinic keratosis, Bowen′s disease, and basal cell carcinoma. The clinical use of PDT includes a broad range of neoplastic, inflammatory, and infectious skin diseases. There is also anecdotal evidence suggesting the efficacy of PDT for the treatment of keratoacanthomas (KA. We report a case-series of four patients with solitary KA confirmed by histology, treated with topical PDT with methylaminolevulinic acid (MAL cream. After three sessions of PDT, the lesions completely disappeared. There was no evidence of recurrence and excellent cosmetic outcome was achieved after three years of follow-up. Topical photodynamic therapy with MAL can be a therapeutic alternative for KA with good clinical and cosmetic outcomes.

  3. Soft versus hard nanoparticles in the delivery of aromatic macrocycles for photodynamic therapy of cancer

    Directory of Open Access Journals (Sweden)

    Alejandro Díaz-Moscoso

    2012-01-01

    Full Text Available Background: Photodynamic therapy is a medical strategy to treat some types of cancer. It is based on the use of a photosensitiser, usually porphyrin or phthalocyanine derivatives, to generate toxic species in the cells upon light irradiation. Aim: An overview of the different types of nanoparticles already investigated to deliver the photosensitisers until its target is given in this review. Materials and Methods: Previous literature and various scientific search engines were used for the review. Results: A classification of the nanoparticles based on the nature of their components, ‘hard’-inorganic and ‘soft’-organic, is made and several advantages and disadvantages about their uses are pointed out. Also, a comparative summary is outlined. Conclusion: There are still some drawbacks that need to be sorted out for photodynamic therapy to become a generalised cancer treatment. These could be overcome by using nanoparticles as carriers for the photosensitisers.

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

    Directory of Open Access Journals (Sweden)

    Marica B Ericson

    2008-03-01

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

  5. Clinical effect of photodynamic therapy on primary carious dentin after partial caries removal.

    Science.gov (United States)

    Neves, Pierre Adriano Moreno; Lima, Leonardo Abrantes; Rodrigues, Fernanda Cristina Nogueira; Leitão, Tarcisio Jorge; Ribeiro, Cecília Cláudia Costa

    2016-05-20

    This study was conducted to assess the clinical effect of photodynamic therapy (PDT) in the decontamination of the deep dentin of deciduous molars submitted to partial removal of carious tissue. After cavity preparation, dentin samples were taken from the pulp wall of nineteen deciduous molars before and after PDT application. Remaining dentin was treated with 0.01% methylene blue dye followed by irradiation with an InGaAlP diode laser (λ - 660 nm; 40 mW; 120 J/cm2; 120 s). Dentin samples were microbiologically assessed for the enumeration of total microorganisms, Lactobacillus spp. and mutans streptococci. There was no significant difference in the number of colony-forming units (CFU) for any of the microorganisms assessed (p > 0.05). Photodynamic therapy, using 0.01% methylene blue dye at a dosimetry of 120 J/cm2 would not be a viable clinical alternative to reduce bacterial contamination in deep dentin. PMID:27223131

  6. Cold Water and Pauses in Illumination Reduces Pain During Photodynamic Therapy: A Randomized Clinical Study

    DEFF Research Database (Denmark)

    Wiegell, S.R.; Haedersdal, M.; Wulf, H.C.

    2009-01-01

    symmetrical areas and cooled with either cold-water-spray or cold-water-pack (Coo]Pack). Treatment areas were cooled during either the first or second period of illumination, which were separated by a 3-min pause in illumination. Pain intensity was scored from 0 to 10. Water-spray reduced the mean pain score...... by 1.2 points (p=0.030) and CoolPack by 1.3 points (p=0.007) during the first half of the illumination. Pain intensity decreased during the pause by 3.7 points in water-spray patients (pCoolPack patients (pcooling resulted in a minor reduction in pain......Pain is the main acute adverse event during photodynamic therapy of skin lesions. The objective of this randomized study was to evaluate the pain-relieving effect of pauses and cooling during illumination. Twenty-four patients with actinic keratoses were treated with photodynamic therapy in two...

  7. Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance.

    Science.gov (United States)

    Zhang, Wei; Shen, Jianliang; Su, Hua; Mu, Ge; Sun, Jing-Hua; Tan, Cai-Ping; Liang, Xing-Jie; Ji, Liang-Nian; Mao, Zong-Wan

    2016-06-01

    Combination therapy shows great promise in circumventing cisplatin resistance. We report herein the development of a novel nanoscale drug delivery system (nDDS) based nanotherapeutic that combines chemotherapy and photodynamic therapy (PDT) into one single platform to achieve synergistic anticancer capacity to conquer cisplatin resistance. Mesoporous silica nanoparticle (MSNs) was used as the drug delivery vector to conjugate cisplatin prodrug and to load photosensitizer chlorin e6 (Ce6) to afford the dual drug loaded delivery system MSNs/Ce6/Pt. The hybrid nanoparticles have an average diameter of about 100 nm and slightly positive surface charge of about 18.2 mV. The MSNs/Ce6/Pt nanoparticles can be efficiently internalized by cells through endocytosis, thereby achieving much higher cellular Pt uptake than cisplatin in cisplatin-resistant A549R lung cancer cells. After 660 nm light irradiation (10 mW/cm(2)), the cellular reactive oxygen species (ROS) level in MSNs/Ce6/Pt treated cells was elevated dramatically. As a result of these properties, MSNs/Ce6/Pt exhibited very potent anticancer activity against A549R cells, giving a half-maximal inhibitory concentration (IC50) value for the combination therapy of 0.53 μM, much lower than that of cisplatin (25.1 μM). This study suggests the great potential of nDDS-based nanotherapeutic for combined chemo-photodynamic therapy to circumvent cisplatin resistance.

  8. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy

    OpenAIRE

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

    2011-01-01

    Photodynamic therapy, mediated by exogenously administered aminolevulinic acid (ALA-PDT) followed by exposure to a laser or broadband light source, is a promising modality for treatment of many types of cancers, but it remains inadequate to treat large, deep solid tumors. Here we report that calcitriol, the active form of Vitamin D3, can be administered prior to ALA as a non-toxic preconditioning regimen to markedly increase the efficacy of ALA-PDT. Using mouse models of squamous skin cancer ...

  9. Photodynamic Therapy for Superficial Esophageal Cancer Using an Excimer Dye Laser

    OpenAIRE

    Seishiro Mimura; Toru Otani; Shigeru Okuda

    1994-01-01

    In order to improve the therapeutic effectiveness of photodynamic therapy with Photofrin II and laser light for superficial esophageal cancer, we employed an excimer dye laser instead of an argon dye laser. Eight superficial esophageal cancer lesions (7 cases) were treated. Of these 8 lesions, 6 were cured by initial treatment, while one lesion required another treatment. The final rate of cure was 88% (7/8).

  10. Photodynamic therapy for breast cancer in a BALB/c mouse model

    OpenAIRE

    Ahn, Tae-Gyu; Lee, Byoung-Rai; Choi, Eun-Young; Kim, Dong Won; Han, Sei-Jun

    2012-01-01

    Objective Photodynamic therapy (PDT) has been used for superficial neoplasms and its usage has been recently extended to deeper lesions. The purpose of this study was to observe whether or not PDT can cure breast cancer in the solid tumor model, and to define the critical point of laser amount for killing the cancer cells. Methods Twenty four BALB/c mouse models with subcutaneous EMT6 mammary carcinomas were prepared. Mice were divided into eight groups depending on the amount of illumination...

  11. Investigating the effect of photodynamic therapy on nerves using tissue engineered culture models

    OpenAIRE

    Wright, K.E.; Liniker, E; MacRobert, A J; Brown, R A; Saffrey, M. J.; Phillips, J B

    2006-01-01

    Introduction: Photodynamic therapy (PDT) shows potential as an effective treatment for prostate cancer. Clinical observations indicate that this approach causes fewer nerve damage related side-effects than conventional treatments. The aim here is to investigate the effect of PDT on nerve tissue using engineered 3-dimensional cell culture models. Initial experiments focussed on establishing photosensitiser localisation in neurones and Schwann cells, then developing a model for simulating ne...

  12. 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

    2014-12-01

    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.

  13. Urticaria after methyl aminolevulinate photodynamic therapy in a patient with nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Wolfe, Christopher M; Green, W Harris; Hatfield, H Keith; Cognetta, Armand B

    2012-11-01

    Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized in several countries for the treatment of basal cell carcinoma, but allergic sensitization has been reported by the manufacturer. To the best of our knowledge, we report the first case of urticaria following MAL-PDT in a patient with nevoid basal cell carcinoma syndrome. Prophylactic use of antihistamines may allow continued use of MAL-PDT in this setting.

  14. A 10-Year Retrospective Analysis of Methyl Aminolevulinate Photodynamic Therapy Consultation at the Hospital de Braga

    OpenAIRE

    Brito, C; Resende, C.; Oliveira, P.

    2016-01-01

    Introduction Photodynamic therapy (PDT) is a well-established treatment for actinic keratosis (AK), basal cell carcinoma (BCC), and Bowen’s disease (BD). The object of this study was to describe the results of a retrospective analysis of patients treated with methyl aminolevulinate PDT (MAL-PDT) with red light, over the past decade at the Hospital de Braga (Braga, Portugal). Methods This study is based on the retrospective analysis of the clinical records of patients treated with MAL-PDT from...

  15. Covalently Assembled Dipeptide Nanospheres as Intrinsic Photosensitizers for Efficient Photodynamic Therapy in Vitro.

    Science.gov (United States)

    Yang, Xiaoke; Fei, Jinbo; Li, Qi; Li, Junbai

    2016-05-01

    Monodispersed diphenylalanine-based nanospheres with excellent biocompatibility are fabricated through a facile covalent reaction-induced assembly. Interestingly, the nanospheres exhibit red autofluorescence. Most importantly, such assembled dipeptide nanospheres can serve as intrinsic photosensitizer to convert O2 to singlet oxygen ((1) O2 ). Thus, photodynamic therapy in vitro can be achieved effectively. The versatile strategy could be extended to other biomolecules containing a primary amine group for the fabrication of potential intrinsic photosensitizers. PMID:26934079

  16. Photodynamic Therapy: Occupational Hazards and Preventative Recommendations for Clinical Administration by Healthcare Providers

    OpenAIRE

    Breskey, John D.; Lacey, Steven E.; Vesper, Benjamin J.; Paradise, William A.; James A. Radosevich; Colvard, Michael D.

    2013-01-01

    Objective: Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these...

  17. Antimicrobial photodynamic therapy in the colon: delivering a light punch to the guts?

    OpenAIRE

    Wainwright, Mark; Dai, Tianhong; Michael R Hamblin

    2011-01-01

    A paper in this issue of Photochemistry and Photobiology by Cassidy et al describes the use of a sophisticated drug delivery vehicle prepared by the hot melt extrusion process to deliver photosensitizers to the colon. The smart vehicle protects its cargo through the acidic environment of the stomach but releases the active photosensitizers in the higher pH and anaerobic environment of the colon. The goal is to use photodynamic therapy (PDT) to destroy pathogenic microorganisms that can cause ...

  18. Spectroscopical study of bacteriopurpurinimide-naphthalimide conjugates for fluorescent diagnostics and photodynamic therapy

    OpenAIRE

    Panchenko, Pavel A.; Sergeeva, Antonina N.; Fedorova, Olga A.; Fedorov, Yuri V.; Reshetnikov, Roman I.; Schelkunova, Anastasiya E.; Grin, Michail A.; Mironov, Andrey F.; Jonusauskas, Gediminas

    2014-01-01

    International audience Two novel bis(chromophoric) dyads ABPI-NI1 and ABPI-NI2 containing 1,8-naphthalimide and bacteriopurpurinimide units linked by p-phenylene-methylene (ABPI-NI1) and pentamethylene (ABPI-NI2) spacers were prepared to test their ability to be used in the design of effective agents for both photodynamic therapy (PDT) and fluorescent tumor imaging. Photophysical studies revealed that the emission from the naphthalimide chromophore in both conjugates was partially quenched...

  19. Successful treatment of recalcitrant folliculitis barbae and pseudofolliculitis barbae with photodynamic therapy

    DEFF Research Database (Denmark)

    Diernaes, Jon Erik Fraes; Bygum, Anette

    2013-01-01

    Folliculitis and pseudofolliculitis barbae typically affects men with curly hair who shave too close. Treatment modalities vary in effectiveness and include improved hair removal methods, topical corticosteroids, topical and oral antibiotics, and retinoids as well as laser surgery. We report...... a novel treatment of recalcitrant pseudofolliculitis barbae and confirm effectiveness in recalcitrant folliculitis in a 58-year old man who responded completely following photodynamic therapy with methyl aminolevulinate....

  20. 膀胱癌的光动力学治疗%Photodynamic Therapy on Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    陈伟; 薄隽杰

    2008-01-01

    光动力学疗法(photodynamic therapy,PDT)是一种新兴的治疗肿瘤的方法,近来被应用于膀胱肿瘤的治疗.笔者就PDT治疗膀胱癌的原理、基本技术、适应证及并发症、疗效及发展前景等做一综述.

  1. Effectiveness of Photodynamic Therapy for the Inactivation of Candida spp. on Dentures: In Vitro Study

    OpenAIRE

    Mima, Ewerton Garcia de Oliveira; Pavarina, Ana Cláudia; Ribeiro, Daniela Garcia; Dovigo, Livia Nordi; Vergani, Carlos Eduardo; Bagnato, Vanderlei Salvador

    2011-01-01

    Objective: This in vitro study evaluated the effectiveness of photodynamic therapy (PDT) for the inactivation of different species of Candida on maxillary complete dentures. Background data: The treatment of denture stomatitis requires the inactivation of Candida spp. on dentures. PDT has been reported as an effective method for Candida inactivation. Methods: Reference strains of C. albicans, C. glabrata, C. tropicalis, C. dubliniensis and C. krusei were tested. Thirty-four dentures were fabr...

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

    OpenAIRE

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

    2016-01-01

    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 deliver...

  3. Effective near-infrared photodynamic therapy assisted by upconversion nanoparticles conjugated with photosensitizers

    Directory of Open Access Journals (Sweden)

    Dou QQ

    2015-01-01

    Full Text Available Qing Qing Dou,1 Choon Peng Teng,1 Enyi Ye,1 Xian Jun Loh1–3 1Institute of Materials Research and Engineering, A*STAR, Singapore; 2Department of Materials Science and Engineering, National University of Singapore, Singapore; 3Singapore Eye Research Institute, Singapore Abstract: A drug model photosensitizer–conjugated upconversion nanoparticles nanocomplex was explored for application in near-infrared photodynamic therapy. As near-infrared penetrates deeper into the tissue, the model is useful for the application of photodynamic therapy in deeper tissue. The nanocomplex that was synthesized had low polydispersity, and the upconversion nanoparticle was covalently conjugated with the photosensitizer. The robust bond could prevent the undesired premature release of photosensitizer and also enhance the singlet-oxygen generation. Singlet-oxygen generation rate from this nanocomplex was evaluated in solution. The photodynamic therapy effect was assessed with MCF-7 cells in two different methods, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and live/dead assay. The assay results showed that promising efficacy (>90% can be achieved with a low concentration (50 µg mL-1 of this nanocomplex and mild dosage (7 mW cm-2 of near-infrared laser treatment. Keywords: nanocomplex, singlet-oxygen generation rate, MTT assay, live/dead assay

  4. Activation of photodynamic therapy in vitro with Cerenkov luminescence generated from Yttrium-90 (Conference Presentation)

    Science.gov (United States)

    Hartl, Brad A.; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R.

    2016-03-01

    Translation of photodynamic therapy to the clinical setting has primarily been limited to easily accessible and/or superficial diseases where traditional light delivery can be performed noninvasively. Cerenkov luminescence, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively in order to overcome this depth limitation. We report on the use of Cerenkov luminescence generated from Yttrium-90 as a means to active the photodynamic therapy process in monolayer tumor cell cultures. The current study investigates the utility of Cerenkov luminescence for activating both the clinically relevant aminolevulinic acid at 1.0 mM and also the more efficient photosensitizer TPPS2a at 1.2 µM. Cells were incubated with aminolevulinic acid for 6 hours prior to radionuclide addition, as well as additional daily treatments for three days. TPPS2a was delivered as a single treatment with an 18 hour incubation time before radionuclide addition. Experiments were completed for both C6 glioma cells and MDA-MB-231 breast tumor cells. Although aminolevulinic acid proved ineffective for generating a therapeutic effect at any activity for either cell line, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 µCi/well for the C6 cell line. Current results demonstrate that it may be possible to generate a therapeutic effect in vivo using Cerenkov luminescence to activate the photodynamic therapy process with clinically relevant photosensitizers.

  5. Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia.

    Science.gov (United States)

    Kawczyk-Krupka, Aleksandra; Waśkowska, Jadwiga; Raczkowska-Siostrzonek, Agnieszka; Kościarz-Grzesiok, Anna; Kwiatek, Sebastian; Straszak, Dariusz; Latos, Wojciech; Koszowski, Rafał; Sieroń, Aleksander

    2012-06-01

    Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic. PMID:22594985

  6. Effectiveness of antimicrobial photodynamic therapy on staphylococcus aureus using phenothiazinium dye with red laser

    Science.gov (United States)

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

    2015-03-01

    The aim of this study was to evaluate in vitro the bactericidal effect of Antimicrobial Photodynamic Therapy - AmPDT using a phenothiazinium compound (toluidine blue O and methylene blue, 12.5 μg/mL) on Staphylococcus aureus (ATCC 23529) irradiated or not with the red laser (λ 660 nm, 12J/cm2). All tests were performed in triplicate and samples distributed into the following groups: Negative control, Laser, Photosensitizer, and AmPDT. Bactericidal effect of the Antimicrobial Photodynamic Therapy was assessed by counting of colony-forming units and analyzed statistically (ANOVA, Tukey test, pLaser group with Negative control, a statistically significant increase of counting on the Laser group (p = 0.003). The use of the photosensitizer alone reduced the mean number of CFU (64.8%) and its association with the Laser light resulted in 84.2% of inhibition. The results are indicative that the use of Antimicrobial Photodynamic Therapy presented in vitro bactericidal effect on Staphylococcus aureus.

  7. 131I-Zn-Chlorophyll derivative photosensitizer for tumor imaging and photodynamic therapy.

    Science.gov (United States)

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

    2015-09-30

    In recent years, the photodynamic therapy studies have gained considerable attention as an alternative method to surgery, chemotherapy and radiotherapy which is commonly used to fight cancer. In this study, biological potentials of a benzyloxy bearing zinc(II) pheophorbide-a (Zn-PH-A) were investigated via in vivo and in vitro experiments. Zn-PH-A was labeled with (131)I with high efficiency (95.3 ± 2.7%) and its biodistribution studies were investigated on female Albino Wistar rats. The radiolabeled photosensitizer had been intravenously injected into the tail vein, and then the animals were sacrificed at 30, 60 and 120 min post injection. The percent of radioactivity per gram of organs (%ID/g) was determined. The radiolabeled Zn-PH-A showed high uptake in ovary. In addition, photodynamic therapy studies of the photosensitizer were conducted in EMT6, murine mammary carcinoma and HeLa, human cervix carcinoma cell lines. For the photodynamic therapy studies, the cells with Zn-PH-A were exposed to red light (650 nm) at the doses of 10-30 J/cm(2). The results showed that Zn-PH-A has stronger PDT effect in EMT6 than HeLa cell. Our present work demonstrates (131)I-labeled photosensitizer as a bifunctional agent (PDT and nuclear imaging) which could be improved in future by using EMT6 growing tumor in nude mice.

  8. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy

    Science.gov (United States)

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24–48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  9. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy.

    Science.gov (United States)

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24-48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  10. Poly(ethylene glycol) conjugated nano-graphene oxide for photodynamic therapy

    Institute of Scientific and Technical Information of China (English)

    Pilger; FRANK

    2010-01-01

    A novel methoxy-poly(ethylene glycol) modified nano-graphene oxide(NGO-mPEG) was designed and synthesized as a photosensitizer(PS) carrier for photodynamic therapy of cancer.NGO with a size below 200 nm was prepared using a modified Hummers’ method.NGO was observed by AFM to exhibit a structure with single-layer graphene oxide sheets down to a few nanometers in height.Hydrophilic mPEG conjugation of NGO(NGO-mPEG) was found to enhance solubility in cell culture media.No apparent cytotoxicity of the NGO-mPEG was observed towards MCF-7 carcinoma cell line.Zinc phthalocyanine(ZnPc),a photosensitizer for photodynamic therapy,was loaded in the NGO-PEG through π-π stacking and hydrophobic interactions,with the drug loading efficiency up to 14 wt%.Hydrophobic ZnPc was internalized in MCF-7 cells,exhibiting a pronounced phototoxicity in the cells under Xe light irradiation.The results indicate a great potential of NGO-mPEG for photodynamic therapy of cancer.

  11. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  12. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

    Science.gov (United States)

    Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

    2015-03-01

    Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days).

  13. Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy

    Science.gov (United States)

    Zhao, Z. X.; Huang, Y. Z.; Shi, S. G.; Tang, S. H.; Li, D. H.; Chen, X. L.

    2014-07-01

    In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser.

  14. 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.

  15. The influence of photodynamic therapy on apoptosis in human melanoma cell line

    Directory of Open Access Journals (Sweden)

    T. Banas´

    2011-08-01

    Full Text Available Melanoma is the most severe of all skin cancers as it may grow rapidly and metastasize. The application of photodynamic therapy (PDT opens new perspectives in treatment of this cancer. Numerous studies suggest that the exposure of tumor cells to PDT can lead to cell death via two separate processes: apoptosis or necrosis. The aim of this study was to assess in vitro photodynamic therapy which induces apoptosis in the human Beidegröm Melanoma (BM cell line, using neutral comet assay. The cells were incubated with Photofrin II (15 μg/ml and 30 μg/ml 4 h before and 3 h after irradiation for 5 or 10 min with the light intensity of 10 mW/cm2, using a lamp with red filter (632.8 nm. The percentage of apoptotic cells was significantly higher after PDT comparing to control cells. We observed 25% and 70% of apoptotic cells after shorter irradiation and treatment with 15 μg/ml and 30 μg/ml of Ph II, respectively. After longer irradiation, the respective values were 71.9% and 90%. The results suggest that induction of apoptosis is an important determinant of photodynamic sensitivity in the studied cell line and that some types of DNA damage are dependent on photosensitizer concentration and time of irradiation.

  16. Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Ivan Mfouo-Tynga

    2015-05-01

    Full Text Available The mechanisms of cell death can be predetermined (programmed or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT uses non-toxic chemotherapeutic agents, photosensitizer (PS, to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events.

  17. Intracellular Dual Fluorescent Lightup Bioprobes for Image-Guided Photodynamic Cancer Therapy.

    Science.gov (United States)

    Han, Haijie; Jin, Qiao; Wang, Haibo; Teng, Wenzhuo; Wu, Jina; Tong, Hongxin; Chen, Tingting; Ji, Jian

    2016-07-01

    An intracellular dual fluorescent light-up bioprobe with aggregation-induced emission features and endogenously producing photosensitizer protoporphyrin IX (PpIX) abilities is designed and synthesized. The bioprobe is nonemissive in physiological environment. However, the bioprobe can selectively light up cancer cells with blue fluorescence of tetraphenylene (TPE) and red fluorescence of PpIX, owing to the release of TPE and methyl aminolevulinate after targeted internalization by cancer cells. Moreover, upon endogenous generation and accumulation of PpIX in cancer cells, efficient photodynamic ablation of cancer cells after light irradiation is demonstrated with easy regulation for optimal therapeutic efficacy. The design of such dual fluorescent light-up bioprobes might provide a new opportunity for targeted and image-guided photodynamic cancer therapy. PMID:27322139

  18. Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy.

    Science.gov (United States)

    Babii, Oleg; Afonin, Sergii; Garmanchuk, Liudmyla V; Nikulina, Viktoria V; Nikolaienko, Tetiana V; Storozhuk, Olha V; Shelest, Dmytro V; Dasyukevich, Olga I; Ostapchenko, Liudmyla I; Iurchenko, Volodymyr; Zozulya, Sergey; Ulrich, Anne S; Komarov, Igor V

    2016-04-25

    Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene-derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light-sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV-generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light. PMID:27028784

  19. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    Science.gov (United States)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  20. 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...... and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were...

  1. Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing

    Science.gov (United States)

    Wang, Xin; Liu, Kai; Yang, Guangbao; Cheng, Liang; He, Lu; Liu, Yumeng; Li, Yonggang; Guo, Liang; Liu, Zhuang

    2014-07-01

    Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via

  2. Photodynamic therapy by nonresonant two-photon excitation

    Science.gov (United States)

    Koenig, Karsten; Riemann, Iris; Fischer, Peter

    1999-07-01

    Intracellular photodynamic reactions by nonlinear excitation of porphyrin photosensitizers have been induced using near infrared ultrashort laser pulses at 200 fs pulse width, 80 MHz pulse repetition rate and 2 mW mean laser power. In particular, a highly focused 780 nm pulsed laser scanning beam was employed at a frame rate of 1/16 s-1 (60 microsecond(s) pixel dwell time) to expose Photofrin-labeled and aminolevulinic acid (ALA)-labeled Chinese hamster ovary cells. Intracellular accumulation and photobleaching of the fluorescent photosensitizers protoporphyrin IX and Photofrin have been studied by non-resonant two-photon fluorescence excitation. Subsequent scanning of the sensitizer-labeled cells resulted in reduced cloning efficiency of 50% and 0% after about 13 scans (approximately equals 10 mJ) and 50 scans, respectively, in the case of Photofrin accumulation (5 (mu) g/ml) and after about 24 scans and 100 scans in the case of ALA administration (1.5 mg/ml). Live/dead assays revealed the loss of vitality of most of cells after 50 scans for Photofrin-labeled cells and 100 scans for ALA-labeled cells. Sensitizer-free control cells could be scanned more than 250 times (1.1 h) without impact on the reproduction behavior, morphology, and vitality.

  3. Effects of fluence rate on cytoxicity during photodynamic therapy

    Science.gov (United States)

    Sitnik, Theresa M.; Henderson, Barbara W.

    1997-05-01

    Production of 1O2 during PDT may be limited as a consequence of tissue oxygen depletion by the photodynamic process. This may in turn limit cytotoxicity during PDT. One possible way of controlling oxygen consumption during treatment is through modification of fluence rate. We have studied the impact of fluence rate on tumor oxygenation and direct PDT cytotoxicity using the RIF murine tumor and the photosensitizer Photofrin. Both fluence rates caused an acute decrease in tumor pO2 to severely hypoxic levels. With 150 mW/cm2 light median pO2 remained low during prolonged exposure, while with 30 mW/cm2 light median pO2 values recovered to above control levels. When tumors treated with 135 J/cm2 at each fluence rate were tested for cell survival in a clonogenic assay, 30 mW/cm2 significantly decreased both cell clonogenicity and plating efficiency compared to light-only controls. Slight but insignificant decreases were found with 150 mW/cm2. During in vitro PDT the fluence rate of light delivery had no effect on cell survival. In summary, we have found that low fluence rate improves tumor oxygenation and direct cell effects during PDT.

