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Sample records for 5-ala mediated photodynamic

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

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    Atif, M.; Fakhar-e-Alam, M.; Firdous, S.; Zaidi, S. S. Z.; Suleman, R.; Ikram, M.

    2010-10-01

    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.

  2. 5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

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    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.

  3. 5-ALA-mediated photodynamic therapy reduces the parasite load in mice infected with Leishmania braziliensis.

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    Souza, D M; Alves, P M; Silva, M L F; Paulino, T P; Coraspe, H O; Mendonça, M M S; Ribeiro, B M; da Silva, M V; Rodrigues Júnior, V; Rodrigues, D B R

    2017-03-01

    Photodynamic therapy (PDT) has proven to be an effective alternative for the treatment of cutaneous leishmaniasis. Skin lesions consist of ulcers with well-defined raised edges, and granular floor. Th1 immune response is the protective profile in patients infected with Leishmania. In this study, the photodynamic therapy with 5-aminolevulinic acid, the parasitic load, and the modulation of the immune response was evaluated in mice infected with Leishmania braziliensis. Balb/c mice were infected with L. braziliensis and subsequently treated with three sections of PDT. The parasite load and mRNA expression of cytokines (IFN-γ, IL-4, IL-17, IL-22, IL-27, IL-10) and transcription factors (GATA-3, Foxp3 and T-bet) were analysed by quantitative PCR. The parasite load in the treated group was significantly lower than in the untreated group (Pphotodynamic therapy promotes a reduction in parasite load and an increased expression of IFN-γ