  4. Pheophorbides as photosensitizers for the photodynamic therapy of tumors

    Science.gov (United States)

    Tanielian, Charles; Wolff, Christian; Kobayashi, Masami

    1995-01-01

    Quantum yields for formation of singlet molecular oxygen have been measured for sodium pheophorbides (Na-Phdes) a and b in aqueous and non-aqueous media. Measurements have been made for both steady-state and pulsed laser excitation with the resultant singlet molecular oxygen being detected by photo-oxygenation reactions or time-resolved luminescence spectroscopy, respectively. Singlet oxygen production sensitized by Na-Phdes a or b is insignificant in aqueous media but occurs with a good efficiency in organic solvents. Plasmid DNA is efficiently photocleaved by Na-Phdes a and b in the absence of oxygen as well as in the presence of oxygen. Fluorescence microscopic observation shows a rapid incorporation of Na-Phde a into nuclei, mitochondria, and lysosome of human oral mucosa cells. In contrast Na-Phde b is incorporated only into the plasma membrane. The photodynamic activity of these pigments in living tissues is probably determined by the monomeric pigment molecules formed in hydrophobic cellular structures.

  5. Photofrin-mediated photodynamic therapy for treatment of early stage laryngeal malignancies

    Directory of Open Access Journals (Sweden)

    Vanessa Gayl Schweitzer

    2011-12-01

    Full Text Available To evaluate the efficacy of PHOTOFRINmediated photodynamic therapy (PDT for the treatment of Tis-T1N0M0 squamous cell carcinoma (SqCCa of the larynx in patients not amenable to or who failed conventional head and neck treatment. This is a retrospective study of 26 patients with early stage Tis-T1 SqCCa of the larynx treated with PHOTOFRIN-mediated PDT. Intravenous PHOTOFRIN (porfimer-sodium (dose 2.0 mg/kg was administered outpatient, followed by intraoperative photoactivation at 630 nm via fiberoptic microlens surface delivery (surgical light dose 50–100 J/cm2 48–60 h later. As much as 16 out of 26 patients (62% have demonstrated complete remission (average follow-up 40 months. There were 10 patients who were noted to have partial remission with recurrence observed 2–33 months subsequently retreated with either repeated PDT therapy or conventional therapy. PHOTOFRIN-mediated photodynamic therapy can be used as a primary modality to treat Tis-T1N0M0 tumors of the larynx or for treatment for those who have failed prior surgery and/or radiation therapy. PDT allows for preservation of function and structure to maintain or improve voice with absence of systemic toxicity. Patients may have multiple drug administrations and laser light retreatment for local disease control.

  6. 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...

  7. 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...

  8. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma : a single blind, non-inferiority, randomised controlled trial

    NARCIS (Netherlands)

    Arits, Aimee H. M. M.; Mosterd, Klara; Essers, Brigitte A. B.; Spoorenberg, Eefje; Sommer, Anja; De Rooij, Michette J. M.; van Pelt, Han P. A.; Quaedvlieg, Patricia J. F.; Krekels, Gertruud A. M.; van Neer, Pierre A. F. A.; Rijzewijk, Joris J.; van Geest, Adrienne J.; Steijlen, Peter M.; Nelemans, Patty J.; Kelleners-Smeets, Nicole W. J.

    2013-01-01

    Background Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We asses

  9. 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.

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

    Science.gov (United States)

    Minamisako, Mariana Comparotto; Ribeiro, Guilherme Henrique; Lisboa, Mariáh Luz; Mariela Rodríguez Cordeiro, Mabel; Grando, Liliane Janete

    2016-01-01

    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. PMID:27668100

  11. Effect of Photodynamic Therapy with BPD-MA on the Proliferation and Apoptosis of Human Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Chuanshan Xu; Shiming Wu; Zhigang Wang; Lehua Yu; Qing Yang

    2005-01-01

    OBJECTIVE To explore the effect of photodynamic therapy with benzoporphyrin derivative monoacid ring A (BPD-MA) on the proliferation and apoptosis of human bladder cancer cells.METHODS Rhotosensitization of BPD-MA was activated with a red light laser (632.8 nm) delivered at 10 mw/cm2 to give a total dose of 2.4 J/cm2.Cellular proliferative activity was measured using the 3-(4,5-dimethylethiazil-2-yl)-2,5-Diph3-eyl tetrazolium bromide (MTT) assay and 3H-thymidine incorporation. Cell apoptosis was determined with flow cytometry analysis and the terminal deoxyuridine nicked-labeling (TUNEL) assay.RESULTS At 24 h post photodynamic treatment, photodynamic therapy significantly decreased cellular proliferative activity. The rate of apoptosis in BIU-87 cells 8 h after photodynamic treatment significantly increased up to 26.11± 2.59% as analyzed with flow cytometry. In situ labeling of DNA cleavage products with the terminal deoxyuridine nicked-labeling (TUNEL) assay reinforced these observations, BPD-MA-mediated photosensitization increased the number of TUNEL-positive cells compared to the controls. However, laser irradiation alone, BPD-MA alone and sham radiation did not affect cellular proliferative activity or apoptosis of the human bladder cancer BIU-87 cells.CONCLUSION Photodynamic therapy with BPD-MA significantly decreases cellular proliferative activity and enhances apoptosis. Therapy using this method might be a promising approach to treat patients with bladder cancer.

  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. 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.

  14. Combination of photodynamic and ultrasonic therapy for treatment of infected wounds in animal model

    Science.gov (United States)

    Menyaev, Yulian A.; Zharov, Vladimir P.

    2006-02-01

    One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40+/-20 μm wavelength of light emitting diodes (LED) array - 660+/-10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.

  15. KillerRed and miniSOG as genetically encoded photosensitizers for photodynamic therapy of cancer

    Science.gov (United States)

    Shirmanova, Marina V.; Serebrovskaya, Ekaterina O.; Snopova, Ludmila B.; Kuznetsova, Maria M.; Ryumina, Alina P.; Turchin, Ilya V.; Sergeeva, Ekaterina A.; Ignatova, Nadezhda I.; Klementieva, Natalia V.; Lukyanov, Konstantin A.; Lukyanov, Sergey A.; Zagaynova, Elena V.

    2013-06-01

    Despite of the success of photodynamic therapy (PDT) in cancer treatment, the problems of low selective accumulation of a photosensitizer in a tumor and skin phototoxicity have not resolved yet. The idea of encoding of a photosensitizer in genome of cancer cells is attractive, particularly because it can provide highly selective light induced cell killing. This work is aimed at the development of new approach to PDT of cancer, namely to using genetically encoded photosensitizers. A phototoxicity of red fluorescent GFP-like protein KillerRed and FMN-binding protein miniSOG was investigated on HeLa tumor xenografts in nude mice. The tumors were generated by subcutaneous injection of HeLa cells stably expressing the phototoxic proteins. The tumors were irradiated with 594 nm or 473 nm laser at 150 mW/cm2 for 20 or 30 min, repeatedly. Fluorescence intensity of the tumors was measured in vivo before and after each treatment procedure. Detailed pathomorphological analysis was performed 24 h after the therapy. On the epi-fluorescence images in vivo photobleaching of both proteins was observed indicating photodynamic reaction. Substantial pathomorphological abnormalities were found in the treated KillerRed-expressing tumor tissue, such as vacuolization of cytoplasm, cellular and nuclear membrane destruction, activation of apoptosis. In contrast, miniSOG-expressing tumors displayed no reaction to PDT, presumably due to the lack of FMN cofactor needed for fluorescence recovery of the flavoprotein. The results are of interest for photodynamic therapy as a proof of possibility to induce photodamages in cancer cells in vivo using genetically encoded photosensitizers.

  16. 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.

  17. Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections

    Science.gov (United States)

    Lu, Zongshun; Dai, Tianhong; Huang, Liyi; Kurup, Divya B; Tegos, George P; Jahnke, Ashlee; Wharton, Tim; Hamblin, Michael R

    2011-01-01

    Aims Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. Materials & methods We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 × 107 cells) and Pseudomonas aeruginosa (5 × 106 cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm2 of broadband white light (400–700 nm). Results In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). Conclusion These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue. PMID:21143031

  18. Photodynamic Therapy With YAG-OPO Laser for Early Stage Lung Cancer

    OpenAIRE

    Harubumi Kato; Tetsuya Okunaka; Chimori Konaka; Kiyoyuki Furuse; Yoko Kusunoki; Takeshi Horai; Nobuhide Takifuji; Syunichi Negoro; Masahiro Fukuoka; Takashi Yaya; Ichiro Kawase

    1997-01-01

    Photodynamic therapy (PDT) utilizing Photofrin is proving to be effective for the treatment of early stage lung cancers. The effect of PDT utilizing YAG-OPO laser as new light source was evaluated in 26 patients (29 lesions) with early stage lung cancers. YAG-OPO laser is solid state tunable laser which is easy to change wavelength between 620 and 670 nm exciting various kinds of photosensitizers. Moreover, YAG-OPO laser is more reliable, smaller and has less consumables than argon-dye laser ...

  19. Perspectives on the Role of Photodynamic Therapy in the Treatment of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Wei Li

    2012-01-01

    Full Text Available Photodynamic therapy (PDT is a noninvasive procedure involving a photosensitizing agent that is activated by light to produce reactive oxygen species (ROS that selectively destroy tumor cells. In recent years, PDT has been used in the treatment of pancreatic cancer (PC. The antitumor effects of PDT include three main mechanisms: direct tumor cell death (necrosis, apoptosis, and autophagy, vascular destruction, and immune system activation. The present paper systematically summarizes the effects of PDT in the treatment of PC from the experimental studies to the clinical studies and discusses the mechanisms of PDT-induced PC destruction.

  20. Optoacoustic imaging of tissue blanching during photodynamic therapy of esophageal cancer

    Science.gov (United States)

    Jacques, Steven L.; Viator, John A.; Paltauf, Guenther

    2000-05-01

    Esophageal cancer patients often present a highly inflamed esophagus at the time of treatment by photodynamic therapy. Immediately after treatment, the inflamed vessels have been shut down and the esophagus presents a white surface. Optoacoustic imaging via an optical fiber device can provide a depth profile of the blanching of inflammation. Such a profile may be an indicator of the depth of treatment achieved by the PDT. Our progress toward developing this diagnostic for use in our clinical PDT treatments of esophageal cancer patients is presented.

  1. A Clinical Study of Photodynamic Therapy for Superficial Esophageal Carcinoma by YAG-OPO Laser

    OpenAIRE

    Kazunari Yoshida; Shigeru Suzuki; Seishiro Mimura; Hiroyuki Narahara; Hiroshi Tanimura; Yugo Nagai; Kaichi Isono; Teruo Kozu; Hisayuki Fukutomi; Akira Nakahara; Hiromasa Kashimura; Toshio Hirashima; Yoko Murata; Hiroko Ide; Harubumi Kato

    1998-01-01

    A cooperative clinical study of photodynamic therapy (PDT) for superficial esophageal carcinoma was conducted at 6 medical institution. PHE (2mg/kg) with high tumor affinity was used as the oncotropic compound. The light source was a pulse wave YAG-OPO laser with high penetration into the tissue. Irradiation was performed at an energy density of 60–180 J/cm2 48–72 h after PHE administration. Eight lesions in 6 patients were treated. All were type 0-II superficial carcinomas. The depth of inva...

  2. 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.

  3. A new, efficient laser source at 630 nm for photodynamic therapy and pulsed hologram

    Energy Technology Data Exchange (ETDEWEB)

    Azzeer, Abdallah M.; Masilamani, Vadivel [King Saud University, College of Science, Riyadh (Saudi Arabia)

    2003-02-01

    This paper gives details of a new, simple and efficient laser source at 630 nm with an average power of 300 mW, based on stimulated Raman scattering (SRS) from an organic liquid, and with the second harmonic of a Nd:YAG laser as a pump source. What we have developed here can be fabricated as a module that can be added to a Nd:YAG laser, commonly available in laser clinics, for an effective photodynamic therapy (PDT) of caner. The same source would become a convenient tool for a pulsed hologram. (author)

  4. 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

    BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate....... Tumours were debulked and patients randomized to either AFXL-PDT (n = 16) or PDT (n = 16). Fractional CO2 laser treatment was applied at 5% density and 1000 μm (80 mJ) ablation depth. MAL was applied under occlusion for 3 h and illuminated with a 633-nm light-emitting diode source, 37 J cm(-2) . Clinical...

  5. Metal stenting to resolve post-photodynamic therapy stricture in early esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Young Koog Cheon

    2011-01-01

    Photodynamic therapy (PDT) is an established endoscopic technique for ablating Barrett's esophagus with high-grade dysplasia or early-stage intraepithelial neoplasia. The most common clinically significant adverse effect of PDT is esophageal stricture formation. The strictures are usually superficial and might be dilated effectively with standard endoscopic accessories, such as endoscope balloon or Savary dilators. However, multiple dilations might be required to achieve stricture resolution in some cases. We report the case of stricture that recurred after dilation with a bougie, which was completely relieved by a self-expandable metal stent.

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

    OpenAIRE

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

    2016-01-01

    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 subj...

  7. Detection techniques for singlet oxygen production during photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Li, Buhong

    2016-03-01

    Singlet oxygen is widely considered to be the major cytotoxic reactive oxygen species (ROS) generated during photodynamic therapy (PDT). This talk summarizes recent advances and future perspectives in detection techniques for singlet oxygen production, and the advantages and limitations of each technique will be presented. In addition, our custom developed novel configuration of a near-infrared sensitive camera and adaptive optics for in vivo fast imaging of singlet oxygen luminescence around 1270 nm will be highlighted. For clinical PDT application, the challenges for direct measrement of singlet oxygen luminescence will be discussed.

  8. Treatment of oral fungal infections using antimicrobial photodynamic therapy: a systematic review of currently available evidence.

    Science.gov (United States)

    Javed, Fawad; Samaranayake, Lakshman P; Romanos, Georgios E

    2014-05-01

    The aim was to review the efficacy of antimicrobial photodynamic therapy (PDT) in the treatment of oral fungal infections. To address the focused question "Should PDT be considered a possible treatment regimen for oral fungal infections?" PubMed/Medline and Google-Scholar databases were searched from 1997 up to March 2014 using various combinations of the following key words: "Candida albicans"; "Candidiasis"; "Candidosis"; "denture stomatitis"; "oral" and "photodynamic therapy". Original studies, experimental studies and articles published solely in English language were sought. Letters to the editor, historic reviews and unpublished data were excluded. Pattern of the present literature review was customized to mainly summarize the pertinent information. Fifteen studies (3 clinical and 12 experimental) were included. All studies reported antimicrobial PDT to be an effective antifungal treatment strategy. One study reported PDT and azole therapy to be equally effective in the treatment of oral fungal infections. Methylene blue, toluidine blue and porphyrin derivative were the most commonly used photosensitizers. The laser wavelengths and power output ranged between ∼455 nm-660 nm and 30 mW-400 mW. The energy fluence ranged between 26-245 J cm(-2) and the duration or irradiation ranged between 10 seconds and 26 minutes. Clinical effectiveness of antimicrobial PDT as a potent therapeutic strategy for oral fungal infections requires further investigations. PMID:24686309

  9. Photodynamic antimicrobial therapy to inhibit pseudomonas aeruginosa of corneal isolates (Conference Presentation)

    Science.gov (United States)

    Durkee, Heather A.; Relhan, Nidhi; Arboleda, Alejandro; Halili, Francisco; De Freitas, Carolina; Alawa, Karam; Aguilar, Mariela C.; Amescua, Guillermo; Miller, Darlene; Parel, Jean-Marie

    2016-03-01

    Keratitis associated with Pseudomonas aeruginosa is difficult to manage. Treatment includes antibiotic eye drops, however, some strains of Pseudomonas aeruginosa are resistant. Current research efforts are focused on finding alternative and adjunct therapies to treat multi-drug resistant bacteria. One promising alternate technique is photodynamic therapy (PDT). The purpose of this study was to evaluate the effect of riboflavin- and rose bengal-mediated PDT on Pseudomonas aeruginosa keratitis isolates in vitro. Two isolates (S+U- and S-U+) of Pseudomonas aeruginosa were derived from keratitis patients and exposed to five experimental groups: (1) Control (dark, UV-A irradiation, 525nm irradiation); (2) 0.1% riboflavin (dark, UV-A irradiation); and (3) 0.1% rose bengal, (4) 0.05% rose bengal and (5) 0.01% rose bengal (dark, 525nm irradiation). Three days after treatment, in dark conditions of all concentration of riboflavin and rose bengal showed no inhibition in both S+U- and S-U+ strains of Pseudomonas aeruginosa. In 0.1% and 0.05% rose bengal irradiated groups, for both S+U- and S-U+ strains, there was complete inhibition of bacterial growth in the central 50mm zone corresponding to the diameter of the green light source. These in vitro results suggest that rose bengal photodynamic therapy may be an effective adjunct treatment for Pseudomonas aeruginosa keratitis.

  10. 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

  11. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part five of a five-part series: ALA-PDT and MAL-PDT What Makes Them Different.

    Science.gov (United States)

    Gold, Michael H

    2009-02-01

    The use of photodynamic therapy has increased dramatically over the past several years. More clinicians are utilizing this therapy and additional indications for its use have become available. The photosensitizers that are utilized for this therapy differ and have been used differently over the past 10 years of our experience with photodynamic therapy. This manuscript examines the photosensitizers and the differences between them as well as reviews the literature on photosensitizers.

  12. Therapeutic and Aesthetic Uses of Photodynamic Therapy Part five of a five-part series: ALA–PDT and MAL–PDT What Makes Them Different

    OpenAIRE

    Gold, Michael H.

    2009-01-01

    The use of photodynamic therapy has increased dramatically over the past several years. More clinicians are utilizing this therapy and additional indications for its use have become available. The photosensitizers that are utilized for this therapy differ and have been used differently over the past 10 years of our experience with photodynamic therapy. This manuscript examines the photosensitizers and the differences between them as well as reviews the literature on photosensitizers.

  13. Photodynamic Approach for Teratoma-Free Pluripotent Stem Cell Therapy Using CDy1 and Visible Light

    Science.gov (United States)

    2016-01-01

    Pluripotent stem cells (PSC) are promising resources for regeneration therapy, but teratoma formation is one of the critical problems for safe clinical application. After differentiation, the precise detection and subsequent elimination of undifferentiated PSC is essential for teratoma-free stem cell therapy, but a practical procedure is yet to be developed. CDy1, a PSC specific fluorescent probe, was investigated for the generation of reactive oxygen species (ROS) and demonstrated to induce selective death of PSC upon visible light irradiation. Importantly, the CDy1 and/or light irradiation did not negatively affect differentiated endothelial cells. The photodynamic treatment of PSC with CDy1 and visible light irradiation confirmed the inhibition of teratoma formation in mice, and suggests a promising new approach to safe PSC-based cell therapy. PMID:27725957

  14. Influence of nitric oxide on antitumor activity of photodynamic therapy: laser systems for PDT

    Science.gov (United States)

    Evtushenko, V. A.; Zagrebelnaya, G. V.; Soldatov, Anatoly N.; Kondakova, I. V.; Shumeiko, Alexei S.

    2004-05-01

    Photodynamic therapy (PDT) is a promising therapeutic modality used for the cancer treatment. The principle of PDT is based on the formation of singlet oxygen and other activated oxygen metabolites that result in apoptotic tumor cell death. However, the resistance of some tumors to radiation therapy is recorded. The search for the chemical agents, therefore, which are able to enhance the antitumor activity of radiation therapy and induce the tumor cell apoptosis is of great importance. The use of pharmacologic agents such as donors of nitric oxide (NO) or modulators of NO-synthase may be one of the approaches to improve the therapeutic efficiency of PDT. The aim of our study was to evaluate the feasibility of using nitric oxide in combination with PDT for enhancing the induction of tumor cell apoptosis.

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

    DEFF Research Database (Denmark)

    Berking, C; Hegyi, J; Arenberger, P;

    2008-01-01

    applied photosensitizers. Illumination followed with red light-emitting diode light. RESULTS: Complete response was seen in 1/18 patients after 9 PDT cycles, and partial response in 6/18 patients (2-14 PDT cycles) giving an overall response rate of 39% (7/18). CONCLUSION: Although almost 40% of the cases......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...... showed some degree of response, PDT cannot currently be recommended as first-line therapy of NL. Subpopulations of therapy-resistant NL patients may, however, benefit from PDT....

  16. Feasibility of intrapleural photodynamic therapy: the first eight patients (Invited Paper)

    Science.gov (United States)

    Pass, Harvey I.; DeLaney, Thomas F.; Russo, Angelo; Mitchell, James; Smith, Paul D.; Friauf, Walter; Thomas, Gunter F.

    1992-06-01

    Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention being investigated for oncologic therapy. Surfaces such as the pleura or the peritoneum are frequency involved with primary or metastatic cancer, and the chance for cure in such situations is low due to the inability to eradicate all the disease. A series of investigations has been performed at the National Cancer Institute since 1985 studying the possible use of PDT for large cavity treatment. This report details the original methodology, immediate results, and overall feasibility of the delivery of intrapleural PDT to patients after debulking of primary and malignant neoplasms in the chest which were considered to be 'non-curative' by standard surgical techniques alone. From this original feasibility study, an ongoing Phase I trial has developed to determine the maximum amount of this therapy which can be delivered safely to the thorax.

  17. 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

  18. Adjustment of treatment parameters for photodynamic therapy of cervical pre-cancer and cancer

    Directory of Open Access Journals (Sweden)

    I. P. Aminodova

    2015-01-01

    Full Text Available Comprehensive study for optimization of parameters of photodynamic action with fotoditazin in patients with tumor and pre-tumor cervical diseases was conducted. The study included 52 female patients: pre-invasive cervical diseases were diagnosed in 34 (CIN I – in 9, CIN II – in 13, CIN III – in 12, cervical cancer – in 11 (8 had squamous cell cancer, 3 – adenocarcinoma of cervical canal, chronic cervicitis – in 7. The study agent in the form of 0,5% gel was applied on cervix in dose of 1 ml. To detect optimal interval between gel application and conduction of photodynamic therapy dynamics of accumulation and elimination of photosensitizer by means of its fl uorescence was studied. Fotoditazin was shown to have good accumulation in pathological tissues. The maximal agent accumulation was noticed in 30 min, continued about 15 min, and then gradually decreased. Maximal fl uorescence of photosensitizer was observed in foci of malignant tumor and severe intraepithelial neoplasia. To detect optimal light dose for irradiation cytological study of cell smear from specimen after light exposure with different light doses was performed. The minimal light dose necessary for activation of photochemical reaction pathway was 100 J/cm2, and optimal – 250 J/cm2. This dose allowed to destroy all atypical cells in the area of light exposure after application of gel fotoditazin. According to obtain data we suppose that the most effi cient regimen of photodynamic therapy with local application of fotoditazin-gel for treating dysplasia and pre-invasive cervical cancer was a dose of laser irradiation of 250 J/cm2 with duration of application of 30–45 min. 

  19. 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

  20. 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.

  1. 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.

  2. Assessing Health-Related Quality of Life with Antimicrobial Photodynamic Therapy (APDT) and Low Level Laser Therapy (LLLT) after Third Molar Removal

    OpenAIRE

    Batinjan, Goran; Filipović Zore, Irina; Rupić, Ivana; BAGO JURIČ, Ivona; Zore, Zvonimir; Gabrić Pandurić, Dragana

    2013-01-01

    Introduction: The purpose of this study was to evaluate the antimicrobial photodynamic therapy (APDT) and low level laser therapy (LLLT) on wound healing, pain intensity, swelling problems, halitosis and the postoperative usage of analgesics after surgical removal of lower third molars.

  3. Comparison of light emitting diodes and semiconductor laser inducing photodynamic therapy of cancer cells in vitro

    Science.gov (United States)

    Macecek, Jaroslav; Kolarova, Hana; Bajgar, Robert; Strnad, Miroslav

    2007-03-01

    The goal of anticancer therapy is achievement of balance between destruction of tumour cells and tissues and conservation of physiological functions of noncancer cells. Photodynamic therapy (PDT) is one of novel alternative treatment modality of malignant neoplasms. This method is based on cytotoxic action of excited sensitizers in the oxygen-rich environment. Sensitizers bound to cells and are excited by light source identical to absorption maximum of sensitizer. Photodynamic reactions lead to production of reactive oxygen species (ROS), which cause necrosis or apoptosis of cancer cells. The objective of our work was to analyse of phototoxicity in the sense of DNA damage in cancer cells after PDT by single cell gell electrophoresis (SCGE, comet assay) using ZnTPPS4 (zinc(II)-5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrine and disulfonated chloraluminium phthalocyanine ClAlPcS II as sensitizers. Violet light emitting diodes (LEDs; 1.5 mJ.cm -2.s -1; 418 nm) and semiconductor laser (50mW; 675 nm) were used as sources of radiation. Level of DNA fragmentation was detected after application of different light doses.

  4. Diacyllipid micelle-based nanocarrier for magnetically guided delivery of drugs in photodynamic therapy.

    Science.gov (United States)

    Cinteza, Ludmila O; Ohulchanskyy, Tymish Y; Sahoo, Yudhisthira; Bergey, Earl J; Pandey, Ravindra K; Prasad, Paras N

    2006-01-01

    We report the design, synthesis using nanochemistry, and characterization of a novel multifunctional polymeric micelle-based nanocarrier system, which demonstrates combined function of magnetophoretically guided drug delivery together with light-activated photodynamic therapy. Specifically, the nanocarrier consists of polymeric micelles of diacylphospholipid-poly(ethylene glycol) (PE-PEG) coloaded with the photosensitizer drug 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), and magnetic Fe3O4 nanoparticles. The nanocarrier shows excellent stability and activity over several weeks. The physicochemical characterizations have been carried out by transmission electron micrography and optical spectroscopy. An efficient cellular uptake has been confirmed with confocal laser scanning microscopy. The loading efficiency of HPPH is practically unaffected upon coloading with the magnetic nanoparticles, and its phototoxicity is retained. The magnetic response of the nanocarriers was demonstrated by their magnetically directed delivery to tumor cells in vitro. The magnetophoretic control on the cellular uptake provides enhanced imaging and phototoxicity. These multifunctional nanocarriers demonstrate the exciting prospect offered by nanochemistry for targeting photodynamic therapy.

  5. Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy

    Directory of Open Access Journals (Sweden)

    Luciana Dini

    2012-08-01

    Full Text Available Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy provides another programmed cell death pathway, known as Autophagic Cell Death (ACD. The induction of autophagy is a common outcome in PhotoDynamic Therapy (PDT, a two-step process involving the irradiation of photosensitizer (PS-loaded cancer cells. Upon tissue oxygen interaction, PS provokes immediate and direct Reactive Oxygen Species (ROS-induced damage to Endoplasmic Reticulum (ER, mitochondria, plasma membrane, and/or lysosomes. The main biological effects carried out in cancer PDT are direct cytotoxicity to tumor cells, vasculature damage and induction of inflammatory reactions stimulating immunological responses. The question about the role of autophagy in PDT and its putative immunological impact is hotly controversial and largely studied in recent times. This review deals with the induction of autophagy in PDT protocols and its dual role, also considering its interrelationship with apoptosis, the preferential cell death program triggered in the photodynamic process.

  6. Comparison of two photosensitizers in photodynamic therapy using light pulses in femtosecond regime: an animal study

    Science.gov (United States)

    Grecco, Clóvis; Pratavieira, Sebastião.; Bagnato, Vanderlei; Kurachi, Cristina

    2016-03-01

    Photodynamic therapy is a therapeutic modality for cancer treatment based on the interaction of light with a sensitizer agent and molecular oxygen present into the target cells. The aim of this study is the evaluation of photodynamic therapy using pulsed light source in the femtosecond regime through necrosis induced in healthy rat liver. The induced necrosis profile with CW laser and pulsed laser were evaluated in animal model, which received Photodithazine (chlorine e6 derivative). The light sources used in these studies were a 660 nm CW diode laser and a Ti:Sapphire Regenerative Amplifier laser (1 kHz repetition rate and 100 fs pulse width) associated with an optical parametric amplifier (OPA) to convert to 660 nm. The results were compared with a previous study when was used a hematoporphyrin derivative (Photogem) as a sensitizer. The induced necrosis with Photogen was greater with pulsed laser (2.0 +/- 0.2 mm) in comparison with CW laser (1.0 ± 0.2 mm), while in Photodithazine the induced necrosis with was greater with CW laser (2.9 +/- 0.2 mm) comparing the pulsed laser (2.0 +/- 0.2 mm). These results indicate dependence of PDT mechanisms with photosensitizer and the light regime applied.

  7. Clinical effect of photodynamic therapy on primary carious dentin after partial caries removal

    Directory of Open Access Journals (Sweden)

    Pierre Adriano Moreno NEVES

    2016-01-01

    Full Text Available Abstract This study was conducted to assess the clinical effect of photodynamic therapy (PDT in the decontamination of the deep dentin of deciduous molars submitted to partial removal of carious tissue. After cavity preparation, dentin samples were taken from the pulp wall of nineteen deciduous molars before and after PDT application. Remaining dentin was treated with 0.01% methylene blue dye followed by irradiation with an InGaAlP diode laser (λ – 660 nm; 40 mW; 120 J/cm2; 120 s. Dentin samples were microbiologically assessed for the enumeration of total microorganisms, Lactobacillus spp. and mutans streptococci. There was no significant difference in the number of colony-forming units (CFU for any of the microorganisms assessed (p > 0.05. Photodynamic therapy, using 0.01% methylene blue dye at a dosimetry of 120 J/cm2 would not be a viable clinical alternative to reduce bacterial contamination in deep dentin.

  8. Acidic Tumor pH-Responsive Nanophotomedicine for Targeted Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wooram Park

    2016-01-01

    Full Text Available An acidic tumor pH-responsive nanophotomedicine (pH-NanoPM for targeted photodynamic therapy (PDT was demonstrated herein. The pH-NanoPM was prepared with a size of ~110 nm by self-assembly of a pH-responsive polymeric photosensitizer (pH-PPS consisting of pH-cleavable methoxypolyethylene glycol (pH-C-mPEG. Because the pH-C-mPEG can be detached from the nanoparticles by hydrolysis of the benzoic-imine group at the pH of an acidic tumor (~6.5, the particle size and surface charge of the pH-NanoPM were changed along with the environmental pH condition. After detachment of the pH-C-mPEG, the pH-NanoPM particles became positively charged (+18.67±1.95 mV due to exposure of primary amine groups and decreased to a size of ~40 nm. From in vitro cellular experiments with HeLa human cervical cancer cells, the pH-NanoPM exhibited enhanced cellular internalization at acidic tumor pH compared to normal pH, which led to a significant cancer cell killing effect. These results suggest that this system has the potential to be used as a new class of nanophotomedicine for targeted photodynamic cancer therapy.

  9. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    Science.gov (United States)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  10. Determination of the optical properties of vascular tissues: potential applications in vascular-targeting photodynamic therapy

    Science.gov (United States)

    Tian, Yongbin; Chen, Ping; Lin, Lie; Huang, Zheng; Tang, Guoqing; Xu, Heping

    2007-11-01

    It has been proven that photodynamic therapy (PDT) is effective in treating various malignant and non-malignant diseases. In the treatment of certain non-malignant vascular diseases, such as wet age-related macular degeneration (AMD) and port wine stains (PWS), unlike in the treatment of malignant solid tumors, light irradiation usually starts immediately after the intravenous (IV) injection of photosensitizers while the photosensitizers is mainly circulating inside blood vessels. Under such vascular-targeting action mode, photoreactions between photosensitizers and light can selectively destruct the vascular tissues. Light distribution is complex so that it is important to understand the optical properties of targeted vessels and surrounding tissues. To better determine the optical properties of vascular tissues, we developed a tissue-simulating phantom and adopted frequency-domain measurement of phase difference. Absorption and reduced scattering coefficients in blood vessels were estimated and light distribution was simulated by the Monte Carlo method. These determinations are essential for the implication of better light dosimetry models in clinical photodynamic therapy and vascular-targeting PDT, in particular.

  11. "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

  12. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    International Nuclear Information System (INIS)

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved. (letter)

  13. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    Science.gov (United States)

    Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

    2015-03-01

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

  14. Photodynamic therapy with topical methyl- and hexylaminolevulinate for prophylaxis and treatment of UV-induced SCC in hairless mice

    DEFF Research Database (Denmark)

    Togsverd-Bo, Katrine; Lerche, Catharina M; Poulsen, Thomas;

    2010-01-01

    Hexyl aminolevulinate (HAL) is a long-chained 5-aminolevulinic acid-ester that has been proposed as a novel photosensitizing agent to methyl aminolevulinate (MAL) in topical photodynamic therapy (PDT). The more lipophilic HAL, may improve treatment outcome for non-melanoma skin cancer....

  15. Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate mediated photodynamic therapy in normal mouse skin.

    NARCIS (Netherlands)

    Bruijn, H.S. de; Haas, E.R. de; Hebeda, K.M.; Ploeg-van den Heuvel, A. van der; Sterenborg, H.J.C.M.; Neumann, H.A.; Robinson, D.J.

    2007-01-01

    Previous work demonstrated that fractionated illumination using two fractions separated by a dark interval of 2 h, significantly enhanced the clinical efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). Considering the increasing clinical use of methyl 5-aminolevulinate (MAL) an

  16. In Vivo and in Vitro Studies on the Localisation and Kinetics of Porphyrin Related Drugs for Photodetection and Photodynamic Therapy

    NARCIS (Netherlands)

    J.T.H.M. van den Akker (Johanna)

    2003-01-01

    textabstractPhotodetection and photodynamic therapy (PDT) of malignant and premalignant skin lesions are based on the activation of a photosensitive drug (photosensitiser) with (laser) light. The ideal photosensitiser accumulates selectively in the (pre)malignant tissue. Upon illumination with light

  17. Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp

    DEFF Research Database (Denmark)

    Wiegell, S.R.; Fabricius, S.; Philipsen, P.A.;

    2012-01-01

    Background: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs...... application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. Results: No difference in lesion response was found between the 11/2 and 21/2 h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75......·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between...

  18. Clinical, MRI, and histological results after photodynamic therapy of oral cancer

    Science.gov (United States)

    Herzog, Michael; Fellbaum, Ch.; Wagner-Manslau, C.; Horch, Hans-Henning

    1992-06-01

    Twenty-one carcinomas of the oral cavity in 18 patients were treated by photodynamic therapy (PDT). Patients were sensitized with Photosan III (2 mg/kg body weight), a modified HPD. Forty-eight hours after application of Photosan III, the tumor and surrounding tissues were irradiated with red laser light (200 mW/cm2, 120 J/cm2). MRI controls were carried out 24 hours after irradiation. Three to five days after irradiation, tumors were removed by conventional surgery. All specimens underwent histological examination. Histologically, hemorrhagic necroses of the irradiated tumors was found in all cases. The depth of necrosis varied from 2 to 8 mm. By MRI controls it was possible to detect edemas as change of signal resonance. PDT is a reliable therapy to reduce oral cancer selectively. Cancer destruction is limited by penetration depth of the laser light.

  19. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation

    Science.gov (United States)

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-08-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen (1O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of 1O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility.

  20. Optimization of irradiance for photodynamic therapy of port-wine stain

    Science.gov (United States)

    Zhang, Feng-juan; Hu, Xiao-ming; Zhou, Ya; Li, Qin

    2015-04-01

    Controllable and effective irradiation of lesions is among the key factors that affect the potency of photodynamic therapy (PDT). An optimization method for the irradiance distribution of treatment was proposed which can be used to improve the efficacy of PDT and allow more lesions to receive the desired irradiance level in a single therapy session. With the proposed digital illumination binocular treatment system, the preferred surface normal vectors, irradiation angles, as well as area and weight coefficients of lesions can be achieved and used as characteristic parameters to optimize the irradiation direction. Two port-wine stain phantom experiments were performed. The comparison of the illumination area between preoptimization and postoptimization showed that the proposed method can effectively guide the light source control, improve the distribution of light dose, and increase the effective treatment area.

  1. Lanthanide-doped upconversion nanoparticles electrostatically coupled with photosensitizers for near-infrared-triggered photodynamic therapy

    Science.gov (United States)

    Wang, Meng; Chen, Zhuo; Zheng, Wei; Zhu, Haomiao; Lu, Shan; Ma, En; Tu, Datao; Zhou, Shanyong; Huang, Mingdong; Chen, Xueyuan

    2014-06-01

    Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a β-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy.Lanthanide-doped upconversion nanoparticles (UCNPs) have recently shown great promise in photodynamic therapy (PDT). Herein, we report a facile strategy to fabricate an efficient NIR-triggered PDT system based on LiYF4:Yb/Er UCNPs coupled with a photosensitizer of a β-carboxyphthalocyanine zinc (ZnPc-COOH) molecule via direct electrostatic interaction. Due to the close proximity between UCNPs and ZnPc-COOH, we achieved a high energy transfer efficiency of 96.3% from UCNPs to ZnPc-COOH, which facilitates a large production of cytotoxic singlet oxygen and thus an enhanced PDT efficacy. Furthermore, we demonstrate the high efficacy of such a NIR-triggered PDT agent for the inhibition of tumor growth both in vitro and in vivo, thereby revealing the great potential of the UCNP-based PDT systems as noninvasive NIR-triggered PDT agents for deep cancer therapy. Electronic supplementary information (ESI) available: Tables S1 and S2 and Fig. S1-S13. See DOI: 10.1039/c4nr01826e

  2. Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT and Photodynamic Therapy (PDT

    Directory of Open Access Journals (Sweden)

    Miya Ishihara

    2013-06-01

    Full Text Available Applications of laser therapy, including low-level laser therapy (LLLT, phototherapy and photodynamic therapy (PDT, have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression.

  3. A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms.

    Science.gov (United States)

    George, Blassan Plackal Adimuriyil; Abrahamse, Heidi

    2016-01-01

    This review article presents an extensive examination of risk factors for breast cancer, treatment strategies with special attention to photodynamic therapy and natural product based treatments. Breast cancer remains the most commonly occurring cancer in women worldwide and the detection, treatment, and prevention are prominent concerns in public health. Background information on current developments in treatment helps to update the approach towards risk assessment. Breast cancer risk is linked to many factors such as hereditary, reproductive and lifestyle factors. Minimally invasive Photodynamic therapy (PDT) can be used in the management of various cancers; it uses a light sensitive drug (a photosensitizer, PS) and a light of visible wavelength, to destroy targeted cancer cells. State of the art analyses has been carried out to investigate advancement in the search for the cure and control of cancer progression using natural products. Traditional medicinal plants have been used as lead compounds for drug discovery in modern medicine. Both PDT and plant derived drugs induce cell death via different mechanisms including apoptosis, necrosis, autophagy, cell cycle regulation and even the regulation of various cell signalling pathways. PMID:26499768

  4. Antimicrobial Photodynamic Therapy: Study of Bacterial Recovery Viability and Potential Development of Resistance after Treatment

    Science.gov (United States)

    Tavares, Anabela; Carvalho, Carla M. B.; Faustino, Maria A.; Neves, Maria G. P. M. S.; Tomé, João P. C.; Tomé, Augusto C.; Cavaleiro, José A. S.; Cunha, Ângela; Gomes, Newton C. M.; Alves, Eliana; Almeida, Adelaide

    2010-01-01

    Antimicrobial photodynamic therapy (aPDT) has emerged in the clinical field as a potential alternative to antibiotics to treat microbial infections. No cases of microbial viability recovery or any resistance mechanisms against it are yet known. 5,10,15-tris(1-Methylpyridinium-4-yl)-20-(pentafluorophenyl)-porphyrin triiodide (Tri-Py+-Me-PF) was used as photosensitizer. Vibrio fischeri and recombinant Escherichia coli were the studied bacteria. To determine the bacterial recovery after treatment, Tri-Py+-Me-PF (5.0 μM) was added to bacterial suspensions and the samples were irradiated with white light (40 W m−2) for 270 minutes. Then, the samples were protected from light, aliquots collected at different intervals and the bioluminescence measured. To assess the development of resistance after treatment, bacterial suspensions were exposed to white light (25 minutes), in presence of 5.0 μM of Tri-Py+-Me-PF (99.99% of inactivation) and plated. After the first irradiation period, surviving colonies were collected from the plate and resuspended in PBS. Then, an identical protocol was used and repeated ten times for each bacterium. The results suggest that aPDT using Tri-Py+-Me-PF represents a promising approach to efficiently destroy bacteria since after a single treatment these microorganisms do not recover their viability and after ten generations of partially photosensitized cells neither of the bacteria develop resistance to the photodynamic process. PMID:20161973

  5. Photochemical predictive analysis of photodynamic therapy with non-homogeneous topical photosensitizer distribution in dermatological applications

    Science.gov (United States)

    Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.

    2010-04-01

    Photodynamic Therapy (PDT) is a therapeutic technique widely used in dermatology to treat several skin pathologies. It is based in topical or systemic delivery of photosensitizing drugs followed by irradiation with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell necrosis. In this work we present a PDT model that tries to predict the photodynamic effect on the skin with a topically administered photosensitizer. The time dependent inhomogeneous distribution of the photoactive compound protoporphyrin IX (PpIX) is calculated after obtaining its precursor distribution (Methyl aminolevulinate, MAL) which depends on the drug permeability, diffusion properties of the skin, incubation time and conversion efficiency of MAL to PpIX. Once the optical energy is obtained by means of the Beer Lambert law, a photochemical model is employed to estimate the concentration of the different molecular compounds taking into account the electronic transitions between molecular levels and particles concentrations. The results obtained allow us to know the evolution of the cytotoxic agent in order to estimate the necrotic area adjusting parameters such as the optical power, the photosensitizer concentration, the incubation and exposition time or the diffusivity and permeability of the tissue.

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

    International Nuclear Information System (INIS)

    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)

  7. Graphene oxide mediated delivery of methylene blue for combined photodynamic and photothermal therapy.

    Science.gov (United States)

    Sahu, Abhishek; Choi, Won Il; Lee, Jong Hyun; Tae, Giyoong

    2013-08-01

    Nano graphene oxide sheet (nanoGO) was non-covalently functionalized with Pluronic block copolymer and complexed with methylene blue, a hydrophilic and positively charged photosensitizer, via electrostatic interaction for combined photodynamic-photothermal therapy of cancer. Pluronic coating of nanoGO ensured its stability in biological fluids. NanoGO plays dual role of a photothermal material as well as a delivery agent for photosensitizer. The release of the photosensitizer from nanoGO surface was pH-dependent and an acidic condition increased the release rate considerably. This nanocomplex showed enhanced uptake by cancer cells than normal cells and in the absence of light it showed no major toxicity towards the cells. In contrast, when irradiated with selective NIR laser lights, it induced significant cell death. Intravenous injection of the complex into tumor bearing mice showed high tumor accumulation, and when the tumors were exposed to NIR lights, it caused total ablation of tumor tissue through the combined action of photodynamic and photothermal effects. This work shows the potential of nanoGO for synergistic combination phototherapy of tumor in vivo.

  8. Photosensitizer-Conjugated Human Serum Albumin Nanoparticles for Effective Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Hayoung Jeong, MyungSook Huh, So Jin Lee, Heebeom Koo, Ick Chan Kwon, Seo Young Jeong, Kwangmeyung Kim

    2011-01-01

    Full Text Available Photodynamic therapy (PDT is an emerging theranostic modality for various cancers and diseases. The focus of this study was the development of tumor-targeting albumin nanoparticles containing photosensitizers for efficient PDT. To produce tumor-targeting albumin nanoparticles, the hydrophobic photosensitizer, chlorin e6 (Ce6, was chemically conjugated to human serum albumin (HSA. The conjugates formed self-assembled nanoparticle structures with an average diameter of 88 nm under aqueous conditions. As expected, the Ce6-conjugated HSA nanoparticles (Ce6-HSA-NPs were nontoxic in their native state, but upon illumination with the appropriate wavelength of light, they produced singlet oxygen and damaged target tumor cells in a cell culture system. Importantly, when the nanoparticles were injected through the tail vein into tumor-bearing HT-29 mice, Ce6-HSA-NPs compared with free Ce6 revealed enhanced tumor-specific biodistribution and successful therapeutic results following laser irradiation. These results suggest that highly tumor-specific albumin nanoparticles have the potential to serve not only as efficient therapeutic agents, but also as photodynamic imaging (PDI reagents in cancer treatment.

  9. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. 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. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  10. 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

  11. Endoscopic laser therapy in malignant tracheobronchial obstruction using sequential Nd YAG laser and photodynamic therapy

    OpenAIRE

    Moghissi, K; Dixon, K; Hudson, E.; Stringer, M.; S. Brown

    1997-01-01

    BACKGROUND: Because the survival after treatment of advanced inoperable endo-tracheobronchial carcinoma is so poor, a pilot study was undertaken to evaluate the combined cumulative effect on survival of neodymium yttrium aluminium garnet (Nd YAG) laser followed by photodynamic treatment used endoscopically. METHODS: Seventeen patients who presented between January 1992 and March 1996 with inoperable tracheobronchial lesions causing more than 50% endoluminal obstruction were selected to ...

  12. The Effect of Photodynamic Therapy and Diode Laser as Adjunctive Periodontal Therapy on the Inflammatory Mediators Levels in Gingival Crevicular Fluid and Clinical Periodontal Status

    Science.gov (United States)

    Teymouri, Faraz; Farhad, Shirin Zahra; Golestaneh, Hedayatollah

    2016-01-01

    Statement of the Problem The presence of bacterial biofilms is the major cause of gingivitis and periodontitis, their mechanical removal is not often enough. Therefore, laser therapy and photodynamic therapy can be effective as adjunctive treatment. Purpose This study aimed to evaluate the impact of these treatments on the level of gingival crevicular fluid (GCF), inflammatory mediators, and periodontal clinical status. Materials and Method In this clinical trial, three quadrants were studied in 12 patients with chronic periodontitis aged 30-60 years. The clinical parameters were recorded and GCF samples were taken. After the first phase of periodontal treatment, one of the three quadrants was determined as the control group, one was treated by diode laser, and one underwent photodynamic therapy. The clinical parameters were recorded 2 and 6 weeks later. The data were statistically analyzed by using Friedman, ANOVA, and LSD post-test. Results Significant reduction was observed over time in the level of Interleukin-1β (IL-1β), Interleukin-17 (IL-17), clinical attachment loss, and pocket depth in the three treatment groups (plaser and photodynamic therapy significantly decreased the average bleeding on probing over time (pLaser and photodynamic therapy reduced the inflammatory mediators (IL-1β and IL-17) and improved the clinical symptoms. PMID:27602399

  13. Photodynamic therapy for malignant and non-malignant diseases: clinical investigation and application

    Institute of Scientific and Technical Information of China (English)

    QIANG Yong-gang; ZHANG Xiu-ping; LI Jian; HUANG Zheng

    2006-01-01

    @@ Photodynamic therapy (PDT) is a relatively new treatment modality. Clinical PDT procedure involves the administration of a photosensitizer followed by local illumination with visible light of a specific wavelength. In the presence of molecule oxygen, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently generate a variety of cytotoxic species.The nature, location and quantity of PDT-induced cytotoxic species and the sensitivity of the target cells determine the outcome of a PDT treatment.Since the first government approval of photosensitizer Photofrin was granted, for the treatment of bladder cancer in Canada in 1993,1 the utilization of PDT in the treatment of malignant and non-malignant diseases has increased significantly due to the improvement in photosensitizers and light applicators. Several similar photosensitizers have been developed and utilization in China since the 1980s.2

  14. Corneal heat scar caused by photodynamic therapy performed through an implanted corneal inlay.

    Science.gov (United States)

    Mita, Mariko; Kanamori, Tomomi; Tomita, Minoru

    2013-11-01

    A 60-year-old man had a combination of laser in situ keratomileusis and Kamra corneal inlay implantation to correct presbyopia. Although the outcome was favorable postoperatively, central serous chorioretinopathy was observed in the left eye along with a decrease in the uncorrected (UDVA) and corrected (CDVA) distance visual acuities and the corrected near visual acuity (CNVA). Photodynamic therapy (PDT) was later performed in a university hospital. After PDT, the patient experienced a decline in the visual acuity and came to our clinic a month after the PDT. Degeneration and a scar were observed at the location of the inlay due to the heat and burning. Flattening of the corneal topography was also observed where the corneal scar was located, along with a significant decrease in CDVA in the left eye. Prior to any surgery in which the corneal inlay is an impediment, surgeons should take advantage of the reversibility of the Kamra inlay by explanting the inlay.

  15. Photodynamic Therapy with the Silicon Phthalocyanine Pc 4 Induces Apoptosis in Mycosis Fungoides and Sezary Syndrome

    Directory of Open Access Journals (Sweden)

    Minh Lam

    2010-01-01

    Full Text Available Our current focus on the effects of Photodynamic Therapy (PDT using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF as well as Sezary syndrome (SS are variants of cutaneous T-cell lymphoma (CTCL in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4+CD7− malignant T-lymphocytes in the blood relative to CD11b+ monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2.

  16. Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review.

    Science.gov (United States)

    Magalhães, Carla M; Esteves da Silva, Joaquim C G; Pinto da Silva, Luís

    2016-08-01

    Photodynamic therapy (PDT) of cancer is known for its limited number of side effects, and requires light, oxygen and photosensitizer. However, PDT is limited by poor penetration of light into deeply localized tissues, and the use of external light sources is required. Thus, researchers have been studying ways to improve the effectiveness of this phototherapy and expand it for the treatment of the deepest cancers, by using chemiluminescent or bioluminescent formulations to excite the photosensitizer by intracellular generation of light. The aim of this Minireview is to give a précis of the most important general chemi-/bioluminescence mechanisms and to analyze several studies that apply them for PDT. These studies have demonstrated the potential of utilizing chemi-/bioluminescence as excitation source in the PDT of cancer, besides combining new approaches to overcome the limitations of this mode of treatment. PMID:27129132

  17. 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.

  18. 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.

  19. Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review.

    Science.gov (United States)

    Magalhães, Carla M; Esteves da Silva, Joaquim C G; Pinto da Silva, Luís

    2016-08-01

    Photodynamic therapy (PDT) of cancer is known for its limited number of side effects, and requires light, oxygen and photosensitizer. However, PDT is limited by poor penetration of light into deeply localized tissues, and the use of external light sources is required. Thus, researchers have been studying ways to improve the effectiveness of this phototherapy and expand it for the treatment of the deepest cancers, by using chemiluminescent or bioluminescent formulations to excite the photosensitizer by intracellular generation of light. The aim of this Minireview is to give a précis of the most important general chemi-/bioluminescence mechanisms and to analyze several studies that apply them for PDT. These studies have demonstrated the potential of utilizing chemi-/bioluminescence as excitation source in the PDT of cancer, besides combining new approaches to overcome the limitations of this mode of treatment.

  20. New approach for treatment of advanced malignant tumors: combination of chemotherapy and photodynamic therapy

    Science.gov (United States)

    Wang, Lian-xing; Ju, Hua-lamg; Chem, Zhem-ming

    1995-03-01

    Eighty-three patients suffering from moderate or advanced malignant tumors were treated by combined chemotherapy and photodynamic therapy (PDT) in our hospital. The short term result of such management is very promising, the effectiveness seems to be nearly 100% and the general responsive rate is 79.5% (CR + PR). If compared with another group of 84 similar patients whom were treated with PDT alone, the short term efficacy is 85.7% while the general response rate is 54.7% (P statistic. The better result of the combined approach is probably due to the action of the chemotherapeutic agent, potentially blocking the mitosis of the cellular cycle at certain phases of the cancer cells, making the cell membrane become more permeable to the photochemical agent, HPD, and eliciting a better cancerocidal effect.

  1. Photodynamic Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome

    Directory of Open Access Journals (Sweden)

    Sílvia Monteiro

    2014-01-01

    Full Text Available Purpose. To report the treatment outcome of photodynamic therapy with verteporfin (PDT for exudative retinal detachment (RD associated with diffuse choroidal hemangioma in Sturge-Weber syndrome (SWS. Methods. An interventional case report of a 10-year-old girl with SWS who developed an exudative RD (visual acuity hand motions that was treated with PDT. She was treated with a first session of multispot PDT. Posteriorly, a choroidotomy for drainage of subretinal fluid was created, combined with an intravitreal injection of gas (SF6 and cryoapplication. Finally, a second session of PDT was applied. Results. Subretinal fluid resolved over a period of one year and visual acuity increased to 20/125. Conclusions. PDT is an effective therapeutic option for exudative RD associated with diffuse choroidal hemangioma.

  2. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    Science.gov (United States)

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  3. Hypocrellin B doped and pH-responsive silica nanoparticles for photodynamic therapy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    pH-responsive 1O2 photosensitizing systems may serve as selective photodynamic therapy(PDT) agents by targeting the acidic interstitial fluid of many kinds of tumors.In this work,a natural and clinically used photosensitizer(Hypocrellin B,HB) and a pH indicator(Bromocresol Purple,BCP) were co-encapsulated in organically modified silica nanoparticles.BCP successfully regulated the 1O2 generation efficiency of HB through the "inner filter" effect,which shows much stronger 1O2 generation ability in an acidic than in a basic environment.In vitro experiments also demonstrated that HB-doped nanoparticles are effective in killing tumor cells by PDT.

  4. Antimicrobial Photodynamic Therapy and Dental Plaque: A Systematic Review of the Literature

    Directory of Open Access Journals (Sweden)

    G. C. Santin

    2014-01-01

    Full Text Available Background. The aim of this study was to perform a systematic review of the literature on the efficacy of antimicrobial photodynamic therapy (PDTa on cariogenic dental biofilm. Types of Studies Reviewed. Studies in vivo, in vitro, and in situ were included. Articles that did not address PDTa, those that did not involve cariogenic biofilm, those that used microorganisms in the plankton phase, and reviews were excluded. Data extraction and quality assessments were performed independently by two raters using a scale. Results. Two hundred forty articles were retrieved; only seventeen of them met the eligibility criteria and were analyzed in the present review. Considerable variability was found regarding the methodologies and application protocols for antimicrobial PDTa. Two articles reported unfavorable results. Practical Implications. The present systematic review does not allow drawing any concrete conclusions regarding the efficacy of antimicrobial PDTa, although this method seems to be a promising option.

  5. Zoon's balanitis successfully treated with photodynamic therapy: Case report and literature review.

    Science.gov (United States)

    Borgia, Francesco; Vaccaro, Mario; Foti, Antonio; Giuffrida, Roberta; Cannavò, Serafinella P

    2016-03-01

    Zoon's balanitis (ZB) is an idiopathic chronic condition usually presenting as a solitary erythematous plaque on the glans of primarily uncircumcised, middle-aged to older men. The different treatment options for this condition often achieve partial results, with frequent recurrence after treatment withdrawal. Recently, photodynamic therapy (PDT) has been proposed as therapeutic option with discordant results. We treated a thirty-five year-old man affected by Zoon's balanitis, resistant to conventional treatments, with 3 sessions of topical ALA-PDT at two weeks intervals. At the end of the treatment period notable improvement of clinical features was observed, with almost complete clearance at 3 months' follow-up, high safety profile and absence of durable side-effects. PMID:26321748

  6. Photodynamic Therapy With YAG-OPO Laser for Early Stage Lung Cancer

    Directory of Open Access Journals (Sweden)

    Harubumi Kato

    1997-01-01

    Full Text Available Photodynamic therapy (PDT utilizing Photofrin is proving to be effective for the treatment of early stage lung cancers. The effect of PDT utilizing YAG-OPO laser as new light source was evaluated in 26 patients (29 lesions with early stage lung cancers. YAG-OPO laser is solid state tunable laser which is easy to change wavelength between 620 and 670 nm exciting various kinds of photosensitizers. Moreover, YAG-OPO laser is more reliable, smaller and has less consumables than argon-dye laser or excimer-dye laser. As the result of PDT with YAG-OPO laser, complete remission (CR was obtained in 82.6% of the 29 lesions, partial remission (PR in 13.8% and no change (NC was obtained in 3.4%. We conclude that PDT utilizing YAG-OPO laser is efficacious in the treatment of early stage lung cancers and can achieve complete remission.

  7. 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.

  8. The simulation of light distribution in photodynamic therapy for port wine stains

    Science.gov (United States)

    Zhang, Shi-Yu; Hu, Xiao-Ming; Zhou, Ya

    2014-11-01

    Photodynamic Therapy is regarded as the best treatment for port wine stains, which has the main adverse effect of various degrees of pain (mild to moderate) during the illumination. Though the cooling and cold water have been used to reduce such pain, there is still no scientific evidence for these relief. In this paper, a realistic skin model is built to simulate the distribution of light under treatment, which helps control the light dose and temperature, and improve the clinical results. Comparing with the general parallel skin model, a curving stratum basale layer is used in this paper, and various blood vessel configurations such as single and multiple vessels with horizontally and vertically oriented, curve vessels, various vessel diameter and various radius of curvature of stratum basale layer are simulated. The results shows a more realistic modeling for the thermal damage and help to relief the pain in the treatment.

  9. Spectroscopical study of bacteriopurpurinimide-naphthalimide conjugates for fluorescent diagnostics and photodynamic therapy.

    Science.gov (United States)

    Panchenko, Pavel A; Sergeeva, Antonina N; Fedorova, Olga A; Fedorov, Yuri V; Reshetnikov, Roman I; Schelkunova, Anastasiya E; Grin, Mikhail A; Mironov, Andrey F; Jonusauskas, Gediminas

    2014-04-01

    Two novel bis(chromophoric) dyads ABPI-NI1 and ABPI-NI2 containing 1,8-naphthalimide and bacteriopurpurinimide units linked by p-phenylene-methylene (ABPI-NI1) and pentamethylene (ABPI-NI2) spacers were prepared to test their ability to be used in the design of effective agents for both photodynamic therapy (PDT) and fluorescent tumor imaging. Photophysical studies revealed that the emission from the naphthalimide chromophore in both conjugates was partially quenched due to resonance energy transfer between the photoactive components. Compound ABPI-NI2 with more sterically flexible oligomethylene group demonstrated higher fluorescence intensity as compared with that for ABPI-NI1. PMID:24727406

  10. Laser-triggered intraocular implant to induce photodynamic therapy for posterior capsule opacification prevention.

    Science.gov (United States)

    Zhang, Zhaoguo; Huang, Wenyong; Lei, Ming; He, Yuanfeng; Yan, Mina; Zhang, Xuefei; Zhao, Chunshun

    2016-02-10

    Posterior capsule opacification (PCO) is one of the main reasons for loss of vision again after cataract surgery. In this study, intraocular lenses were modified with indocyanine green (ICG) and sealed up with PLGA to form long-term intraocular implants (ICG-IOL). When triggered by laser, ICG-IOL would induce photodynamic therapy (PDT). In-vitro cell viability assay and scratch wound healing assay demonstrated that ICG-IOL could effectively inhibit HLEpiC proliferation and migration without causing damage to the cells far away from it. Laser attenuation test indicated that ICG-IOL could be applied in vivo. In-vivo pharmacodynamics and safety study showed that ICG-IOL could significantly prevent the occurrence of PCO and was safe for intraocular normal tissue. All these results suggested that ICG-IOL would be a very promising candidate for PCO prevention.

  11. Development and Evaluation of Nanoemulsions Containing Phthalocyanines for Use in Photodynamic Cancer Therapy.

    Science.gov (United States)

    Senna, Juliana P; Ricci-Júnior, Eduardo; Mansur, Claudia R E

    2015-06-01

    This work reports the development of oil in water (o/w) nanoemulsions containing poly(ethylene oxide)-poly(propylene oxide) block copolymer surfactant for the formulation of a delivery system for endovenous zinc and chloroaluminum phthalocyanines. A solubility study suggested clove oil and its combination with ethanol as the best candidates for the oil phase composition. The nanoemulsions were obtained using a high-pressure homogenizer and analyzed for droplet size to determine their short- and long-term stability. Formulations containing 7 and 10% oil phase and 12% surfactant presented higher stability and allowed the incorporation of a bigger amount of phthalocyanines in the formulation. Rheological analyses showed the prevailing Newtonian behavior of the nanoemulsions. Studies of toxicity and phototoxicity determined that the nanoemulsions produced were capable of inhibiting the growth of adenocarcinoma tumor cells. The nanoemulsions proved to be a good alternative for use in photodynamic therapy. PMID:26369031

  12. Improved low-power semiconductor diode lasers for photodynamic therapy in veterinary medicine

    Science.gov (United States)

    Lee, Susanne M.; Mueller, Eduard K.; Van de Workeen, Brian C.; Mueller, Otward M.

    2001-05-01

    Cryogenically cooling semiconductor diode lasers provides higher power output, longer device lifetime, and greater monochromaticity. While these effects are well known, such improvements have not been quantified, and thus cryogenically operated semiconductor lasers have not been utilized in photodynamic therapy (PDT). We report quantification of these results from laser power meter and photospectrometer data. The emission wavelengths of these low power multiple quantum well semiconductor lasers were found to decrease and become more monochromatic with decreasing temperature. Significant power output improvements also were obtained at cryogenic temperatures. In addition, the threshold current, i.e. the current at which lasing begins, decreased with decreasing temperature. This lower threshold current combined with the increased power output produced dramatically higher device efficiencies. It is proposed that cryogenic operation of semiconductor diode lasers will reduce the number of devices needed to produce the requisite output for many veterinary and medical applications, permitting significant cost reductions.

  13. 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.

  14. Assessment of anticancer effect of chlorin e6 dimethyl ether for photodynamic therapy

    Directory of Open Access Journals (Sweden)

    M. A. Kaplan

    2014-01-01

    Full Text Available Results of the study for anticancer efficacy of photodynamic therapy with chlorin e6 dimethyl ether for treatment of outbread rats with sarcoma M-1 are represented. The drug was given intravenously or intraperitonealy at a dose of 1.25 mg/kg body weight (light dose – 300 J/cm2 or 2,5 mg/kg body weight (light dose – 150 J/cm2. The spectrometry showed that maximal drug accumulation in tumor was in 2 h after intravenous injection or 3 h after intraperitoneal injection of photosensitizer, thus, sensitized tumors were irradiated according to these time intervals. Intraperitoneal injection of chlorin е6 dimethyl ether at a dose of 1.25 mg/kg body weight with treatment session in 3 h and light dose of 300 J/cm2 was the most effective (the complete response in animals – 86%.

  15. Simple Peptide-Tuned Self-Assembly of Photosensitizers towards Anticancer Photodynamic Therapy.

    Science.gov (United States)

    Liu, Kai; Xing, Ruirui; Zou, Qianli; Ma, Guanghui; Möhwald, Helmuth; Yan, Xuehai

    2016-02-24

    Peptide-tuned self-assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide- or amphiphilic amino-acid-tuned self-assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on-demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy in vitro and in vivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light. PMID:26804551

  16. Dendrimer Phthalocyanine Theranostics for Flourescence Imaging and Photodynamic Therapy of Atheromatous Plagues

    DEFF Research Database (Denmark)

    Ficker, Mario

    carried out in vitro, and in vivo studies are in progress with highly promising initial data. The dendrimer phthalocyanine nanoparticle system was nally chosen by the Consortium of the FP-7 large-scale project CosmoPHOS-nano to be translated into a clinical phase I study in human patients and is currently...... in atherosclerosis, but they cannot remove or stabilize dangerous vulnerable plaques satisfyingly. This thesis describes the development of a theranostic dendrimer-based nanoparticle system for the detection (imaging) of vulnerable atheromatous plaques and their treatment/ stabilization by means of photodynamic...... therapy. For this purpose, a dendrimer nanoparticle system was developed that showed promising cytotoxicity and immunogenicity. These dendrimers were capable of solvating lipophilic phthalocyanines, which are second-generation photosensitizers. The dendrimer phthalocyanine conjugates had light emission...

  17. Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations

    Directory of Open Access Journals (Sweden)

    Gloria Mazzone

    2016-02-01

    Full Text Available The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600–800 nm. The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenylchlorin (Foscan© already used in the photodynamic therapy (PDT protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents.

  18. Analysis of photochemical oxygen consumption effects in photodynamic therapy (Invited Paper)

    Science.gov (United States)

    Foster, Thomas H.; Gibson, Scott L.; Gao, Yongli; Hilf, Russell

    1992-06-01

    Type II photo-oxidation depends on and consumes oxygen. Several factors, including the concentration of photosensitizer and the radiation fluence rate, determine the rate of oxygen consumption in tissue undergoing Photodynamic Therapy. If the tissue capillary density is sparse, as it is in many human tumors, our calculations indicate that for cells sufficiently distant from the nearest capillary, fluence rates commonly used in PDT (50 - 200 mW/cm2) deplete 3O2 levels below those necessary for 1O2 formation. The calculations suggest that under these conditions reduced fluence rates and radiation dose fractionation should be more effective than continuous radiation at high fluence rates in producing 1O2 throughout the treated tissue volume. These predictions are supported by results obtained in vivo. The data and their interpretation have implications for PDT dosimetry and offer the possibility of improved therapeutic ratio.

  19. NIR area array CCD-based singlet oxygen luminescence imaging for photodynamic therapy

    International Nuclear Information System (INIS)

    In this work, a near-infrared CCD-based singlet oxygen luminescence two-dimensional imaging method is proposed to detect singlet oxygen by its 1270nm luminescence. Two-dimensional singlet oxygen images with its near-infrared luminescence during photosensitization could be obtained with a CCD integration time of 1s, without scanning. The data presented shows a linear relationship between the singlet oxygen luminescence intensity and sample concentration. This method provides a detection sensitivity of 0.00189mg/ml (Hematoporphyrin monomethyl Ether dissolved in ethanol) and a spatial resolution better than 100μm. We applied this method in vivo to demonstrate its potential in monitoring photodynamic therapy.

  20. The relation between methyl aminolevulinate concentration and inflammation after photodynamic therapy in healthy volunteers

    DEFF Research Database (Denmark)

    Fabricius, Susanne; Lerche, Catharina Margrethe; Philipsen, Peter Alshede;

    2013-01-01

    Inflammation and pain are well known adverse-effects in photodynamic therapy (PDT). There is currently a tendency towards introducing lower concentrations of the photosensitizer than used in the standard treatment for various indications. The aim of this study was to investigate whether reduced...... concentrations of methyl aminolevulinate (MAL) can reduce inflammation (erythema) during PDT treatment. We measured the formation of protoporphyrin IX (PpIX) using fluorescence and monitored both erythema and pain during and after PDT treatment with conventional 16% MAL and threee reduced concentrations of 2, 0.......75, and 0.25% in twenty-four healthy volunteers. We found that lowering the MAL concentration reduced PpIX fluorescence and erythema after PDT treatment. There was a strong correlation (R(2) = 0.70) between the PpIX fluorescence and erythema after treatment. A further increase in erythema after PDT...

  1. Recent Progress in Chemical Modifications of Chlorophylls and Bacteriochlorophylls for the Applications in Photodynamic Therapy.

    Science.gov (United States)

    Staron, Jakub; Boron, Bożena; Karcz, Dariusz; Szczygieł, Małgorzata; Fiedor, Leszek

    2015-01-01

    Since photodynamic therapy emerged as a promising cancer treatment, the development of photosensitizers has gained great interest. In this context, the photosynthetic pigments, chlorophylls and bacteriochlorophylls, as excellent natural photosensitizers, attracted much attention. In effect, several (bacterio) chlorophyll-based phototherapeutic agents have been developed and (or are about to) enter the clinics. The aim of this review article is to give a survey of the advances in the synthetic chemistry of these pigments which have been made over the last decade, and which are pertinent to the application of their derivatives as photosensitizers for photodynamic therapy (PDT). The review focuses on the synthetic strategies undertaken to obtain novel derivatives of (bacterio)chlorophylls with both enhanced photosensitizing and tumorlocalizing properties, and also improved photo- and chemical stability. These include modifications of the C- 17-ester moiety, the isocyclic ring, the central binding pocket, and the derivatization of peripheral functionalities at the C-3 and C-7 positions with carbohydrate-, peptide-, and nanoparticle moieties or other residues. The effects of these modifications on essential features of the pigments are discussed, such as the efficiency of reactive oxygen species generation, photostability, phototoxicity and interactions with living organisms. The review is divided into several sections. In the first part, the principles of PDT and photosensitizer action are briefly described. Then the relevant photophysical features of (bacterio)chlorophylls and earlier approaches to their modification are summarized. Next, a more detailed overview of the progress in synthetic methods is given, followed by a discussion of the effects of these modifications on the photophysics of the pigments and on their biological activity. PMID:26282940

  2. Endoscopic photodynamic therapy with hematoporphyrin derivative in the treatment of malignant tumors: report of 120 cases

    Science.gov (United States)

    Tian, Mao-en; Liu, Fa-wen; Qian, Jia-ping; Ji, Qing; Feng, Yun-qiu

    1993-03-01

    One-hundred-twenty cases of malignant tumors treated by endoscopic photodynamic therapy with hematoporphyrin derivative from August 1982 - July 1990 are reported. Of the 120 cases, including 97 males and 23 females ages varying from 39 to 77 years old, 40 cases were primary tumors and 80 cases were local residual or recurrent after surgery or radiotherapy or chemotherapy. All cases were confirmed in pathological biopsy, including 58 squamous cell carcinoma, 28 various adenocarcinoma, and 34 transitional cell carcinoma. Twenty-four, 48 and/or 72 hours after intravenous injection of HpD 2.0 - 3.0 mg/kg, or DHE 1.5 - 2.0 mg/kg, or Y-HpD 5.0 mg/kg, the tumor was irradiated with 630 nm wavelength of argon dye laser via a quartz light fiber inserted through the forceps channel of the endoscope. Of the 120 cases treated, CR was obtained in 38 cases, PR in 25 cases, MR in 52 cases, and NR in 5 cases. Total response rate was 95.8%; significant response rate 52.5%; and tumor eradicated rate 31.7%. The 38 cases included: 14 cases of early esophageal carcinoma, 3 cases of early cardiac carcinoma, 1 case of early lung cancer, 1 case of early gastric carcinoma, 15 cases of superficial bladder carcinoma, 3 cases of local residual recurrent micro lung cancer, and 1 case of cardiac carcinoma. The longest cancer-free survival was over eight years. Endoscopic photodynamic therapy is, therefore, curative effective in the treatment of early and superficial carcinoma, and palliative effective in the treatment of advanced carcinoma. Standardized and controlled trials are required to assess its place in combined treatment of malignant tumors.

  3. Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

    Science.gov (United States)

    Davidson, Sean R. H.; Weersink, Robert A.; Haider, Masoom A.; Gertner, Mark R.; Bogaards, Arjen; Giewercer, David; Scherz, Avigdor; Sherar, Michael D.; Elhilali, Mostafa; Chin, Joseph L.; Trachtenberg, John; Wilson, Brian C.

    2009-04-01

    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, D90, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D90 less than 23 J cm-2 had complete biopsy response, while 8/13 (62%) of patients with a D90 greater than 23 J cm-2 had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

  4. 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.

  5. Study of the efficacy of 5-ALA mediated photodynamic therapy on human rhabdomyosarcoma cell line (RD)

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the Rhabdomyosarcoma (RD) cell line. The present study evaluates the effects of photodynamic therapy (PDT) with 5-ALA as photosensitizer using human muscle cancer cells as experimental model. We study the photosensitizer uptake, cytotoxicity, phototoxicity, and cellular viability of the RD cells which was estimated by means of neutral-red spectrophotometric assay. The given experiment was consisted of two steps. For the first one, RD cells were exposed to 5-ALA at concentrations of 0 up to 1000 μg of ALA/ml in minimum essential medium (MEM). The optimal uptake of photosensitizer (5-ALA) in RD cells was investigated by means of spectrometric measurements. Cells viability was determined by means of neutral red assay (NRA). In the second step, 5-ALA exposed RD cells were irradiated with red light (a diode laser, λ = 635 nm) at total light dose of 80 J/cm2. The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the viability of RD cells were investigated. It was observed that sensitizer concentration or light doses have no significant effect on cells viability when studied independently. The maximal cellular uptake occurred after 47 hours in vitro incubation. The phototoxic assay showed that ALA-PDT induced killing of 76% of the cells at 250 μg/ml drug dose and 80 J/cm2 light dose

  6. Sulfonated aluminum phthalocyanines for two-photon photodynamic cancer therapy: the effect of the excitation wavelength

    International Nuclear Information System (INIS)

    Sulfonated aluminum phthalocyanine (AlPcS) is a well-studied photosensitizer which has been widely used in research and in clinical applications of the photodynamic therapy of cancers. Conventionally, one-photon excitation was used, but it was unknown whether two-photon excitation of AlPcS was equally effective. In this study, the two-photon absorption cross sections of AlPcS at near infrared wavelengths were deduced from femtosecond (fs) laser-induced fluorescence. We found that the two-photon absorption cross section of AlPcS was strongly dependent on the excitation wavelength. It was about 19 GM when excited at 800 nm, but grew to 855 GM when excited at 750 nm. The 750 nm fs-laser-induced fluorescence images of AlPcS in human nasopharyngeal carcinoma cells were clearly visible while the corresponding images were very dim when excited at 800 nm. Singlet oxygen production was 13 times higher when excited at 750 nm relative to 800 nm. Our subsequent in vitro experiments showed that 750 nm two-photon excitation with an unfocused fs laser beam damaged cancer cells in a light-dose-dependent manner typical of photodynamic therapy (PDT). The killing at 750 nm was about 9–10 times more efficient than at 800 nm. These results demonstrated for the first time that AlPcS has good potential for two-photon PDT of cancers. (paper)

  7. Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy.

    Science.gov (United States)

    Junqueira, Mariana V; Borghi-Pangoni, Fernanda B; Ferreira, Sabrina B S; Rabello, Bruno R; Hioka, Noboru; Bruschi, Marcos L

    2016-01-12

    Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 °C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future. PMID:26673856

  8. Multiple spots of photodynamic therapy for the treatment of severe chronic central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Tsakonas GD

    2012-10-01

    Full Text Available George D Tsakonas, Athanasios I Kotsolis, Chrysanthi Koutsandrea, Ilias Georgalas, Dimitrios Papakonstantinou, Ioannis D LadasFirst Department of Ophthalmology, Medical School of Athens University, Athens, GreecePurpose: To evaluate the efficacy and safety of fluorescein angiography (FA-guided photodynamic therapy (PDT for the treatment of severe chronic central serous chorioretinopathy (CSC.Methods: Patients presenting with chronic CSC with multiple areas of retinal pigment epithelium decompensation, with or without focal leaks, were treated with FA-guided full-fluence PDT. Best-corrected visual acuity (BCVA, optical coherence tomography (OCT, FA, indocyanine green angiography, and fundus autofluorescence were used to determine functional and anatomic outcomes.Results: Twenty-one eyes (17 patients were treated with PDT and followed for a median of 24 months (range, 12–73. In fourteen eyes (66.66%, two PDT spots were performed within the same session. In three eyes (14.28%, three PDT spots were performed, in two eyes (9.52% four spots, and in two eyes (9.52% five spots. In 17 eyes (80.95%, the leakage in FA and the subretinal fluid in OCT disappeared after only one session of PDT. In four eyes (19.05%, a second session – with only one spot – of PDT was required due to persistent or recurrent leakage and subfoveal SRF. Median BCVA improved significantly from 20/63 at baseline to 20/40 at 3 months (P = 0.0002 and 20/32 at 6 months (P < 0.0001, and remained improved until the last examination (20/25, P < 0.0001. Two patients complained of a transient central scotoma after the treatment.Conclusion: FA-guided full-fluence PDT with multiple PDT spots within the same session seems to be effective and safe for the treatment of chronic CSC cases with multiple areas of retinal pigment epithelium decompensation.Keywords: central serous chorioretinopathy, photodynamic therapy

  9. Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy.

    Science.gov (United States)

    Junqueira, Mariana V; Borghi-Pangoni, Fernanda B; Ferreira, Sabrina B S; Rabello, Bruno R; Hioka, Noboru; Bruschi, Marcos L

    2016-01-12

    Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 °C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future.

  10. Photodynamic Therapy

    Science.gov (United States)

    ... of cancers and pre-cancers. It has some advantages, such as: It has no long-term side ... Newer photosensitizing drugs now being studied may have advantages over the ones used today: They may be ...

  11. Prospects in the Application of Photodynamic Therapy in Oral Cancer and Premalignant Lesions.

    Science.gov (United States)

    Saini, Rajan; Lee, Nathan V; Liu, Kelly Y P; Poh, Catherine F

    2016-01-01

    Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment. PMID:27598202

  12. Targeted Multifunctional Nanoparticles cure and image Brain Tumors: Selective MRI Contrast Enhancement and Photodynamic Therapy

    Science.gov (United States)

    Kopelman, Raoul

    2008-03-01

    Aimed at targeted therapy and imaging of brain tumors, our approach uses targeted, multi-functional nano-particles (NP). A typical nano-particle contains a biologically inert, non-toxic matrix, biodegradable and bio-eliminable over a long time period. It also contains active components, such as fluorescent chemical indicators, photo-sensitizers, MRI contrast enhancement agents and optical imaging dyes. In addition, its surface contains molecular targeting units, e.g. peptides or antibodies, as well as a cloaking agent, to prevent uptake by the immune system, i.e. enabling control of the plasma residence time. These dynamic nano-platforms (DNP) contain contrast enhancement agents for the imaging (MRI, optical, photo-acoustic) of targeted locations, i.e. tumors. Added to this are targeted therapy agents, such as photosensitizers for photodynamic therapy (PDT). A simple protocol, for rats implanted with human brain cancer, consists of tail injection with DNPs, followed by 5 min red light illumination of the tumor region. It resulted in excellent cure statistics for 9L glioblastoma.

  13. Removal of black stains from teeth by photodynamic therapy: clinical and microbiological analysis.

    Science.gov (United States)

    Pessoa, Larissa; Galvão, Virgilio; Damante, Carla; Sant'Ana, Adriana Campos Passanezi

    2015-01-01

    Black-pigmented bacteria (BPB) are Gram-negative anaerobic, non-motile, proteolytic rods strongly implicated in the pathogenesis of periodontal disease. Although pigments are produced in vitro, black pigmentation is rarely found clinically. However, it may compromise aesthetics and contribute to gingival inflammation. The aim of this report is to describe a clinical case of a 10-year-old boy showing black pigmentation covering all teeth and to propose an alternative therapy for removal of black pigmentation, based on photodynamic therapy (PDT). In order to perform microbiological analysis, plaque samples were collected before and after PDT, and analysed by real-time-PCR (RT-PCR). The results showed a significant reduction in BPB levels after therapy, along with clinical evidence of absence of black pigmentation and reduction in gingival bleeding, although the plaque index remained unaltered. This case showed that PDT is effective for eliminating black pigmentation caused by BPB, without recurrence during a follow-up period of 7 months. PMID:26701991

  14. Hematoporphyrin-mediated photodynamic therapy for treatment of head and neck cancer: clinical update 1996

    Science.gov (United States)

    Schweitzer, Vanessa G.

    1996-04-01

    From 1983 to 1996 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 55 of 56 patients treated with hematoporphyrin-derivative or PHOTOFRIN-mediated photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial 'condemned mucosa' or 'field cancerization' of the oral cavity and larynx (7 cases); (2) Stage III/IV head and neck cancer (25 cases); (3) mucocutaneous AIDS-associated Kaposi's sarcoma of the upper aerodigestive tract and non AIDS-related Kaposi's sarcoma of the lower extremity (15 cases); (4) recurrent laryngotracheal papillomatosis (3 cases); (5) severe dysplasia/adenocarcinoma or squamous cell carcinoma in situ in Barrett's esophagus (4 cases); (6) partial or completely obstructing terminal esophageal cancer (9 cases). At the time of this report, HPD-PDT produced complete responses in 24 patients (follow up 6 months to 9 years) with 'field cancerization' (CIS, T1N0M0) of the oral cavity and larynx (6 cases), adenocarcinoma in situ in Barrett's esophagus (3 cases), mucocutaneous Kaposi's sarcoma (12 cases), obstructing esophageal carcinoma (1 case), and stage IV squamous cell carcinoma of the nasopharynx (1 case), and radiation therapy or solar-induced basal cell/squamous cell carcinomas (2 cases). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck cancer are reviewed in this article.

  15. Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer

    Science.gov (United States)

    Spring, Bryan; Mai, Zhiming; Rai, Prakash; Chang, Sung; Hasan, Tayyaba

    2010-02-01

    Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the "right place at the right time". This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

  16. Comparison of 5-aminolevulinic acid-encapsulated liposome versus ethosome for skin delivery for photodynamic therapy.

    Science.gov (United States)

    Fang, Yi-Ping; Tsai, Yi-Hung; Wu, Pao-Chu; Huang, Yaw-Bin

    2008-05-22

    Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for many non-melanoma skin cancers. The major limitation of this therapy, however, is the low permeability of ALA through the stratum corneum (SC) of the skin. The objective of the present work was to characterize ethosomes containing ALA and to enhance the skin production of protoporphyrin IX (PpIX), compared to traditional liposomes. Results showed that the average particle sizes of the ethosomes were less than those of liposomes. Moreover, the entrapment efficiency of ALA in the ethosome formulations was 8-66% depending on the surfactant added. The particle size of the ethosomes was still approximately ethosomes was greater than that of liposomes. The enhancements of all the formulations were ranging from 11- to 15-fold in contrast to that of control (ALA in an aqueous solution) in terms of PpIX intensity. In addition, colorimetry detected no erythema in the irradiated skin. The results demonstrated that the enhancement ratio of ethosome formulations did not significantly differ between the non-irradiated and irradiated groups except for PE/CH/SS, which may have been due to a photobleaching effect of the PDT-irradiation process. PMID:18325699

  17. Photodynamic therapy combined with distant gamma-ray therapy in the patient with squamous cell carcinoma of the skin

    Directory of Open Access Journals (Sweden)

    V. L. Filinov

    2015-01-01

    Full Text Available Results of clinical follow-up of the patient with squamous cell skin carcinoma of the nasal dorsum are represented. The patient underwent a course of combined photodynamic therapy (PDT with distant gamma-ray therapy. Distant gamma-ray therapy was performed daily during 12 days (single dose of 3 Gy, total dose of 36 Gy with the first session 24 h after injection of the photosensitization. For PDT the photosensitizer photosens at dose of 0,3 mg/kg was used. The method of prolonged PDT was applied, sessions of laser irradiation were performed daily during 7 days. The PDT sessions were carried out 2 h after session of gamma-ray therapy using distant (150 J/cm2, 40 mW/cm2 and contact (500 J/cm2, 100 mW/cm2 modalities. According to multiple cytological studies after treatment there were no signs of tumor, but inflammation. Four months after treatment according to cytological data continued tumor growth was detected. The patient underwent an additional course of PDT. Currently the patient is under follow-up: no recurrence during 8 months after repeated treatment. 

  18. Photodynamic therapy for inactivating endodontic bacterial biofilms and effect of tissue inhibitors on antibacterial efficacy

    Science.gov (United States)

    Shrestha, Annie; Kishen, Anil

    Complex nature of bacterial cell membrane and structure of biofilm has challenged the efficacy of antimicrobial photodynamic therapy (APDT) to achieve effective disinfection of infected root canals. In addition, tissue-inhibitors present inside the root canals are known to affect APDT activity. This study was aimed to assess the effect of APDT on bacterial biofilms and evaluate the effect of tissue-inhibitors on the APDT. Rose-bengal (RB) and methylene-blue (MB) were tested on Enterococcus faecalis (gram-positive) and Pseudomonas aeruginosa (gram-negative) biofilms. In vitro 7- day old biofilms were sensitized with RB and MB, and photodynamically activated with 20-60 J/cm2. Photosensitizers were pre-treated with different tissue-inhibitors (dentin, dentin-matrix, pulp tissue, bacterial lipopolysaccharides (LPS), and bovine serum albumin (BSA)) and tested for antibacterial effect of APDT. Microbiological culture based analysis was used to analyze the cell viability, while Laser Scanning Confocal Microscopy (LSCM) was used to examine the structure of biofilm. Photoactivation resulted in significant reduction of bacterial biofilms with RB and MB. The structure of biofilm under LSCM was found to be disrupted with reduced biofilm thickness. Complete biofilm elimination could not be achieved with both tested photosensitizers. APDT effect using MB and RB was inhibited in a decreasing order by dentin-matrix, BSA, pulp, dentin and LPS (Pbacterial biofilms resisted complete elimination after APDT and the tissue inhibitors existing within the root canal reduced the antibacterial activity at varying degrees. Further research is required to enhance the antibacterial efficacy of APDT in an endodontic environment.

  19. Development of therapeutic Au-methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells.

    Science.gov (United States)

    Yu, Jiashing; Hsu, Che-Hao; Huang, Chih-Chia; Chang, Po-Yang

    2015-01-14

    Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development.

  20. Three-dimensional cell culturing by magnetic levitation for evaluating efficacy/toxicity of photodynamic therapy

    Science.gov (United States)

    Sabino, Luis G.; Menezes, Priscila F. C.; Bagnato, Vanderlei S.; Souza, Glauco; Killian, Thomas C.; Kurachi, Cristina

    2014-03-01

    We used three dimensional cell cultures (3D) based on the magnetic levitation method (MLM) to evaluate cytotoxicity of photodynamic therapy (PDT). First, we decorated Hep G2 and MDA-MB-321 cells with NanoShuttle by introducing it in the media and incubated overnight. Next day, we transferred the cells to a 6-well plate and placed a magnetic driver on the top of the plate to start levitation. We monitored the formation of the 3D cell culture by optical microscopy and after four days, we added the photosensitizer Photogem (PG) in the culture media in concentrations of 50, 25, 12.5, 6.25μg/ml. We incubated them for 24 hours, after that we washed the cultures with PBS and added fresh media. Samples were then illuminated for 600s using a 630nm LED-based device, generating light intensities of 30 mW/cm2 in a total light fluence of 18 J/cm2. Following the illumination, we added fresh media, and 30 hours later, the 3D structures were broken using a pipettor and the cells seeded in 96 well plates, 105 cells per well, with a magnetic drive placed on the bottom of the plate to create cell culture dots. After 24 hours, we used a MTT assay to evaluate PDT cytotoxicity. The PDT effect, evaluated by the half maximal effective concentration (EC50), in MDA-MB-231 cells (EC50 =3.14 μg/ml) is more aggressive compared to the effect of PDT in Hep G2 cells (EC50 = 7.48 μg/ml). It suggests that the cell culture structure and its interaction facilitated the PG uptake and consequently elevated the Photodynamic effect for MDA-MB-231.

  1. Single LED-based device to perform widefield fluorescence imaging and photodynamic therapy

    Science.gov (United States)

    Grecco, Clovis; Buzzá, Hilde H.; Stringasci, Mirian D.; Andrade, Cintia T.; Vollet-Filho, Jose D.; Pratavieira, Sebastião.; Zanchin, Anderson L.; Tuboy, Aparecida M.; Bagnato, Vanderlei S.

    2015-06-01

    Photodynamic therapy (PDT) is a treatment modality that can be indicated for several cancer types and pre-cancer lesions. One of the main applications of PDT is the treatment of superficial skin lesions such as basal cell carcinoma, Bowen's disease and actinic keratosis. Three elements are necessary in PDT, a photosensitizer (PS); light at specific wavelength to be absorbed by the PS, and molecular oxygen. A typical PS used for skin lesion is protoporphyrin IX (PpIX), which is an intrinsic PS; its production is stimulated by a pro-drug, such as 5-aminolevulinic acid (ALA). Before starting a treatment, it is very important to follow up the PpIX production (to ensure that enough PS was produced prior to a PDT application) and, during a PDT session, to monitor its photodegradation (as it is evidence of the photodynamic effect taking place). The aim of this paper is to present a unique device, LINCE (MMOptics - São Carlos, Brazil), that brings together two probes that can, respectively, allow for fluorescence imaging and work as a light source for PDT treatment. The fluorescence probe of the system is optically based on 400 nm LED (light emitting diodes) arrays that allow observing the fluorescence emission over 450 nm. The PDT illumination probe options are constituted of 630 nm LED arrays for small areas and, for large areas, of both 630 nm and 450 nm LED arrays. Joining both functions at the same device makes PDT treatment simpler, properly monitorable and, hence, more clinically feasible. LINCE has been used in almost 1000 PDT treatments of superficial skin lesions in Brazil, with 88.4% of clearance of superficial BCC.

  2. Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells

    Science.gov (United States)

    Ogbodu, Racheal O.; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

    2015-02-01

    This work reports on the photodynamic therapy effect of zinc monoamino phthalocyanine linked to folic acid represented as ZnMAPc-FA, which was further immobilized onto single walled carbon nanotube represented as ZnMAPc-FA-SWCNT on melanoma A375 cell line, the effect of SWCNT-FA (without ZnMAPc) was also examined. All the compounds were non-toxic to the melanoma A375 cell line in the absence of light. Upon irradiation of the melanoma A375 cell line with a 676 nm diode laser at a power density of 98 mW/cm2 at 5 J/cm2 about 60% and 63% cell death was observed in the presence of ZnMAPc-FA and ZnMAPc-FA-SWCNT respectively. SWCNT-FA had no significant photodynamic therapy or photothermal effect to the cell, only 23% of cell death was observed after irradiation.

  3. Highly Charged Ruthenium(II) Polypyridyl Complexes as Lysosome-Localized Photosensitizers for Two-Photon Photodynamic Therapy.

    Science.gov (United States)

    Huang, Huaiyi; Yu, Bole; Zhang, Pingyu; Huang, Juanjuan; Chen, Yu; Gasser, Gilles; Ji, Liangnian; Chao, Hui

    2015-11-16

    Photodynamic therapy (PDT) is a noninvasive medical technique that has received increasing attention over the last years and been applied for the treatment of certain types of cancer. However, the currently clinically used PDT agents have several limitations, such as low water solubility, poor photostability, and limited selectivity towards cancer cells, aside from having very low two-photon cross-sections around 800 nm, which limits their potential use in TP-PDT. To tackle these drawbacks, three highly positively charged ruthenium(II) polypyridyl complexes were synthesized. These complexes selectively localize in the lysosomes, an ideal localization for PDT purposes. One of these complexes showed an impressive phototoxicity index upon irradiation at 800 nm in 3D HeLa multicellular tumor spheroids and thus holds great promise for applications in two-photon photodynamic therapy. PMID:26447888

  4. Potentiation of the Anti-Tumor Effect of Merocyanine 540-Mediated Photodynamic Therapy by Amifostine and Amphotericin B

    OpenAIRE

    Tsujino, Ichiro; Miyagi, Kiyoko; Sampson, Reynée W.; Sieber, Fritz

    2006-01-01

    Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that non-cytotoxic concentrations of amifostine (Ethyol, Ethiofos,...

  5. The application of Levulan®-based photodynamic therapy with imiquimod in the treatment of recurrent basal cell carcinoma

    OpenAIRE

    Osiecka, Beata Joanna; Jurczyszyn, Kamil; Ziółkowski, Piotr

    2012-01-01

    Summary Background Common skin tumors like basal- and squamous-cell carcinoma present a serious problem in modern medicine. Exposure to ultraviolet solar radiation is the main cause of these lesions. Since application of Aldara® and PDT separately is well documented, we decided to use both methods together. The aim of our study was to evaluate the effectiveness of local photodynamic therapy supplemented with topical application of Aldara® in basal-cell carcinoma. Material/Methods Thirty-four ...

  6. Trends in provision of photodynamic therapy and clinician attitudes: a tracker survey of a new health technology

    OpenAIRE

    Francis Jill; Foot Barny; Foy Robbie C; Chakravarthy Usha; Wormald Richard PL

    2005-01-01

    Abstract Background There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sourc...

  7. Results from phase III clinical trials with radachlorine for photodynamic therapy of pre-cancer and early cancer of cervix

    OpenAIRE

    E. V. Filonenko; L. G. Serova; V. I. Ivanova-Radkevich

    2015-01-01

    The results of clinical study for efficacy of photodynamic therapy (PDT) with radachlorine in patients with pre-cancer and cancer of cervix are represented. The study enrolled 30 patients including 4 patients with cervical erosion, 5 patients with cervical intraepithelial neoplasia II, 13 patients with cervical intraepithelial neoplasia III, 4 patients with carcinoma in situ and 4 patients with cervical cancer stage Ia. Radachlorine was administrated as single 30 minute intravenous injection ...

  8. Efficacy of red light alone and methyl-aminolaevulinate-photodynamic therapy for the treatment of mild and moderate facial acne

    OpenAIRE

    Cristian Pinto; Fabiola Schafer; Juan Jose Orellana; Sergio Gonzalez; Ariel Hasson

    2013-01-01

    Background: Photodynamic therapy (PDT) has been shown to be an effective alternative for acne. However, there is little information comparing the efficacy of red light alone and methyl aminolaevulinate (MAL)-PDT. Aims: To compare the efficacy and tolerability of red light alone and MAL-PDT in patients with mild to moderate facial acne. Methods: Thirty six patients with mild to moderate acne were enrolled. Eighteen patients recieved MAL-PDT and 18 received red light alone in two sessions, 2 we...

  9. Cooperative Clinical Trial of Photodynamic Therapy for Early Gastric Cancer With Photofrin Injection® and YAG-OPO Laser

    OpenAIRE

    Seishiro Mimura; Hiroyuki Narahara; Toshio Hirashima; Hisayuki Fukutomi; Akira Nakahara; Hiromasa Kashimura; Hirofumi Matsui; Hiroshi Tanimura; Yugo Nagai; Shigeru Suzuki; Yoko Murata; Kazunari Yoshida; Kaichi Isono; Teruo Kozu; Hiroko Ide

    1998-01-01

    Background and Objective: Photodynamic therapy (PDT) treats malignant tumors using photosensitizers and light. We employed a new pulse laser as the excitation light source for PDT, i.e. an optical parametric oscillator (OPO) system pumped by a Q-switched Nd:YAG laser, because it provides extremely high peak power. Study Design/Materials and Methods: The effects of PDT using the photosensitizer Photofrin® and the new laser were evaluated in 12 patients with early gastric cancer. Results: Compl...

  10. Magnetic resonance image-guided photodynamic therapy of xenograft pancreas tumors with verteporfin

    Science.gov (United States)

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2009-02-01

    Pancreatic cancer generally has very poor prognosis, with less than 4% survival at 5 years after diagnosis. This dismal survival rate is in part due to the aggressive nature of the adenocarcinoma, leading to a late-stage at diagnosis and exhibits resistance to most therapies. Photodynamic therapy (PDT) is a model cellular and vascular therapy agent, which uses light activation of the delivered drug to photosensitize the local cellular millieu. We suggest that interstitial verteporfin (benzoporphyrin derivative monoacid ring A) PDT has the potential to be an adjuvant therapy to the commonly used Gemcitabine chemotherapy. In the current study, an orthotopic pancreatic cancer model (Panc-1) has undergone interstitial verteporfin PDT (40 J/cm with verteporfin and 40 J/cm without verteporfin). Prior to PDT, magnetic resonance (MR) imaging was used to determine the location and size of the tumor within the pancreas, allowing accurate placement of the diffusing fiber. The success of therapy was monitored in vivo by assessing the total tumor and vascular perfusion volumes 24 hours pre- and 48 hours post-PDT. Total tumor and vascular perfusion volumes were determined using T2 weighted (T2W) and Gd-DTPA difference T1 weighted (T1W) turbo spin echo (TSE) MR imaging sequences, respectively. The validity of the in vivo imaging for therapeutic response was confirmed by ex vivo fluorescence and histological staining of frozen tissue sections. The ex vivo DiOC7(3) fluorescence analysis correlates well with the information provided from the MR images, indicating that MR imaging will be a successful surrogate marker for interstitial PDT.

  11. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    Science.gov (United States)

    de Paula, Leonardo B.; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.; Tedesco, Antonio C.

    2015-04-01

    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 (0.15×1013 or 1.50×1013 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 0.15×1013 or 1.50×1013 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.

  12. Photodynamic therapy for angiosarcoma of scalp as alternative approach for surgical treatment in patient with severe co-morbidity

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    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. 

  13. Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy

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    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.

  14. 5-aminolaevulinic Acid-photodynamic Therapy for the Treatment of Cervical Condylomata Acuminata

    Institute of Scientific and Technical Information of China (English)

    Yong-xin Liu; He-yi Zheng; Xiu-rong Liu

    2009-01-01

    Objective To investigate the efficacy and safety of photodynamic therapy(PDT)with topical 5-aminolaevulinic acid(ALA)on cervical condylomata acuminata.Methods Patients with cervical condylomata(n=30)were allocated into primary and recurrent group,and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm2 and a power of 100 mW.The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment.Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed.Results The total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up.Recurrence rate of recurrent group was significantly lower than that of prior managements(100% ,P<0.01).The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas,and was significant lower than their own control(25% vs.100% ,P<0.05).Conclusion Compared with conventional therapies,topical application of ALA-PDT is a simple,effective,safe,well-tolerated,and low recurrence rate treatment for cervical condylomata acuminata.

  15. 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.

  16. 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. 

  17. Combined Hyperthermia and Photodynamic Therapy Using a Sub-THz Gyrotron as a Radiation Source

    Science.gov (United States)

    Miyoshi, Norio; Idehara, Toshitaka; Khutoryan, Eduard; Fukunaga, Yukihiro; Bibin, Andriana Bintang; Ito, Shinji; Sabchevski, Svilen Petrov

    2016-08-01

    In this paper, we present results of a hyperthermia treatment of malignant tumors using a gyrotron as a radiation source for heating of the cancerous tissue. They clearly demonstrate the efficiency of the irradiation by sub-THz waves, which leads to steady decrease of the volume of the tumor and finally to its disappearance. A combination of hyperthermia and photodynamic therapy (PDT) that utilizes a novel multifunctional photosensitizer has also been explored. In the latter case, the results are even more convincing and promising. In particular, while after a hyperthermia treatment sometimes a regrowth of the tumor is being observed, in the case of combined hyperthermia and PDT such regrowth has never been noticed. Another combined therapy is based on a preheating of the tumor by gyrotron radiation to temperatures lower than the hyperthermia temperature of 43 °C and followed then by PDT. The results show that such combination significantly increases the efficiency of the treatment. We consider this phenomenon as a synergy effect since it is absent when hyperthermia and PDT are applied separately, and manifests itself only when both methods are combined.

  18. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

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    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.

  19. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  20. Off-label photodynamic therapy for recalcitrant facial flat warts using topical 5-aminolevulinic acid.

    Science.gov (United States)

    Yang, Ya-Li; Sang, Junjun; Liao, Ning-Xin; Wei, Fang; Liao, Wanqin; Chen, Jiang-Han

    2016-07-01

    The facial flat wart (verruca plana) is one of the most common reasons for dermatology and primary care visits. Although there are many therapeutic modalities, no single therapy has been proven to be completely curative. Case reports and uncontrolled studies suggested that photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) can effectively treat recalcitrant facial flat warts. A total of 12 patients with recalcitrant facial flat warts were enrolled in the study. ALA gel (10 %) was applied topically to lesions and incubated for 3 h. The lesions were irradiated by an LED light of 630 ± 10 nm at dose levels of 60-100 mW/cm. Clinical assessment was conducted before and after every treatment for up to 24 weeks. Among the ten patients completing three sessions of ALA-PDT, five had complete lesions clearance, and the other five patients were significantly improved. At the 24-week follow-up, the average effective rate was 88.8 %, with no recurrences. No significant side effects were reported. A low-dose topical ALA-PDT regimen using 10 % ALA, 3 h incubation, and a red light source for three treatment sessions are suggested as the optimal scheme for the treatment of recalcitrant flat warts on the face in Chinese patients. Superior efficacy is found in elevated or active period lesions with mild side effects. PMID:27059226

  1. Photodynamic Therapy in Gynecologic Malignancies: A Review of the Roswell Park Cancer Institute Experience

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    Paul C. Mayor

    2016-09-01

    Full Text Available Photodynamic therapy (PDT is a treatment modality used in the management of solid tumor malignancies that employs the use of a photosensitizing agent, a light source and oxygen in order to illicit a direct cytotoxic effect. Its use in gynecologic malignancies is somewhat novel and has been used for palliative and curative intent. At the Roswell Park Cancer Institute, the use of PDT in the management of gynecologic cancers began in the mid 1980s and since that time 35 patients have received PDT as a treatment for recurrent or metastatic cutaneous and vulvar, vaginal, anal, and cervical recurrences. In our experience, 85% patients with metastatic cutaneous lesions had a complete response. Twenty-seven percent of patients with metastatic vaginal, cervical or anal recurrences had a complete response to therapy with a median response time of 28 months. Side effects from the treatment included moderate to severe burning sensation, pain and edema at the treatment site requiring narcotic pain medication for symptom management in patients who underwent treatment to cutaneous lesions as well as lower genital tract recurrences. PDT should be considered an option in patients who are too frail to undergo the standard of care or decline the standard of care in lieu of a less invasive treatment modality.

  2. Photodynamic Therapy in Gynecologic Malignancies: A Review of the Roswell Park Cancer Institute Experience

    Science.gov (United States)

    Mayor, Paul C.; Lele, Shashikant

    2016-01-01

    Photodynamic therapy (PDT) is a treatment modality used in the management of solid tumor malignancies that employs the use of a photosensitizing agent, a light source and oxygen in order to illicit a direct cytotoxic effect. Its use in gynecologic malignancies is somewhat novel and has been used for palliative and curative intent. At the Roswell Park Cancer Institute, the use of PDT in the management of gynecologic cancers began in the mid 1980s and since that time 35 patients have received PDT as a treatment for recurrent or metastatic cutaneous and vulvar, vaginal, anal, and cervical recurrences. In our experience, 85% patients with metastatic cutaneous lesions had a complete response. Twenty-seven percent of patients with metastatic vaginal, cervical or anal recurrences had a complete response to therapy with a median response time of 28 months. Side effects from the treatment included moderate to severe burning sensation, pain and edema at the treatment site requiring narcotic pain medication for symptom management in patients who underwent treatment to cutaneous lesions as well as lower genital tract recurrences. PDT should be considered an option in patients who are too frail to undergo the standard of care or decline the standard of care in lieu of a less invasive treatment modality. PMID:27669307

  3. Photodynamic therapy--1994: treatment of benign and malignant upper aerodigestive tract disease

    Science.gov (United States)

    Schweitzer, Vanessa G.

    1995-03-01

    From 1983 to 1994 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 46 of 47 patients treated with hematoporphyrin-derivative photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial `condemned mucosa' or `field cancerization' of the oral cavity; (2) stage III/IV head and neck cancer; (3) mucocutaneous AIDS-related Kaposi's sarcoma of the upper aerodigestive tract; (4) recurrent laryngotracheal papillomatosis; (5) severe dysplasia/adenocarcinoma in situ in Barrett's esophagus; (6) partial or completely obstructing terminal esophageal cancer. HPD-PDT produced complete responses in 19 patients (follow up 6 months to 8 years) with `field cancerization' (CIS, T1) of the oral cavity and larynx (6), adenocarcinoma in situ in Barrett's esophagus (2), mucocutaneous Kaposi's sarcoma (9), obstructing esophageal carcinoma (1), and stage IV squamous cell carcinoma of the nasopharynx (1). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck disease are reviewed.

  4. Photodynamic therapy for port wine stains assisted by a novel robotic system

    Science.gov (United States)

    Huang, Naiyan; Zhu, Jianguo; Wang, Ying; Bian, Guibin; Duan, Xingguang; Liu, Weifeng; Tang, Xiaoying; Wang, Xingtao; Cui, Shihu; Zhang, Chunyu; Gu, Ying

    2010-11-01

    Port wine stains (PWS) is a vascular malformation consisting of dilated capillaries in the superficial dermis. Photodynamic therapy (PDT) is an effective approach in the treatment of PWS. However, the procedure of treatment is a low efficient and hard work, as the doctor need to hold laser fiber to irradiate for 20 min to 50 min per lesion. So an assisted novel robotic system was developed to instead part of doctor's work. The robotic system consisted of 7 degrees of freedom, in which there were 5 passive joints and 2 active joints. Binocular surveillance system was used as guidance for the robot. Clinical trial compared 20 patients (38 lesions) treated by the robotic system with another 20 patients (38 lesions) treated by a doctor. The patients in both groups were injected intravenously with photosensitizer (PSD-007, 4-5mg/kg) and irradiated with 532 nm laser (100mW/cm2, 120-300J/cm2) immediately. Both groups had same good therapeutic results. The robotic system is helpful in the PWS-PDT and hopefully would become a part of PWS therapy machine in the future.

  5. Optical spectroscopy of radiotherapy and photodynamic therapy responses in normal rat skin shows vascular breakdown products

    Science.gov (United States)

    Teles de Andrade, Cintia; Nogueira, Marcelo S.; Kanick, Stephen C.; Marra, Kayla; Gunn, Jason; Andreozzi, Jacqueline; Samkoe, Kimberley S.; Kurachi, Cristina; Pogue, Brian W.

    2016-03-01

    Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.

  6. Encapsulation of palladium porphyrin photosensitizer in layered metal oxide nanoparticles for photodynamic therapy against skin melanoma

    Science.gov (United States)

    Chen, Zih-An; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Chang, Yu-Chuan; Liu, Chen-Lun; Weng, Ching-Feng; Mou, Chung-Yuan; Lee, Chia-Hung

    2015-10-01

    We designed a biodegradable nanocarrier of layered double hydroxide (LDH) for photodynamic therapy (PDT) based on the intercalation of a palladium porphyrin photosensitizer (PdTCPP) in the gallery of LDH for melanoma theragnosis. Physical and chemical characterizations have demonstrated the photosensitizer was stable in the layered structures. In addition, the synthesized nanocomposites rendered extremely efficacious therapy in the B16F10 melanoma cell line by improving the solubility of the hydrophobic PdTCPP photosensitizer. The detection of singlet oxygen generation under irradiation at the excitation wavelength of a 532 nm laser was indeed impressive. Furthermore, the in vivo results using a tumour xenograft model in mice indicated the apparent absence of body weight loss and relative organ weight variation to the liver and kidney demonstrated that the nanocomposites were biosafe with a significant reduction in tumour volume for the anti-cancer efficacy of PDT. This drug delivery system using the nanoparticle-photosensitizer hybrid has great potential in melanoma theragnosis.

  7. Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer

    Science.gov (United States)

    Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

    1998-05-01

    Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

  8. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    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/cm2) 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/cm2) 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

  9. Monte Carlo modelling of photodynamic therapy treatments comparing clustered three dimensional tumour structures with homogeneous tissue structures

    Science.gov (United States)

    Campbell, C. L.; Wood, K.; Brown, C. T. A.; Moseley, H.

    2016-07-01

    We explore the effects of three dimensional (3D) tumour structures on depth dependent fluence rates, photodynamic doses (PDD) and fluorescence images through Monte Carlo radiation transfer modelling of photodynamic therapy. The aim with this work was to compare the commonly used uniform tumour densities with non-uniform densities to determine the importance of including 3D models in theoretical investigations. It was found that fractal 3D models resulted in deeper penetration on average of therapeutic radiation and higher PDD. An increase in effective treatment depth of 1 mm was observed for one of the investigated fractal structures, when comparing to the equivalent smooth model. Wide field fluorescence images were simulated, revealing information about the relationship between tumour structure and the appearance of the fluorescence intensity. Our models indicate that the 3D tumour structure strongly affects the spatial distribution of therapeutic light, the PDD and the wide field appearance of surface fluorescence images.

  10. The Effect of Photodynamic Therapy and Diode Laser as Adjunctive Periodontal Therapy on the Inflammatory Mediators Levels in Gingival Crevicular Fluid and Clinical Periodontal Status

    Science.gov (United States)

    Teymouri, Faraz; Farhad, Shirin Zahra; Golestaneh, Hedayatollah

    2016-01-01

    Statement of the Problem The presence of bacterial biofilms is the major cause of gingivitis and periodontitis, their mechanical removal is not often enough. Therefore, laser therapy and photodynamic therapy can be effective as adjunctive treatment. Purpose This study aimed to evaluate the impact of these treatments on the level of gingival crevicular fluid (GCF), inflammatory mediators, and periodontal clinical status. Materials and Method In this clinical trial, three quadrants were studied in 12 patients with chronic periodontitis aged 30-60 years. The clinical parameters were recorded and GCF samples were taken. After the first phase of periodontal treatment, one of the three quadrants was determined as the control group, one was treated by diode laser, and one underwent photodynamic therapy. The clinical parameters were recorded 2 and 6 weeks later. The data were statistically analyzed by using Friedman, ANOVA, and LSD post-test. Results Significant reduction was observed over time in the level of Interleukin-1β (IL-1β), Interleukin-17 (IL-17), clinical attachment loss, and pocket depth in the three treatment groups (p< 0.000). The three treatment methods significantly reduced the IL-1β and IL-17 at the baseline, up to 2 weeks, and 2-6 weeks (p< 0.05). Diode laser and photodynamic therapy significantly decreased the average bleeding on probing over time (p< 0.000 and p< 0.002, respectively). Conclusion Laser and photodynamic therapy reduced the inflammatory mediators (IL-1β and IL-17) and improved the clinical symptoms. PMID:27602399

  11. The Effect of Photodynamic Therapy and Diode Laser as Adjunctive Periodontal Therapy on the Inflammatory Mediators Levels in Gingival Crevicular Fluid and Clinical Periodontal Status

    Directory of Open Access Journals (Sweden)

    Faraz Teymouri

    2016-09-01

    Full Text Available Statement of the Problem: The presence of bacterial biofilms is the major cause of gingivitis and periodontitis, their mechanical removal is not often enough. Therefore, laser therapy and photodynamic therapy can be effective as adjunctive treatment. Purpose: This study aimed to evaluate the impact of these treatments on the level of gingival crevicular fluid (GCF, inflammatory mediators, and periodontal clinical status. Materials and Method: In this clinical trial, three quadrants were studied in 12 patients with chronic periodontitis aged 30-60 years. The clinical parameters were recorded and GCF samples were taken. After the first phase of periodontal treatment, one of the three quadrants was determined as the control group, one was treated by diode laser, and one underwent photodynamic therapy. The clinical parameters were recorded 2 and 6 weeks later. The data were statistically analyzed by using Friedman, ANOVA, and LSD post-test. Results: Significant reduction was observed over time in the level of Interleukin-1β (IL-1β, Interleukin-17 (IL-17, clinical attachment loss, and pocket depth in the three treatment groups (p< 0.000. The three treatment methods significantly reduced the IL-1β and IL-17 at the baseline, up to 2 weeks, and 2-6 weeks (p< 0.05. Diode laser and photodynamic therapy significantly decreased the average bleeding on probing over time (p< 0.000 and p< 0.002, respectively. Conclusion: Laser and photodynamic therapy reduced the inflammatory mediators (IL-1β and IL-17 and improved the clinical symptoms.

  12. Tooth color change caused by photosensitizers after photodynamic therapy: An in vitro study.

    Science.gov (United States)

    Costa, Larissa Menezes; Matos, Felipe de Souza; Correia, Ayla Macyelle de Oliveira; Carvalho, Nayane Chagas; Faria-E-Silva, André Luís; Paranhos, Luiz Renato; Ribeiro, Maria Amália Gonzaga

    2016-07-01

    This study aimed to perform an in vitro evaluation of the effect of photosensitizers used in photodynamic therapy (PDT) on tooth color change when used in combination with conventional endodontic treatment. Forty extracted human mandibular premolars were accessed and underwent root canal therapy and PDT. Photosensitizers were used in accordance with the experimental groups: MB (n=10) - PDT with Methylene Blue at 0.01%; TB (n=10) - PDT with Toluidine Blue at 0.01%; MG (n=10) - PDT with Malachite Green at 0.01%, at the concentration of 0.1mg/mL; and PC (n=10) - positive control, PDT with Endo-PTC cream stained with Methylene Blue at 25%. The samples were irradiated with 660-nm diode laser by means of a 330-μm-diameter optical fiber cable at a power density of 40mW for 120s. After light curing, the photosensitizers were removed from the specimens with 10mL sodium hypochlorite at 1%. A reflectance spectrometer was used for evaluation of color prior to and 60days after the experimental procedure based on the CIE L*a*b* system. According to ANOVA test, there were statistically significant differences between the experimental groups (p=0.003). Tukey's test showed a significant difference between PC and TB (p=0.008), as well as between MG and TB (p=0.009). However, there was no statistically significant difference between PC, MG (p=0.957) and MB (p=0.103). It was concluded that the use of PDT as an adjuvant to root canal therapy, using different photosensitizers, led to color change in tooth structure. PMID:27115871

  13. Photodynamic therapy can induce non-specific protective immunity against a bacterial infection

    Science.gov (United States)

    Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Kinoshita, Manabu; Morimoto, Yuji; Hamblin, Michael R.

    2012-03-01

    Photodynamic therapy (PDT) for cancer is known to induce an immune response against the tumor, in addition to its well-known direct cell-killing and vascular destructive effects. PDT is becoming increasingly used as a therapy for localized infections. However there has not to date been a convincing report of an immune response being generated against a microbial pathogen after PDT in an animal model. We have studied PDT as a therapy for bacterial arthritis caused by Staphylococcus aureus infection in the mouse knee. We had previously found that PDT of an infection caused by injection of MRSA (5X107 CFU) into the mouse knee followed 3 days later by 1 μg of Photofrin and 635- nm diode laser illumination with a range of fluences within 5 minutes, gave a biphasic dose response. The greatest reduction of MRSA CFU was seen with a fluence of 20 J/cm2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. We then tested the hypothesis that the host immune response mediated by neutrophils was responsible for most of the beneficial antibacterial effect. We used bioluminescence imaging of luciferase expressing bacteria to follow the progress of the infection in real time. We found similar results using intra-articular methylene blue and red light, and more importantly, that carrying out PDT of the noninfected joint and subsequently injecting bacteria after PDT led to a significant protection from infection. Taken together with substantial data from studies using blocking antibodies we believe that the pre-conditioning PDT regimen recruits and stimulates neutrophils into the infected joint which can then destroy bacteria that are subsequently injected and prevent infection.

  14. 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.

  15. Anti-tumor effects on the combination of photodynamic therapy with arsenic compound in TC-1 cells implanted C57BL/6 mice

    Science.gov (United States)

    Lee, Kyu Wan; Wen, Lan Ying; Bae, Su Mi; Park, Choong Hak; Jeon, Woo Kyu; Lee, Doo Yun; Ahn, Woong Shick

    2009-06-01

    The effects of As4O6 were studied as adjuvant on photodynamic therapy. As4O6 is considered to have anticancer activity via several biological actions such as free radical producing and inhibition of VEGF expression. In vitro experiments, cell proliferation and morphology were determined by MTT assay. Also, quantitative PCR array was performed to study the synergetic mechanism. Additionally, this study was supported by the finding that combination of photodynamic therapy and As4O6 shows an inhibition effect of tumor growth in C57BL/6 mice with TC-1 cells xenographs in vivo. Radachlorin and As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. Besides, the immunology response NEAT pathway (Ly- 12, CD178 and IL-2) also modulated after combination treatment of photodynamic therapy and As4O6. This combination effect apparently shows a same pattern in vivo model. These findings suggest the benefit of the combination treatment of photodynamic therapy and As4O6 for the inhibition of cervical cancer growth.

  16. 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.

  17. Modelling topical photodynamic therapy treatment including the continuous production of Protoporphyrin IX

    Science.gov (United States)

    Campbell, C. L.; Brown, C. T. A.; Wood, K.; Moseley, H.

    2016-11-01

    Most existing theoretical models of photodynamic therapy (PDT) assume a uniform initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX). This is an adequate assumption when the prodrug is systematically administered; however for topical PDT this is no longer a valid assumption. Topical application and subsequent diffusion of the prodrug results in an inhomogeneous distribution of PpIX, especially after short incubation times, prior to light illumination. In this work a theoretical simulation of PDT where the PpIX distribution depends on the incubation time and the treatment modality is described. Three steps of the PpIX production are considered. The first is the distribution of the topically applied prodrug, the second in the conversion from the prodrug to PpIX and the third is the light distribution which affects the PpIX distribution through photobleaching. The light distribution is modelled using a Monte Carlo radiation transfer model and indicates treatment depths of around 2 mm during daylight PDT and approximately 3 mm during conventional PDT. The results suggest that treatment depths are not only limited by the light penetration but also by the PpIX distribution.

  18. Surgery combined with topical photodynamic therapy for the treatment of squamous cell carcinoma of the lip.

    Science.gov (United States)

    Wang, Yuanyuan; Yang, Yadong; Yang, Yunchuan; Lu, Yuangang

    2016-06-01

    Due to the unique location of the squamous cell carcinoma (SCC) of the lip, using a single method such as extended resection or radiotherapy probably causes morphological and functional defects. So we used surgery combined with topical photodynamic therapy (PDT) to treat SCC of the lip. Under local anesthesia with 5% lidocaine, the hyperplastic and ulcerative SCC of the lip were curetted and assisted by topical PDTs after surgery. The 20% 5-aminolevulinic acid cream was used as a photosensitizer and applied evenly to the surface of the tumor lesion for 4h. Then the lesion site was irradiated with a 635-nm laser at 120J/cm(2). A total of five PDTs were performed postoperatively at an interval of 2 weeks. Photos were taken before and after every PDT to compare the skin lesions, treatment effects, and side effects. A long-term follow-up was undertaken to observe tumor recurrence. After surgery combined with five topical PDTs, the SCC of the lip disappeared without the compromised morphology of the lip, significant side effects, or tumor recurrence in one-year follow-up. Surgery combined with topical PDT can reduce the excision size of tumors and play a positive role in the treatment of tumors of special locations.

  19. Ultra low fluence rate photodynamic therapy: simulation of light emitted by the Cerenkov effect

    Science.gov (United States)

    Gonzales, Jonathan; Wang, Fred; Zamora, Genesis; Trinidad, Anthony; Marcu, Laura; Cherry, Simon; Hirschberg, Henry

    2014-03-01

    PDT has been shown to be most effective at low fluence rates. Many radionuclides used for both diagnostic and therapeutic purposes produce measurable amounts of visible radiation when they decay via the Cerenkov effect which occurs when a charged particle travels faster in a dielectric medium than the speed of light in that medium. Cerenkov radiation from radiopharmaceuticals could serve as a source of extended duration, low level "internal" light, to mediate PDT, with the ultimate goals of overcoming some its current limitations. Using laser light, we are exploring the effects of fluence rates that could be generated by Cerenkov radiation on PDT efficacy. ALA or TPPS2a mediated PDT of rat gliomas monolayers or multicell spheroids ( F98, C6) was performed with 410 nm laser light exposure over an extended period of 24-96hrs. Photosensitizers were delivered either as a bolus or continuously with light exposure. At fluence rate of 20μW/cm2 effective PDT was obtained as measured by decrease in cell viability or inhibition of spheroid growth. PDT is effective at ultra low fluence rates if given over long time periods. No lower threshold has been ascertained. Since the half-life of 90Y, a radionuclide with a high Cherenkov yield is 64 hrs it is a good candidate to supply sufficient light activation for PDT. The combination of radionuclide and photodynamic therapies could improve the effectiveness of cancer treatment by exploiting synergies between these two modalities.

  20. In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.

    Science.gov (United States)

    De Rosa, Fernanda Scarmato; Tedesco, Antônio Cláudio; Lopez, Renata Fonseca Vianna; Pierre, Maria Bernadete Riemma; Lange, Norbert; Marchetti, Juliana Maldonado; Rotta, Jeane Cristina Gomes; Bentley, Maria Vitória Lopes Badra

    2003-04-29

    In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT

  1. [Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy].

    Science.gov (United States)

    Deng, Chun-yue; Long, Ying-ying; Liu, Sha; Chen, Zhang-bao; Li, Chong

    2015-08-01

    In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy. PMID:26669006

  2. Photodynamic therapy with topical delta-aminolevulinic acid delays UV photocarcinogenesis in hairless mice.

    Science.gov (United States)

    Stender, I M; Bech-Thomsen, N; Poulsen, T; Wulf, H C

    1997-10-01

    Photodynamic therapy (PDT) with topical application of delta-aminolevulinic acid (ALA) followed by irradiation with visible light (ALA-PDT) is a relatively new and promising experimental treatment of superficial premalignant and malignant skin neoplasms. The purpose of this study was to determine whether ALA-PDT can prevent photocarcinogenesis in hairless mice exposed to solar UV. A total of 140 mice was divided into seven groups of 20 mice each. Group 1: solar-UV exposure. Group 2: solar UV and a cream base+visible light once a week. Group 3: solar UV and ALA-PDT once a week. Group 4: solar UV and ALA-PDT once every second week. Group 5: solar UV and ALA-PDT every fourth week. Group 6: ALA-PDT once a week. Group 7: no treatment. The time to first and to second tumor > or = 1 mm was registered. Predefined endpoints, such as one tumor > or = 4 mm or an area of small confluent tumors on the back of the mice were criteria for withdrawal from the experiment. The time to first and to second tumor was significantly longer in the ALA-PDT-treated mice than in mice only exposed to solar UV and solar-UV/cream base-visible light (P or = 4 mm (P = 0.0005). The UV unexposed mice developed no tumors. Repetitive treatments with ALA-PDT delay photoinduced carcinogenesis in mice. PMID:9337620

  3. [Procedure for daylight methyl aminolevulinate photodynamic therapy to treat actinic keratoses].

    Science.gov (United States)

    Girard, C; Adamski, H; Basset-Séguin, N; Beaulieu, P; Dreno, B; Riboulet, J-L; Lacour, J-P

    2016-04-01

    Actinic keratosis (AK), also known as solar keratosis or pre-cancerous keratosis, is frequently observed in areas of skin exposed to sunlight, particularly in light-skinned patients. In France, photodynamic therapy using red light (conventional PDT) and methylamino 5-levulinate (MAL) is indicated in the treatment of thin or non-hyperkeratotic and non-pigmented multiple AK lesions or large zones covered with AK lesions. It is well-known for its efficacy but also for its side effects, especially pain during illumination, which can limit its use. An alternative to PDT using natural daylight has recently been proposed to treat actinic keratosis lesions, and results in greater flexibility as well as significant reduction in pain. The lesions are prepared as for conventional PDT, with MAL cream being applied by the physician or the patient, after which they are exposed to natural daylight for 2hours. The lesions are then gently cleansed and protected from natural light for 24hours. This paper seeks to provide a precise description of the daylight PDT procedure for the treatment of AK. PMID:27016200

  4. Photodynamic therapy platform based on localized delivery of photosensitizer by vaterite submicron particles.

    Science.gov (United States)

    Svenskaya, Yu I; Pavlov, A M; Gorin, D A; Gould, D J; Parakhonskiy, B V; Sukhorukov, G B

    2016-10-01

    The elaboration of biocompatible and biodegradable carriers for photosensitizer targeted delivery is one of the most promising approaches in a modern photodynamic therapy (PDT). This approach is aimed at reducing sides effects connected with incidental toxicity in healthy tissue whilst also enhancing drug accumulation in the tumour area. In the present work, Photosens-loaded calcium carbonate (CaCO3) submicron particles in vaterite modification are proposed as a novel platform for anticancer PDT. Fast penetration of the carriers (0.9±0.2μm in diameter) containing 0.12% (w/w) of the photosensitizer into NIH3T3/EGFP cells is demonstrated. The captured particles provide the dye localization inside the cell increasing its local concentration, compared with "free" Photosens solution which is uniformly distributed throughout the cell. The effect of photosensitizer encapsulation into vaterite submicron particles on cell viability under laser irradiation (670nm, 19mW/cm(2), 10min) is discussed in the work. As determined by a viability assay, the encapsulation renders Photosens more phototoxic. By this means, CaCO3 carriers allow improvement of the photosensitizer effectiveness supposing, therefore, the reduction of therapeutic dose. Summation of these effects with the simplicity, upscalability and cheapness of fabrication, biocompatibility and high payload ability of the vaterite particles hold out the prospect of a novel PDT platform. PMID:27318962

  5. Photosensitizer-loaded electrospun chitosan-based scaffolds for photodynamic therapy and tissue engineering.

    Science.gov (United States)

    Severyukhina, A N; Petrova, N V; Smuda, K; Terentyuk, G S; Klebtsov, B N; Georgieva, R; Bäumler, H; Gorin, D A

    2016-08-01

    Novel chitosan-based nanofibrous composite materials containing different amounts of the photosensitizer Photosens were obtained by electrospinning and were characterized by scanning electron microscopy and by confocal laser scanning microscopy. The release of Photosens from the materials was investigated in water and in phosphate-buffered saline. A noncancerous (MC3T3-E1 murine osteoblasts) and a cancerous [T-47D (mammary gland)] cell line were cultivated on Photosens-containing scaffolds, and cell growth and metabolic activity were examined by confocal laser scanning microscopy and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide assay, respectively. The viability of both cell lines on Photosens-containing fibers decreased in a spatial manner upon laser irradiation of an appropriate wavelength and power density. Interestingly, the noncancerous MC3T3-E1 cells grown on Photosens -containing scaffolds were less affected by the irradiation. We conclude that the Photosens-containing electrospun chitosan nanofibers described here are of potential interest for biomedical applications, particularly topical photodynamic therapy and tissue engineering. PMID:27065450

  6. Glycolytic inhibitors 2-deoxyglucose and 3-bromopyruvate synergize with photodynamic therapy respectively to inhibit cell migration.

    Science.gov (United States)

    Feng, Xiaolan; Wang, Pan; Liu, Quanhong; Zhang, Ting; Mai, Bingjie; Wang, Xiaobing

    2015-06-01

    Most cancer cells have the specially increased glycolytic phenotype, which makes this pathway become an attractive therapeutic target. Although glycolytic inhibitor 2-deoxyglucose (2-DG) has been demonstrated to potentiate the cytotoxicity of photodynamic therapy (PDT), the impacts on cell migration after the combined treatment has never been reported yet. The present study aimed to analyze the influence of glycolytic inhibitors 2-DG and 3-bromopyruvate (3-BP) combined with Ce6-PDT on cell motility of Triple Negative Breast Cancer MDA-MB-231 cells. As determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium-bromide-Tetraz-olium (MTT) assay, more decreased cell viability was observed in 2-DG + PDT and 3-BP + PDT groups when compared with either monotherapy. Under optimal conditions, synergistic potentiation on cell membrane destruction and the decline of cell adhesion and cells migratory ability were observed in both 2-DG + PDT and 3-BP + PDT by electron microscope observation (SEM), wound healing and trans-well assays. Besides, serious microfilament network collapses as well as impairment of matrix metalloproteinases-9 (MMP-9) were notably improved after the combined treatments by immunofluorescent staining. These results suggest that 2-DG and 3-BP can both significantly potentiated Ce6-PDT efficacy of cell migration inhibition. PMID:25631472

  7. 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.

  8. Assessment of DNA Damage after Photodynamic Therapy Using a Metallophthalocyanine Photosensitizer

    Directory of Open Access Journals (Sweden)

    A. El-Hussein

    2012-01-01

    Full Text Available Photodynamic therapy (PDT is a chemotherapeutic approach that utilizes a bifunctional reagent, a photosensitizer (PS that localizes to the target tissue relative to the surrounding tissue and is toxic when exposed to laser light. PDT rapidly induces cell death, inflammatory and immune reactions, and damage of the microvasculature. DNA damage results from a variety of factors including UV-light, X-rays, ionizing radiation, toxins, chemicals, or reactive oxygen species. The aim of this study was to determine the effect of PDT as well as the influence of presensitization leading to the adaptive response (AR on the integrity of DNA. Lung (A549, breast (MCF-7, and esophageal (SNO cancer cells and Zn sulfophthalocyanine as PS with irradiation conditions of 10 J/cm2 at 636 nm were used. Subcellular localization of PS, cell morphology, and viability after PDT and DNA damage were determined. A significant decrease in viability and marked DNA damage was observed in all 3 cancer cell types in response to PDT while the adaptive response was demonstrated to significantly decrease the effectiveness of the PDT.

  9. 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.

  10. In vivo optical imaging to visualize photodynamic therapy-induced immune responses

    Science.gov (United States)

    Mitra, Soumya; Foster, Thomas H.

    2009-02-01

    Motivated by recent successes in growing intradermal tumors in the ears of mice and establishing the feasibility of in vivo confocal imaging of anatomic vessels in these tumors using fluorophore-conjugated antibodies to CD31, we are exploring a number of applications of optical fluorescence imaging in superficial murine tumor models in vivo. Immune responses induced by photodynamic therapy (PDT) are dynamic processes that occur in a spatially and temporally specific manner. To visualize these processes noninvasively, we have made progress in developing optical molecular imaging strategies that take advantage of intradermal injection of fluorophore-conjugated-antibodies against surface antigens on immune cells. This enables confocal imaging of the fluorescently labeled host cells to depths of at least 100 microns, and using this technique we have achieved in vivo imaging of granulocyte (GR-1)- and major histocompatibility complex class II (MHC-II)-positive cell trafficking in tumors in response to PDT. The latter include macrophages and dendritic cells. Data from tumors that were subjected to PDT with the photosensitizer, HPPH, reveals a significantly enhanced level of GR-1+ cell infiltration compared to untreated control tumor. The temporal kinetics of GR-1+ and MHC-II+ cells at different time intervals post-PDT are being examined. The ability to image host responses in vivo without excising or perturbing the tissue has opened up opportunities to explore means of optimizing them to therapeutic advantage.

  11. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    Science.gov (United States)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  12. CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

    Science.gov (United States)

    Jermyn, Michael; Davis, Scott C.; Dehghani, Hamid; Huggett, Matthew T.; Hasan, Tayyaba; Pereira, Stephen P.; Bown, Stephen G.; Pogue, Brian W.

    2014-04-01

    The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

  13. Antibacterial photodynamic therapy with 808-nm laser and indocyanine green on abrasion wound models

    Science.gov (United States)

    Topaloglu, Nermin; Güney, Melike; Yuksel, Sahru; Gülsoy, Murat

    2015-02-01

    Infections with pathogens could cause serious health problems, such as septicemia and subsequent death. Some of these deaths are caused by nosocomial, chronic, or burn-related wound infections. Photodynamic therapy (PDT) can be useful for the treatment of these infections. Our aim was to investigate the antibacterial effect of indocyanine green (ICG) and 808-nm laser on a rat abrasion wound model infected with the multidrug resistant Staphylococcus aureus strain. Abrasion wounds were infected with a multidrug resistant clinical isolate of S. aureus. ICG concentrations of 500, 1000, and 2000 μg/ml were applied with a 450 J/cm2 energy dose. Temperature change was monitored by a thermocouple system. The remaining bacterial burden was determined by the serial dilution method after each application. Wounds were observed for 11 days posttreatment. The recovery process was assessed macroscopically. Tissue samples were also examined histologically by hematoxylin-eosin staining. Around a 90% reduction in bacterial burden was observed after PDT applications. In positive control groups (ICG-only and laser-only groups), there was no significant reduction. The applied energy dose did not cause any thermal damage to the target tissue or host environment. Results showed that ICG together with a 808-nm laser might be a promising antibacterial method to eliminate infections in animals and accelerate the wound-healing process.

  14. Development of a stable solution of 5-aminolaevulinic acid for intracutaneous injection in photodynamic therapy.

    Science.gov (United States)

    de Blois, A W; Grouls, R J E; Ackerman, E W; Wijdeven, W J A

    2002-01-01

    Photodynamic therapy using 5-aminolaevulinic acid (ALA) as a photosensitiser is a new treatment modality for basal cell carcinomas. Until now ALA has been used topically as a cream. As this administration route leads sometimes to insufficient penetration in the skin, an intracutaneously injectable solution of ALA was developed. The influence of pH, concentration and temperature on the degradation of ALA in aqueous solution was investigated in order to optimise the formulation of the injection. In 0.1% ALA solutions with pH values between 4 and 8 a pH dependency of ALA degradation was shown, comprising fast decomposition at pH values higher than 7, whereas at a pH value of 6 or lower the solutions remained within the range of 90-110% of the initial concentration for at least 128 days. An increase of degradation rate with increasing concentrations became evident which is consistent with the supposed second-order degradation kinetics. After accelerated stability research at 63 degrees C and 85 degrees C a shelf life of 281 days for a 0.1% ALA solution pH 5 was calculated from an Arrhenius plot. A 2% ALA solution was proven to be isotonic. From our results a 0.1-2% ALA solution with pH 5 and an appropriate amount of sodium chloride to obtain isotonicity is recommended as an injectable solution. PMID:12181635

  15. Acne treatment by methyl aminolevulinate photodynamic therapy with red light vs. intense pulsed light.

    Science.gov (United States)

    Hong, Jong Soo; Jung, Jae Yoon; Yoon, Ji Young; Suh, Dae Hun

    2013-05-01

    Various methods of photodynamic therapy (PDT) for acne have been introduced. However, comparative studies among them are still needed. We performed this study to compare the effect of methyl aminolevulinate (MAL) PDT for acne between red light and intense pulsed light (IPL). Twenty patients were enrolled in this eight-week, prospective, split-face study. We applied MAL cream over the whole face with a three-hour incubation time. Then patients were irradiated with 22 J/cm(2) of red light on one-half of the face and 8-10 J/cm(2) of IPL on the other half during each treatment session. We performed three treatment sessions at two-week intervals and followed-up patients until four weeks after the last session. Inflammatory and non-inflammatory acne lesions were reduced significantly on both sides. The red light side showed a better response than the IPL side after the first treatment. Serious adverse effects after treatment were not observed. MAL-PDT with red light and IPL are both an effective and safe modality in acne treatment. Red light showed a faster response time than IPL. After multiple sessions, both light sources demonstrated satisfactory results. We suggest that reducing the total dose of red light is desirable when performing MAL-PDT in Asian patients with acne compared with Caucasians.

  16. Pseudoepitheliomatous Hyperplasia Treated by Photodynamic Therapy with Variable Irradiation Dose and Concentration of Photosensitizer

    Science.gov (United States)

    Jiao, Bin; Long, Heather Ann

    2011-01-01

    Abstract Objective: The aim of this study was to test the effectiveness of photodynamic therapy (PDT) in treating pseudoepitheliomatous hyperplasia (PEH) after skin wounding. Background Data: PEH is a difficult-to-treat extreme-degree acanthosis characterized by proliferation of the epithelium. Topical PDT offers an effective and non-invasive treatment for intraepithelial neoplasia and inflammatory dermatosis. These disorders and PEH show the same histological features: epidermal hyperplasia. To our knowledge, there have been no clinical trials published about therapeutic responses of PDT for PEH. Materials and Methods: After application of 10–30% methyl aminolaevulinate (MAL) emulsion, each lesion was irradiated with 633-nm red light at a total dose of 113–339 J/cm2. Therapeutic response was assessed by clinical examination at 3 months. Results: Only 4 of 16 lesions clinically showed a minimal response. No response was observed in 12 of the 16 lesions, either with different cumulative doses or different concentrations of MAL. Conclusion: PEH after skin wounding responds poorly to the topical MAL-PDT. Besides removal of underlying diseases, surgical excision is still the recommended first option. PMID:20969441

  17. Fluorescence Diagnosis of Damage to Tumor Tissues During Photodynamic Therapy with the Photosensitizer Photolon®

    Science.gov (United States)

    Samtsov, M. P.; Tarasau, D. S.; Kaplevsky, K. N.; Voropay, E. S.; Petrov, P. T.; Istomin, Yu. P.

    2016-03-01

    We have studied the feasibility of using an indotricarbocyanine dye as a marker for the efficacy of photodynamic therapy (PDT) of cancers with the photosensitizer Photolon®. We have established that on exposure to laser emission at λ = 667 nm with an exposure dose of 100 J/cm2, we observe that the Photolon® concentration drops by about a factor of two in the exposed part of the tumor, while the concentration of the indotricarbocyanine dye does not change in any region of the tumor node. We have observed a correlation between the change in the shape of the fluorescence spectra of the indotricarbocyanine dye in vivo in the 780-880 nm resulting from a PDT session with the photosensitizer Photolon® and the extent of damage to the tumor tissues. Changes in the shape of the fluorescence spectrum of the dye are interpreted in terms of a model involving the appearance of absorption by different forms of hemoglobin, and changes in their ratio in the exposed part of the tumor due to consumption of molecular oxygen.

  18. 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.

  19. Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

    Science.gov (United States)

    Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

    2016-07-01

    The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

  20. Activating Photodynamic Therapy in vitro with Cerenkov Radiation Generated from Yttrium-90.

    Science.gov (United States)

    Hartl, Brad A; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R

    2016-01-01

    The translation of photodynamic therapy (PDT) to the clinical setting has primarily been limited to easily accessible and/or superficial diseases, for which traditional light delivery can be performed noninvasively. Cerenkov radiation, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively to overcome this depth limitation. This article investigates the utility of Cerenkov radiation, as generated from the radionuclide yttrium-90, for activating the PDT process using clinically approved aminolevulinic acid at 1.0 mm and also the more efficient porphyrin-based photosensitizer mesotetraphenylporphine with two sulfonate groups on adjacent phenyl rings (TPPS2a) at 1.2 µm. Experiments were conducted with monolayer cultured glioma and breast tumor cell lines. Although aminolevulinic acid proved to be ineffective for generating a therapeutic effect at all but the highest activity levels, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 µCi/well for the C6 glioma cell line. Importantly, these results demonstrate for the first time, to our knowledge, that Cerenkov radiation generated from a radionuclide can be used to activate PDT using clinically relevant photosensitizers. These results therefore provide evidence that it may be possible to generate a phototherapeutic effect in vivo using Cerenkov radiation and clinically relevant photosensitizers. PMID:27481495

  1. Patients' perceptions of antimicrobial photodynamic therapy in the management of chronic periodontitis.

    Science.gov (United States)

    Betsy, Joseph; Prasanth, Chandra Sekhar; Baiju, Kamalasanan Vijayakumari; Presanthila, Janam; Subhash, Narayanan

    2016-06-01

    The aim of this study is to evaluate patients' perception of antimicrobial photodynamic therapy (aPDT) in the management of chronic periodontitis. 90 patients (51 females and 39 males) with untreated localized chronic periodontitis were randomly assigned to receive SRP with aPDT (test group) or SRP alone (control group) in a single-centered double-blinded randomized and controlled clinical trial. Patients' perception in terms of changes in bleeding gums, pain in gums while chewing, bad breath and sensitive gums along with pain during the procedure and patient acceptance were recorded for 6 months after treatment by a periodontist who was blinded to the procedure. Inter-group and intra-group statistical analyses were performed. Significant difference between the frequencies of two groups with respect to each variable was assessed using non-parametric test. Patients' report of bleeding gums and pain in the gums while chewing showed statistically significant reduction in the test group at 2 weeks and 1 month (phalitosis (phalitosis and pain while chewing following treatment. Further studies are required to assess the effectiveness of aPDT for a longer-term and following multiple sessions. PMID:26805006

  2. Methylene blue photodynamic therapy in rats' wound healing: 21 days follow-up

    Science.gov (United States)

    Carneiro, Vanda Sanderana Macêdo; Catao, Maria Helena Chaves de Vasconcelos; Menezes, Rebeca Ferraz; Araújo, Natália Costa; Gerbi, Marleny Elizabeth Martinez

    2015-06-01

    The experimental evaluated the photodynamic therapy (PDT) in wound healing. It used 60 male rats, making two circular wounds at each animal. They were treated at 48hs intervals, with methylene blue (MB), low level laser treatment (LLLT) or both, thus resulting in PDT. The wounds were observed 01, 03, 07, 14 and 21 days after and then processed and subjected to HE staining to analyze granulation tissue, necrosis, epithelialization and collagen. After day 1, wounds treated with MB showed necrosis less intense than other groups, and the PDT group showed more intense granulation tissue. At day 3, reepithelialization was absent for half of injuries in the PDT group, and this group was also with lower collagen. However, at day 7, this same group presented reepithelialization more advanced than control group, which did not happen with those treated with MB or LLLT (p = 0.015). The results allow us to conclude that PDT difficulted reepithelization at 7th day and interfered in standard healing. However, when used separately, MB and LLLT interfered significantly compared to the control group, which did not happened to the PDT group. There was no significant difference between the treatment groups in other analysed times.

  3. In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

    2009-05-02

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

  4. Photodynamic therapy of HeLa cell cultures by using LED or laser sources.

    Science.gov (United States)

    Etcheverry, María E; Pasquale, Miguel A; Garavaglia, Mario

    2016-07-01

    The photodynamic therapy (PDT) on HeLa cell cultures was performed utilizing a 637nm LED lamp with 1.06W power and m-tetrahydroxyphenyl chlorin (m-THPC) as photosensitizer and compared to a laser source emitting at 654nm with the same power. Intracellular placement of the photosensitizer and the effect of its concentration (CP), its absorption time (TA) and the illumination time (TI) were evaluated. It was observed that for CP>40μg/ml and TA>24h, m-THPC had toxicity on cells in culture, even in the absence of illumination. For the other tested concentrations, the cells remained viable if not subjected to illumination doses. No effect on cells was observed for CPlaser source. Results demonstrate the feasibility of using a LED lamp as alternative to laser source. Here the main characteristic is not the light coherence but achieving a certain light fluence of the appropriate wavelength on cell cultures. We conclude that the efficacy was achieved satisfactorily and is essential for convenience, accessibility and safety. PMID:27152675

  5. Treatment of cutaneous Kaposi's Sarcoma with tin ethyl etiopurpurin (SnET2) photodynamic therapy

    International Nuclear Information System (INIS)

    Purpose: Kaposi's Sarcoma (KS) lesions in immunocompromised individuals are often physiologically and psychologically distressing. The multifocal nature of these lesions makes local treatments (i.e., surgery, radiation) difficult and time consuming. Further, cosmetic outcomes are generally poor. Photodynamic therapy (PDT) can overcome some of these negative outcomes in a single treatment session and as such may be of benefit to these patients. Methods: SnET2 PDT was performed on 9 pts. with known KS lesions. The total number of lesions treated was 121. All patients were HIV positive. The drug SnET2 was intravenously injected and subsequently activated, 24 hours post-injection, by 665 nm light delivered via fiberoptic from a diode laser light source. The total light dose delivered was 300J/sq. cm at a power density of 50-150mW/sq.cm. Response rates were assessed by serial follow-up and patient subjective satisfaction rates were recorded. Results: Subjectively each patient was satisfied with the cosmetic outcome of treatment. Of 8 evaluable patients with 116 lesions response rates were: (CR 75%; PR 19%; NR 0%; 6% of lesions were of Indeterminate status at follow-up). Follow-up ranged from 1-9 months. Adverse experiences were mild to moderate of which 100% were due to sun exposure and did not require treatment. Conclusions: PDT is a well tolerated procedure that produces excellent subjective and objective responses. The patient is treated in a single session on an outpatient basis

  6. CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

    International Nuclear Information System (INIS)

    The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods. (paper)

  7. Photodynamic therapy efficient using high power LED's to eliminate breast cancer cells

    International Nuclear Information System (INIS)

    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/cm2, 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/cm2, 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)

  8. Photodynamic Therapy:A New Approach to Remove Embryos of the Wistar Rat

    Directory of Open Access Journals (Sweden)

    Mohammad Nabiuni

    2010-01-01

    Full Text Available Background: Photodynamic therapy (PDT is a promising new cancer treatment strategy whichinactivates tumor cells by simultaneoulsy using light and a photosensitizer. The similarity betweentumors and newly implanted embryos is notable. Extrauterine pregnancy (EUP does not have adefinite treatment and previous therapeutic options (medical and surgical have not been effectiveor suitable. Therefore, PDT is suggested as a possible treatment for EUP.Materials and Methods: The photosensitizer, hematoporphyrin, was injected locally into theplacenta of one selected embryo from a pregnant Wistar rat (E15. Then, a laser beam wasilluminated at the same point and 48 hours later, changes in the embryo and placenta wereinvestigated. Furthermore, the integrity of the uterus was examined by macroscopic evaluationand sonographic images.Results: Sections obtained from treated and control groups demonstrated that the embryo andplacenta were damaged in the PDT group, whereas the control ones were intact. Furthermore,macroscopic observations and sonographic images during the second parturition after treatmentshowed that the uterus was intact and fertility was preserved.Conclusion: Successful ablation of the treated embryo with no clear damage to the uterus atteststo the success of this approach. The successful use of hematoporphyrin, as a first generationphotosensitizer, should be further investigated for its possible clinical applications.

  9. Photodynamic therapy using upconversion nanoparticles prepared by laser ablation in liquid

    International Nuclear Information System (INIS)

    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

  10. Water-soluble benzylidene cyclopentanone based photosensitizers for in vitro and in vivo antimicrobial photodynamic therapy.

    Science.gov (United States)

    Fang, Yanyan; Liu, Tianlong; Zou, Qianli; Zhao, Yuxia; Wu, Feipeng

    2016-01-01

    Antimicrobial photodynamic therapy (aPDT) has been proposed to cope with the increasing antibiotic resistance among pathogens. As versatile pharmacophores, benzylidene cyclopentanone based photosensitizers (PSs) have been used in various bioactive materials. However, their reports as aPDT agents are very limited, and relationships between their chemical structures and antibacterial abilities have not been systematically discussed. Here, nine water-soluble benzylidene cyclopentanone PSs modified by polyethylene glycol (PEG), carboxylate anionic or pyridyl cationic agents are studied for aPDT. It is found that the binding/uptake abilities and aPDT effects of these PSs toward bacterial cells vary significantly when adjusting the number and position of their terminal charged groups. Though the comparable (also best) binding/uptake amounts are achieved by both cationic PS P3 and anionic PS Y1, only Y1 exhibits much more excellent aPDT activities than other PSs. Antibacterial mechanisms reveal that, relative to the favorable cell wall-binding of cationic PS P3, the anionic PS Y1 can accumulate more in the spheroplast/protoplast of methicillin-resistant Staphylococcus aureus (MRSA), which ensures its high efficient aPDT abilities both in vitro and in vivo. This study suggests the great clinical application potential of Y1 in inactivation of MRSA. PMID:27323899

  11. Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

    Science.gov (United States)

    Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

    2016-07-01

    The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

  12. Smart hyaluronidase-actived theranostic micelles for dual-modal imaging guided photodynamic therapy.

    Science.gov (United States)

    Li, Wenjun; Zheng, Cuifang; Pan, Zhengyin; Chen, Chi; Hu, Dehong; Gao, Guanhui; Kang, Shendong; Cui, Haodong; Gong, Ping; Cai, Lintao

    2016-09-01

    We here report smart hyaluronidase-actived theranostic nanoparticles based on hyaluronic acid (HA) coupled with chlorin e6 (Ce6) via adipic dihydrazide (ADH) forming HA-ADH-Ce6 conjugates and self-assembling into HACE NPs. The resulting nanoparticles showed stable nano-structure in aqueous condition with uniform size distribution and can be actively disassembled in the presence of hyaluronidase (over-expressed in tumor cells), exhibiting hyaluronidase-responsive "OFF/ON" behavior of fluorescence signal. The HACE NPs were rapidly taken up to human lung cancer cells A549 via CD44 (the HA receptor on the surface of tumor cells) receptor mediated endocytosis. Upon laser irradiation, the HACE NPs realized good near-infrared fluorescence imaging and photoacoustic imaging in the tumor bearing mice, which showed 5-fold higher fluorescence intensity and 3-fold higher photoacoustic (PA) intensity than free Ce6, respectively. In addition, under low dose of laser power, the HACE NPs presented more effective photodynamic therapy to suppression of tumor growth than free Ce6 in vitro and in vivo. Overall, these results suggest that the well-defined HACE NPs is a biocompatible theranostic nanoplatform for in vivo dual-modal tumor imaging and phototherapy simultaneously. PMID:27262027

  13. Photodynamic therapy: development of a treatment and dosimetry system adapted to superficial tumors of the bladder

    Science.gov (United States)

    Lignon, Dominique; Jaboin, Y.; Wolf, D.; Meunier-Reynes, Anne; Guillemin, Francois H.

    1993-06-01

    Superficial tumors of the bladder or in situ carcinoma could be interesting indications of Photodynamic Therapy (PDT), since a total mutilating cystectomy could be avoided. The plurifocality of the lesions requires a treatment of the whole mucose; the quantity of light energy must be homogenous and sufficient to induce a therapeutic effect, still non toxic for normal tissues. We therefore developed a system of treatment and intravesical dosimetry control so that the operator can have precise information on the light repartition in the bladder in real time to enable him to optimize the positioning of the irradiation source. This intravesical device consists of twelve light sensors with optical fiber distributed symmetrically against the walls of the bladder; the emitting source is constituted of a scattering isotropic sphere. The signals emitted by the sensors are converted into tension. The acquisition part of the system values consists of two parts : an analogic part, the values are multiplexed on a same oscilloscope track to see in real time their evolution according to the position of the emitting source. The other part is constituted by the numeric acquisition of values for further analysis. We developed, from a mathematical modelisation of the bladder, a centering program of the diffusor that indicates its position in the bladder, as well as a cartography program where the bladder is re-built by interpolation with the different lighting levels.

  14. Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy--Use of Greenhouses and Artificial Light Sources.

    Science.gov (United States)

    Lerche, Catharina M; Heerfordt, Ida M; Heydenreich, Jakob; Wulf, Hans Christian

    2016-02-29

    Daylight-mediated photodynamic therapy (daylight PDT) is a simple and pain free treatment of actinic keratoses. Weather conditions may not always allow daylight PDT outdoors. We compared the spectrum of five different lamp candidates for indoor "daylight PDT" and investigated their ability to photobleach protoporphyrin IX (PpIX). Furthermore, we measured the amount of PpIX activating daylight available in a glass greenhouse, which can be an alternative when it is uncomfortable for patients to be outdoors. The lamps investigated were: halogen lamps (overhead and slide projector), white light-emitting diode (LED) lamp, red LED panel and lamps used for conventional PDT. Four of the five light sources were able to photobleach PpIX completely. For halogen light and the red LED lamp, 5000 lux could photobleach PpIX whereas 12,000 lux were needed for the white LED lamp. Furthermore, the greenhouse was suitable for daylight PDT since the effect of solar light is lowered only by 25%. In conclusion, we found four of the five light sources and the greenhouse usable for indoor daylight PDT. The greenhouse is beneficial when the weather outside is rainy or windy. Only insignificant ultraviolet B radiation (UVB) radiation passes through the greenhouse glass, so sun protection is not needed.

  15. Transcutaneous photodynamic therapy delays the onset of paralysis in a murine multiple sclerosis model

    Science.gov (United States)

    Hunt, David W. C.; Leong, Simon; Levy, Julia G.; Chan, Agnes H.

    1995-03-01

    Photodynamic therapy (PDT) using benzoporphyrin derivative (BPD, Verteporfin) and whole body irradiation, can affect the course of adoptively transferred experimental allergic (autoimmune) encephalomyelitis (EAE) in PL mice. Murine EAE is a T cell-mediated autoimmune disease which serves as a model for human multiple sclerosis. Using a novel disease induction protocol, we found that mice characteristically developed EAE within 3 weeks of receipt of myelin basic protein (MBP)-sensitized, in vitro-cultured spleen or lymph node cells. However, if animals were treated with PDT (1 mg BPD/kg bodyweight and exposed to whole body 15 Joules cm2 of LED light) 24 hours after receiving these cells, disease onset time was significantly delayed. PDT-treated mice developed disease symptoms 45 +/- 3 days following cell administration whereas untreated controls were affected within 23 +/- 2 days. In contrast, application of PDT 48 or 120 hours following injection of the pathogenic cells had no significant effect upon the development of EAE. Experiments are in progress to account for the protective effect of PDT in this animal model. These studies should provide evidence on the feasibility of PDT as a treatment for human autoimmune disease.

  16. Photodynamic Therapy (PDT with Chemotherapy for Advanced Lung Cancer with Airway Stenosis

    Directory of Open Access Journals (Sweden)

    Masakazu Kimura

    2015-10-01

    Full Text Available Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi bronchial stenosis and obstruction. We present data for 12 (eight men, four women consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58–80 years, and the stages of cancer were IIA–IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%–100%, 15% (range, 15%–99%, and 15% (range 15%–60%, respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction.

  17. Multifunctional Peptide-Conjugated Hybrid Silica Nanoparticles for Photodynamic Therapy and MRI

    Directory of Open Access Journals (Sweden)

    Hamanou Benachour, Aymeric Sève, Thierry Bastogne, Céline Frochot, Régis Vanderesse, Jordane Jasniewski, Imen Miladi, Claire Billotey, Olivier Tillement, François Lux, Muriel Barberi-Heyob

    2012-01-01

    Full Text Available Photodynamic therapy (PDT is an emerging theranostic modality for various cancer as well as non-cancer diseases. Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue. The vascular effect is widely accepted to play a major role in tumor eradication by PDT. To promote this vascular effect, we previously demonstrated the interest of using an active- targeting strategy targeting neuropilin-1 (NRP-1, mainly over-expressed by tumor angiogenic vessels. For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer. The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting. In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose. Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein. Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue. Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

  18. Transurethral photodynamic therapy in benign prostatic hyperplasia : a canine pilot study using benzoporphyrin derivative

    Science.gov (United States)

    Shetty, Sugandh D.; Peabody, James O.; Beck, Elsa R.; Cerny, Joseph C.; Amin, Mahul B.; Richter, Anna M.

    1999-06-01

    Photodynamic therapy (PDT) principles were evaluated in management of benign prostatic hyperplasia (BPH) in a canine model. Five dogs were injected with benzoporphyrin derivative (BPD) and samples of prostate, bladder, urethra and rectum were taken at 1, 2, 3 and 4 hours and analyzed for BPD. Next, 16 dogs were treated with 100 Joules at 690 nm light form argon dye laser 1 hour after administration of BPD at 0.5 mg/kg using cylindrical diffuser tip fiber passed transurethrally. The prostates were harvested weekly up to 4 weeks and the size of the lesion was measured and the prostates were examined. Prostate had the highest BPD levels. Hemorrhagic lesion of 2.5 cm in diameter was noted at 1 week after PDT. At 3 and 4 weeks there were changes of glandular atrophy in the periurethral region. Minimally invasive technique of transurethral PDT causes glandular and stromal changes in the periurethral zone and has potential in the treatment of BPH.

  19. 5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

    Directory of Open Access Journals (Sweden)

    Lin Yu-Hsin

    2010-04-01

    Full Text Available Abstract Photodynamic therapy (PDT has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK and mitogen-activated protein kinase (MAPK signaling cascades are activated following 5-aminolevulinic acid (ALA-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy.

  20. Photodynamic therapy for early malignancies in the lower female genital tract

    Science.gov (United States)

    Lobraico, Rocco V.

    1990-09-01

    A total of 14 patients who had failed all conventional modalities for cancer of the vulva vagina and perianal area were treated with photodynamic therapy PDT. The affinity of porphyrins to neopJ. astic tissue enables treatment to be concentrated at the tumor site. An Aurora FL Argon pumped dye laser (Cooper LaserSonics Inc. USA) was used to pump dicyanomethylene dye as an activating source for a red light at a wavelength of 630 nm. The combination of a tumor localizing photosensitizer and photoactivating red light produces a photo chemical reaction that is destructive to the cancerous lesion. The treatment time varied between 10-30 minutes. Vulvar sites ranged from 9-38 cm2. Delivered light doses were from 50-125 J/cm2 and power density from 50 to 75 mW/cm2. A complete response was obtained in 80 of the sites treated as evidenced by negative biopsies taken at 3 months post treatment. Adverse reactions to PDT included a transient cutaneous photosensitivity due to retention of the photosensitizers in the skin. This reaction usually persisted from 45-60 days. 1.

  1. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis.

    Science.gov (United States)

    Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi

    2015-10-23

    Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58-80 years), and the stages of cancer were IIA-IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%-100%), 15% (range, 15%-99%), and 15% (range 15%-60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction.

  2. The photodynamic therapy on Streptococcus mutans biofilms using erythrosine and dental halogen curing unit.

    Science.gov (United States)

    Lee, Young-Ho; Park, Ho-Won; Lee, Ju-Hyun; Seo, Hyun-Woo; Lee, Si-Young

    2012-12-01

    The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain-heart infusion (BHI) broth supplemented with 0% or 0.1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose.

  3. Delmopinol-induced matrix removal facilitates photodynamic therapy and chlorhexidine methods for disinfecting mixed oral biofilms

    Science.gov (United States)

    Rogers, Stephen Christopher

    It is often observed that the slimy matrixes of various bacterial-formed biofilms can limit their disinfection. This investigation demonstrated that disinfection effectiveness by either photodynamic therapy (PDT) or chlorhexidine irrigation is significantly improved by collapse of that matrix using the non-bactericidal reagent delmopinol as part of the treatment sequence. Cyclic shear-producing conditions were used to grow 4-day, whole salivary and growth media biofilms on glow-discharge-treated polystyrene (N=46) and mini-germanium internal reflection prisms to serve in a periodontal crypt model of disinfection by either methylene-blue-mediated PDT or by chlorhexidine irrigation. Assays for bacterial viability, with and without treatments, were performed by alamarBlueRTM fluorescent methods, statistically applied (ANOVA, Tukey's HSD). Multiple Attenuated Internal Reflection Infrared (MAIR-IR) assays confirmed selective removal of the predominantly polysaccharide matrix materials by the delmopinol treatment, but not by equivalent water or chlorhexidine methods. Confocal-IR microscopy showed that the delmopinol reagent, alone, caused about one-third of each wet biofilm to be removed, while bacterial re-growth was confirmed by alamarBlueRTM assay. Chlorhexidine and PDT suppression of bacterial activity without regrowth was significantly improved with the added delmopinol treatment, and is likely to provide similarly beneficial results in the effective disinfection of diverse biofilms in many settings.

  4. 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 oral streptococci in vitro.

  5. Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells.

    Science.gov (United States)

    Lim, Eun Jin; Oak, Chul-Ho; Heo, Jeonghoon; Kim, Young-Ho

    2013-08-01

    Combined treatment with a photosensitizer and iodide laser [photodynamic therapy (PDT)] has improved the outcome of various cancers. In this study, we investigated the effects of using the photosensitizer methylene blue (MB) in PDT in human lung adenocarcinoma cells. We found that MB enhances PDT-induced apoptosis in association with downregulation of anti-apoptotic proteins, reduced mitochondrial membrane potential (MMP), increased phosphorylation of the mitogen-activated protein kinase (MAPK) and the generation of reactive oxygen species (ROS). In MB-PDT-treated A549 cells, we observed PARP cleavage, procaspase-3 activation, downregulation of the anti-apoptotic proteins Bcl-2 and Mcl-1, and the reduction of mitochondrial membrane potential (MMP). Western blot data showed that phosphorylation of p38 was increased in MB-PDT-treated A549 cells, indicating that several signaling molecules participate in the apoptotic cascade. Our data also showed that apoptotic cell death in MB-PDT-treated cells occurred through a series of steps beginning with the photochemical generation of ROS. Demonstrating the role of ROS, pretreatment of A549 cells with the antioxidant N-acetylcysteine (NAC) followed by MB-PDT resulted in increased cell viability and reduced proteolytic cleavage of PARP.

  6. Enhanced photodynamic therapy efficacy of methylene blue-loaded calcium phosphate nanoparticles.

    Science.gov (United States)

    Seong, Da-Young; Kim, Young-Jin

    2015-05-01

    Although methylene blue (MB) is the most inexpensive photosensitizer with promising applications in the photodynamic therapy (PDT) for its high quantum yield of singlet oxygen generation, the clinical use of MB has been limited by its rapid enzymatic reduction in the biological environment. To enhance PDT efficacy of MB by preventing the enzymatic reduction, we have developed a new mineralization method to produce highly biocompatible MB-loaded calcium phosphate (CaP-MB) nanoparticles in the presence of polymer templates. The resulting CaP-MB nanoparticles exhibited spherical shape with a size of under 50 nm. Fourier transform infrared (FT-IR) and zeta-potential analyses confirmed the insertion of MB into the CaP-MB nanoparticles. The encapsulation of MB in CaP nanoparticles could effectively protect MB from the enzymatic reduction. In addition, the CaP-MB nanoparticles exhibited a good biocompatibility in the dark condition and significantly enhanced PDT efficacy due to apoptotic cell death against human breast cancer cells as compared with free MB, implying that CaP-MB nanoparticle system might be potentially applicable in PDT.

  7. Photodynamic therapy can induce a protective innate immune response against murine bacterial arthritis via neutrophil accumulation.

    Directory of Open Access Journals (Sweden)

    Masamitsu Tanaka

    Full Text Available BACKGROUND: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT and preventive (Pre-PDT effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.

  8. Dosimetry study of PHOTOFRIN-mediated photodynamic therapy in a mouse tumor model

    Science.gov (United States)

    Qiu, Haixia; Kim, Michele M.; Penjweini, Rozhin; Zhu, Timothy C.

    2016-03-01

    It is well known in photodynamic therapy (PDT) that there is a large variability between PDT light dose and therapeutic outcomes. An explicit dosimetry model using apparent reacted 1O2 concentration [1O2]rx has been developed as a PDT dosimetric quantity to improve the accuracy of the predicted ability of therapeutic efficacy. In this study, this explicit macroscopic singlet oxygen model was adopted to establish the correlation between calculated reacted [1O2]rx and the tumor growth using Photofrin-mediated PDT in a mouse tumor model. Mice with radiation-induced fibrosarcoma (RIF) tumors were injected with Photofrin at a dose of 5 mg/kg. PDT was performed 24h later with different fluence rates (50, 75 and 150 mW/cm2) and different fluences (50 and 135 J/cm2) using a collimated light applicator coupled to a 630nm laser. The tumor volume was monitored daily after PDT and correlated with the total light fluence and [1O2]rx. Photophysical parameters as well as the singlet oxygen threshold dose for this sensitizer and the RIF tumor model were determined previously. The result showed that tumor growth rate varied greatly with light fluence for different fluence rates while [1O2]rx had a good correlation with the PDT-induced tumor growth rate. This preliminary study indicated that [1O2]rx could serve as a better dosimetric predictor for predicting PDT outcome than PDT light dose.

  9. Photodynamic Therapy for Upper Gastrointestinal Cancers during Past 25 Years in China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To evaluate the status of photodynamic therapy (PDT) for upper gastrointestinal cancers, and then discuss how to solve the problems that hinder the development of PDT. Methods: A total of 30 pertinent literatures about PDT for upper gastrointestinal cancers during past 25 years were collected through the retrieval of several related medical databases (Chinese Medical Current Contents, China Bio-Medical Bibliographic Database, China Journal Fulltext Database). The data, including the gender, age of patients, tumor position, pathologic findings, treatment efficacy, adverse effects and the applied laser and photosensitizer, were statistically analyzed.Results: For all the 1687 cases with upper gastrointestinal cancers, the excellent-effective rate (complete remission or prominent remission) and effective rate (complete remission or prominent remission or minor remission) were 53.2% and 87%, respectively. The therapeutic effect of combined treatment(PDT with other methods) was superior to that of PDT (u=4.456, P<0.01). All the involved pathological types were sensitive to PDT. Different photosensitizers and lasers were used by different authors, but all of them were effective without any serious side effect. Conclusion: PDT shows a radical effect on the tumors of early stage and a favorable palliative effect on the tumors of advanced stage, so it is one of the optional strategies for the treatment of upper gastrointestinal cancers.

  10. Lifetime-resolved photoacoustic (LPA) spectroscopy for monitoring oxygen change and photodynamic therapy (PDT)

    Science.gov (United States)

    Jo, Janggun; Lee, Chang Heon; Kopelman, Raoul; Wang, Xueding

    2016-03-01

    The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.

  11. 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.

  12. Photodynamic therapy-induced programmed cell death in carcinoma cell lines

    Science.gov (United States)

    He, Xiao-Yan; Sikes, Robert A.; Thomsen, Sharon L.; Chung, L.; Jacques, Steven L.

    1993-06-01

    The mode of cell death following photodynamic therapy (PDT) was investigated from the perspective of programmed cell death (apoptosis). Human prostate carcinoma cells (PC3), human non-small cell lung carcinoma (H322a), and rat mammary carcinoma (MTF7) were treated by PDT following sensitization with dihematoporphyrin ether (DHE). The response of these carcinoma cell lines to PDT was variable. An examination of extracted cellular DNA by gel electrophoresis showed the characteristic DNA ladder pattern indicative of internucleosomal cleavage of DNA during apoptosis. MTF7 and PC3 responded to PDT by inducing apoptosis while H322a had no apoptotic response. The magnitude of the response and the PDT dosage required to induce the effect were different in PC3 and MTF7. MTF7 cells responded with rapid apoptosis at the dose of light and drug that yielded 50% cell death (LD50). In contrast, PC3 showed only marginal apoptosis at the LD50 but had a marked response at the LD85. Furthermore, the onset of apoptosis followed slower kinetics in PC3 (2 hr - 4 hr) than in MTF7 (cells were killed by PDT but failed to exhibit any apoptotic response. This study indicates that apoptosis may occur during PDT induced cell death, but this pathway is not universal for all cancer cell lines.

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

    Science.gov (United States)

    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 (pcandidiasis. PMID:27253525

  14. Photodynamic therapy in the cattle protozoan Tritrichomonas foetus cultivated on superhydrophilic carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    Machado, Susane Moreira [Laboratory of Tissue and Cell Biology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Pacheco-Soares, Cristina [Laboratory of Tissue and Cell Biology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Laboratory of Dynamics of Cellular Compartments, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Marciano, Fernanda Roberta; Lobo, Anderson Oliveira [Laboratory of Biomedical Nanotechnology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Soares da Silva, Newton, E-mail: nsoares@univap.br [Laboratory of Tissue and Cell Biology, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil); Laboratory of Dynamics of Cellular Compartments, Development and Research Institute (IP and D), Universidade do Vale do Paraíba (UNIVAP), Av. Shishima Hifumi 2911, Urbanova, 12244-000 São José dos Campos, SP (Brazil)

    2014-03-01

    Superhydrophilic vertically aligned carbon nanotubes (VACNT-O{sub 2}) were used for the first time as scaffolds for photodynamic therapy (PDT) to induce inhibition of cell division in eukaryotic cells. VACNT-O{sub 2} scaffolds were produced on Ti substrates using plasma enhanced chemical vapor deposition technique and functionalized by oxygen plasma. Scanning electron microscopy (SEM) analysis was performed to characterize the surface changes of the protozoan and interaction with VACNT-O{sub 2}. Characterization of lipid and total protein expression was performed with protozoa that were or not treated with PDT. Quantification of protein was conducted using Qubit fluorometer and separated on a polyacrylamide gel. SEM analysis showed the release of lipid vesicles by protozoa after the PDT. These vesicles were characterized by the PKH26 fluorescent probe. The results demonstrated a greater amount of protein released after PDT than in the control. When analyzing the protein material in polyacrylamide gel, a significant protein expression of approximately 65 kDa was found. A model identified the programmed death of Tritrichomonas foetus after the PDT was also proposed. - Highlights: • VAMWCNT-O{sub 2} used for the first time as scaffolds for study in parasitic protozoan. • VAMWCNT-O{sub 2} films applied to understand spreading mechanisms of parasitic protozoan. • A release of a protein of approximately 65kDa of protozoan was also observed.

  15. 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.

  16. 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.

  17. Metal Oxide Nanomaterials in Nanomedicine: Applications in Photodynamic Therapy and Potential Toxicity.

    Science.gov (United States)

    He, Xiaojia; Aker, Winfred G; Huang, Ming-Ju; Watts, John D; Hwang, Huey-Min

    2015-01-01

    Metal oxide nanomaterials have exhibited excellent performance as nanomedicines in photodynamic therapy (PDT) for cancer and infection treatment. Their unique and tunable physicochemical properties advance them as promising alternatives in drug delivery, early diagnosis, imaging, and treatment against various tumors and infectious diseases. Moreover, the implementation of nanophototherapy in deep tissue sites is enhanced by advancements in photosensitization technology. Notwithstanding the progress made in emerging metal oxide nanomaterials-derived PDT, the potential toxicity towards adjunct tissues associated with this approach remains challenging. Regulation and legislation have also been recommended and subsequently enacted in response to public concerns related to large-scale production, transportation, use, and disposal of those nanomaterials. Consequently, a quantitative structure-activity relationship (QSAR) paradigm has been adopted and is widely used in evaluating and predicting the side effects of nanomedicines, thus influencing their design and fabrication. This article briefly reviews the application of metal oxide nanomaterials in PDT and their associated adverse impacts as reported in recent publications. The future trends and implications of this platform in nanomedicine are also highlighted. However, more studies and efforts have to be carried out for developing novel nano-therapeutics with high selectivity, sensitivity, biocompatibility, and minimal side effects in PDT.

  18. Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

    Science.gov (United States)

    Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2016-01-01

    This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

  19. Usefulness of a wavelength tunable optical parametric oscillator laser on photodynamic therapy

    Science.gov (United States)

    Nishiwaki, Yoshiro; Yoshida, Takato O.; Nakamura, Satoshi; Baba, Shozo; Matsusawa, Eiji; Suzuki, Hideo; Hirano, Toru

    1995-03-01

    By rotating the optical axis of a nonlinear optical crystal ((beta) -BaB2O4), a tunable laser beam could be obtained from an optical parametric oscillator (OPO) laser. When the crystal was optically pumped by the third harmonics of the 1064 nm Nd:YAG laser, we had a coherent beam from 410 nm through 2550 nm continuously without changing the optical cavity. We compared photodynamic therapy (PDT) effects of two photosensitizers, phenophorbide a(Phd) and Photosan-3(Ph-3, hematoporphyrin-polyester), on Wistar rat liver. Twenty-four hours after sensitization (5 mg/kg i.v.), 670 nm and 630 nm light (75 mW/cm2) was irradiated for Phd and Ph-3 respectively at energy doses of 25, 50, and 100 J/cm2. The rats were sacrificed 24 hours after laser irradiation and analyzed pathologically. Phd produced more severe necrosis than Ph-3. Twenty-five J/cm2 of Phd was identical with 100 J/cm2 of Ph-3. Next, we treated HeLa cell tumors of nude mice by Phd 670 nm PDT and Ph-3 630 nm PDT. The PDT effects of the two photosensitizers on HeLa cell tumors were similar to those on normal liver tissue. In conclusion the OPO laser could make it possible to compare PDT effects of photosensitizers by activating them with their matched wavelengths.

  20. New optional photodynamic therapy laser wavelength for infantile port wine stains: 457 nm

    Science.gov (United States)

    Wang, Ying; Zuo, Zhaohui; Gu, Ying; Huang, Naiyan; Chen, Rong; Li, Buhong; Qiu, Haixia; Zeng, Jing; Zhu, Jianguo; Liang, Jie

    2012-06-01

    To expand the optional laser wavelengths of photodynamic therapy (PDT) for port wine stain (PWS), the feasibility of applying a 457 nm laser to the PDT for infantile PWS was analyzed by mathematical simulation and was validated by clinical experiment. Singlet oxygen yield of 457 nm PDT or 532 nm PDT in an infantile PWS model and an adult PWS model was theoretically simulated. Fifteen PWS patients (14 infants and 1 adult) with 40 spots were treated with 457 nm (20 spots) and 532 nm (20 spots), respectively, in two PDT courses. Simulation results showed that under the same power density and irradiation time, singlet oxygen yield of 457 nm PDT and 532 nm PDT are similar in infantile PWS vessels. Yet, in adult PWS vessels, singlet oxygen yield of 457 nm PDT is lower than 532 nm PDT. Clinical outcomes showed that no statistic difference existed between 457 nm PDT and 532 nm PDT for infantile PWS. The result of this study suggested that 457 nm wavelength laser has the potential to be applied in PDT for infantile PWS.

  1. The evaluation and planning of light dose in photodynamic therapy for port wine stains

    Science.gov (United States)

    Zhang, Feng-juan; Hu, Xiaoming; Zhang, Qi-shen

    2014-11-01

    Photodynamic therapy (PDT) is one of the best available treatment for dermatology, especially for port wine stains (PWS), in which the efficacy is associated with the light dose, the photosensitizer concentration, the oxygen concentration and so on. Accurate control of the light dose will help doctors develop more effective treatment protocols, and reduce the treatment cost. Considering the characters of PWS, a binocular vision system composed of a camera, a digital projector and a computing unit is designed. An accurate 3D modeling of patients was achieved using a gray coding structured light, and then the lesions were segmented based on HSV space. Subsequently, each 3D point is fit on the surface by a nearest neighbor algorithm and the surface normal can be obtained. Three dimensional localization of lesion provide digital objective basis for automatic control of light device. The irradiance on the surface at a given angle can be assessed, and the optimum angle for the treatment can be solved and optimized by the doctor to improve irradiation areas.

  2. Choosing optimal wavelength for photodynamic therapy of port wine stains by mathematic simulation

    Science.gov (United States)

    Wang, Ying; Gu, Ying; Zuo, Zhaohui; Huang, Naiyan

    2011-09-01

    Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine stains (PWS). However, how these wavelengths result in different PDT outcomes has not been clearly illuminated. This study is designed to analyze which wavelengths would be the most advantageous for use in PDT for PWS. The singlet oxygen yield in PDT-treated PWS skin under different wavelengths at the same photosensitizer dosage was simulated and the following three situations were simulated and compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation at clinical dosage (100 mW/cm2, 40 min); 2. PDT efficiency of different wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency of different wavelengths for PWS, in which only deeply located ectatic vessels remained. The results showed that singlet oxygen yield is the highest at 510 nm, it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This result is identical to the state in clinic. According to this theoretical study, the optimal wavelength for PDT in the treatment of PWS should near the absorption peaks of photosensitizer and where absorption from native chromophores (haemoglobin and melanin) is diminished.

  3. Titania coated upconversion nanoparticles for near-infrared light triggered photodynamic therapy.

    Science.gov (United States)

    Lucky, Sasidharan Swarnalatha; Muhammad Idris, Niagara; Li, Zhengquan; Huang, Kai; Soo, Khee Chee; Zhang, Yong

    2015-01-27

    Because of the limited penetration depth of visible light that generally excites most of the available photosensitizers (PSs), conventional photodynamic therapy (PDT) is limited to the treatment of superficial and flat lesions. Recently, the application of deep penetrating near-infrared (NIR) light excitable upconversion nanoparticles (UCNs) in conjunction with PDT has shown to have clear potential in the treatment of solid tumors due to its ability to penetrate thick tissue. However, various constructs developed so far have certain limitations such as poor or unstable PS loading, reducing their therapeutic efficacy and limiting their application to solution or cell-based studies. In this work, we present a method to fabricate uniform core-shell structured nanoconstruct with a thin layer of photocatalyst or PS-titanium dioxide (TiO2) stably coated on individual UCN core. Our design allows controllable and highly reproducible PS loading, preventing any leakage of PS compared to previously developed nanoconstructs, thus ensuring repeatable PDT results. Further surface modification of the developed nanoconstructs with polyethylene glycol (PEG) rendered them biocompatible, demonstrating good therapeutic efficacy both in vitro and in vivo.

  4. Photodynamic therapy affects the expression of IL-6 and IL-10 in vivo

    Science.gov (United States)

    Gollnick, Sandra O.; Musser, David A.; Henderson, Barbara W.

    1998-05-01

    Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response which potentiates anti-tumor immunity, but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood, but are likely to involve meditation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10. IL-6 mRNA and protein are rapidly and strongly enhanced in the PDT treated EMT6 tumor. Previous studies have shown that intratumoral injection of IL- 6 or transduction of the IL-6 gene into tumor cells can enhance tumor immunogenicity and inhibit tumor growth in experimental murine tumor systems. Thus, PDT may enhance local anti-tumor immunity by up-regulating IL-6. PDT also results in an increase in IL-10 mRNA and protein in the skin. The same PDT regime which enhances IL-10 production in the skin has been shown to strongly inhibit the CHS response. The kinetics of IL-10 expression coincide with the known kinetics of PDT induced CHS suppression and we propose that the enhanced IL-10 expression plays a role in the observed suppression of cell mediated responses seen following PDT.

  5. 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

    2016-01-01

    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. PMID:27213356

  6. Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

    Science.gov (United States)

    Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

    2015-05-01

    There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

  7. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence.

    Science.gov (United States)

    Zhang, Chen; Zhao, Kuaile; Bu, Wenbo; Ni, Dalong; Liu, Yanyan; Feng, Jingwei; Shi, Jianlin

    2015-02-01

    Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing-radiation-induced PDT agent, achieving synchronous radiotherapy and depth-insensitive PDT with diminished oxygen dependence. In the core-shell Ce(III)-doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the Ce(III)-doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron-hole (e(-)-h(+)) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy.

  8. Photodynamic therapy induces epidermal thickening in hairless mice skin: an optical coherence tomography assessment

    Science.gov (United States)

    Jorge, Ana Elisa S.; Campos, Carolina P.; Freitas, Anderson Z.; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) promotes skin improvement according to many practitioners, however the immediately in vivo assessment of its response remains clinically inaccessible. As a non-invasive modality, optical coherence tomography (OCT) has been shown a feasible optical diagnostic technique that provides images in real time, avoiding tissue biopsies. For this reason, our investigation focused on evaluates the PDT effect on a rodent model by means of OCT. Therefore, a normal hairless mouse skin has undergone a single-session PDT, which was performed with topical 5- aminolevulinic acid (ALA) cream using a red (630 nm) light emitting diode (LED) which reached the light dose of 75 J/cm2. As the optical imaging tool, an OCT (930 nm) with axial resolution of 6.0 microns in air was used, generating images with contact to the mouse skin before, immediately after, 24 hours, and 2 weeks after the correspondent procedure. Our result demonstrates that, within 24 hours after ALA-PDT, the mouse skin from the PDT group has shown epidermal thickness (ET), which has substantially increased after 2 weeks from the treatment day. Moreover, the skin surface has become evener after ALA-PDT. Concluding, this investigation demonstrates that the OCT is a feasible and reliable technique that allows real-time cross-sectional imaging of skin, which can quantify an outcome and predict whether the PDT reaches its goal.

  9. 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.

  10. 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/cm2), 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 SMIC

  11. Effective Combination of Photodynamic Therapy and Imiquimod 5% Cream in the Treatment of Actinic Keratoses: Three Cases

    Directory of Open Access Journals (Sweden)

    Laura Held

    2013-01-01

    Full Text Available Background. The therapy for actinic keratoses includes photodynamic therapy (PDT and imiquimod 5% cream. The sequential use of both could result in better clinical outcomes. Objectives. To enhance efficacy of therapies while improving tolerability, convenience, and patient adherence with a scheme combining two concomitant or sequential AK treatments. Methods. All patients underwent one session of conventional PDT. Two weeks after, the PDT imiquimod 5% cream was applied to the treatment area once daily for three days per week. One course continued for four weeks followed by a clinical evaluation and decision about further treatment. Patients who had not cleared all of their AK lesions in the treatment area in course 1 participated in a second 4-week course of treatment. Limitations. Small size of population. Results. Three participants were enrolled. Two patients showed complete clinical clearance of AKs. The effect was also noted after long-term followup, at months seven and eleven. No subject discontinued for an adverse event. There were severe local skin reactions in two participants which were severe erythema, scaling, and crusting. One patient showed no response to the therapy. Conclusions. Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses. This initial proof-of-concept should be studied in larger clinical trials.

  12. 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

  13. A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy

    Science.gov (United States)

    Wei, Yanchun; Zhou, Feifan; Zhang, Da; Chen, Qun; Xing, Da

    2016-02-01

    Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in

  14. Confocal Fluorescence Imaging Enables Noninvasive Quantitative Assessment of Host Cell Populations In Vivo Following Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Soumya Mitra, Oleg Mironov, Thomas H. Foster

    2012-01-01

    Full Text Available We report the use of optical imaging strategies to noninvasively examine photosensitizer distribution and physiological and host responses to 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH-mediated photodynamic therapy (PDT of EMT6 tumors established in the ears of BALB/c mice. 24 h following intravenous (IV administration of 1 μmol kg-1 HPPH, wide-field fluorescence imaging reveals tumor selectivity with an approximately 2-3-fold differential between tumor and adjacent normal tissue. Confocal microscopy demonstrates a relatively homogeneous intratumor HPPH distribution. Labeling of host cells using fluorophore-conjugated antibodies allowed the visualization of Gr1+/CD11b+ leukocytes and major histocompatibility complex class II (MHC-II+ cells in vivo. Imaging of the treated site at different time-points following irradiation shows significant and rapid increases in Gr1+ cells in response to therapy. The maximum accumulation of Gr1+ cells is found at 24 h post-irradiation, followed by a decrease at the 48 h time-point. Using IV-injected FITC-conjugated dextran as a fluorescent perfusion marker, we imaged tissue perfusion at different times post-irradiation and found that the reduced Gr1+ cell density at 48 h correlated strongly with functional damage to the vasculature as reported via decreased perfusion status. Dual color confocal imaging experiments demonstrates that about 90% of the anti-Gr1 cell population co-localized with anti-CD11b labeling, thus indicating that majority of the Gr1-labeled cells were neutrophils. At 24 h post-PDT, an approximately 2-fold increase in MHC-II+ cells relative to untreated control is also observed. Co-localization analysis reveals an increase in the fraction of Gr1+ cells expressing MHC-II, suggesting that HPPH-PDT is stimulating neutrophils to express an antigen-presenting phenotype.

  15. Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis.

    Science.gov (United States)

    Gualberto, Erivan Clementino; Theodoro, Letícia Helena; Longo, Mariellén; Novaes, Vivian Cristina Noronha; Nagata, Maria José Hitomi; Ervolino, Edilson; Garcia, Valdir Gouveia

    2016-01-01

    The aim of this study was to compare the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of experimentally induced periodontitis in female rats that were systemically treated with or without nicotine. Female rats (n = 180) were divided into two groups: vehicle administration (Veh) and nicotine administration (Nic). Mini-pumps containing either vehicle or nicotine were implanted in the rats 30 days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7 days, the ligature was removed, and the rats were randomly divided into three treatment subgroups: SRP (only SRP), DL (SRP plus diode laser), and aPDT (SRP plus aPDT). The aPDT consisted of phenothiazine photosensitizer deposition followed by diode laser irradiation. Ten rats from each subgroup were euthanized at 7, 15, and 30 days after treatment. Alveolar bone loss (ABL) in the furcation region was evaluated using histological, histometric, and immunohistochemical analyses. The rats that were treated with nicotine showed more ABL compared to those treated with vehicle. In both the Veh and Nic groups, SRP plus aPDT treatment resulted in reduced ABL, smaller numbers of both TRAP- and RANKL-positive cells, and higher numbers of PCNA-positive cells compared to SRP treatment alone. aPDT was an effective adjunctive therapy for the treatment of periodontitis in female rats regardless of whether they received nicotine.

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

    Directory of Open Access Journals (Sweden)

    José Chibebe Junior

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

  17. ALA-mediated photodynamic therapy of experimental malignant glioma in the BD-IX rat model

    Science.gov (United States)

    Hirschberg, Henry; Angell-Petersen, Even; Peng, Qian; Sun, Chung-Ho; Sorensen, Dag R.; Carper, Steven W.; Madsen, Steen J.

    2005-04-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resec-tion indicating that a more aggressive form of local therapy could be of benefit. Photodynamic therapy (PDT) is a local form of treatment involving the administration of a tumor-localizing photosensitizing drug that is activated by light of a specific wavelength The results of in vitro experiments indicated that PDT, given at low fluence rates was substantially more effective at inhibiting glioma spheroid growth than short term high fluence rate regimes. This prompted the initia-tion of in vivo studies of low fluence rate 5-aminolevulinic acid (ALA) PDT in a rat glioma model. Methods:BT4C cell line tumors were established in the brains of inbred BD- IX rats. Eighteen days following tumor induction the animals were injected with 125 mg/kg ALA ip. and four hours later light treatment at various fluences and fluence rates were given after the introduction of an optical fiber. Tumor histology and animal survival were examined. Results: In vitro experiments verified that the cell line was sensitive to ALA PDT. Microfluorometry of frozen tissue sections showed that PpIX is produced with a greater than 20:1 tumor to normal tissue selectivity ratio four hours after ALA injection. Histological examination demonstrated neutrophil infiltration and tumor central necrosis in low fluence rate treated tumors. Conclusions: Low fluence rate long term ALA mediated PDT had a more pronounced effect on tumor histology than single shot short duration treatments at similar total fluence levels.

  18. Monte Carlo fluence simulation for prospective evaluation of interstitial photodynamic therapy treatment plans

    Science.gov (United States)

    Cassidy, Jeffrey; Betz, Vaughn; Lilge, Lothar

    2015-03-01

    Photodynamic therapy (PDT) delivers a localized cytotoxic dose that is a function of tissue oxygen availability, photosensitive drug concentration, and light fluence. Providing safe and effective PDT requires an understanding of all three elements and the physiological response to the radicals generated. Interstitial PDT (IPDT) for solid tumours poses particular challenges due to complex organ geometries and the associated limitations for diffusion theory based fluence rate prediction, in addition to restricted access for light delivery and dose monitoring. As a first step towards enabling a complete prospective IPDT treatment-planning platform, we demonstrate use of our previously developed FullMonte tetrahedral Monte Carlo simulation engine for modeling of the interstitial fluence field due to intravesicular insertion of brief light sources. The goal is to enable a complete treatment planning and monitoring work flow analogous to that used in ionizing radiation therapy, including plan evaluation through dose-volume histograms and algorithmic treatment plan optimization. FullMonte is to our knowledge the fastest open-source tetrahedral MC light propagation software. Using custom hardware acceleration, we achieve 4x faster computing with 67x better power efficiency for limited-size meshes compared to the software. Ongoing work will improve the performance advantage to 16x with unlimited mesh size, enabling algorithmic plan optimization in reasonable time. Using FullMonte, we demonstrate significant new plan-evaluation capabilities including fluence field visualization, generation of organ dose-volume histograms, and rendering of isofluence surfaces for a representative bladder cancer mesh from a real patient. We also discuss the advantages of MC simulations for dose-volume histogram generation and the need for online personalized fluence-rate monitoring.

  19. 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. PMID:7739367

  20. Influence of different output powers on the efficacy of photodynamic therapy with 809-nm diode laser and indocyanine green

    Science.gov (United States)

    Topaloglu, Nermin; Yuksel, Sahru; Gulsoy, Murat

    2013-02-01

    Photodynamic therapy (PDT) is an alternative antimicrobial treatment method. Different wavelengths of light sources mostly in the visible spectrum have been investigated for antimicrobial Photodynamic Therapy. Even though the wavelengths in near infrared spectrum have the advantage of higher penetration capability in biological tissue, they have not been preferred for PDT because of their possible photothermal effect in biological tissues. In our previous studies, the desired PDT effect was achieved with 809-nm diode laser and indocyanine green (ICG) on drug resistant pathogens. In this study, it was aimed to investigate the influence of different output powers during PDT applications with 809-nm diode laser to clarify whether there is a photothermal effect to kill the pathogens or only the photochemical effect of photodynamic therapy. 4 different output powers (500 mW, 745 mW, 1000 mW, 1500 mW) were examined in Laseronly and PDT groups of P. aeruginosa ATCC 27853 in vitro. In the PDT groups, a non-phototoxic ICG concentration (50 μl/ml) has been chosen to eliminate the toxic effect of ICG and evaluate only the thermal effect of laser. Applied energy dose (252 J/cm2) was kept constant by increasing the exposure duration (300, 240, 180 and 120 seconds respectively). These output powers in Laser-only or PDT groups did not seem to cause photothermal effect. There was not any significant decrease or increase on bacterial load after the applications with different output powers. Higher output powers in PDT groups with the same ICG concentration did not cause any higher killing effect.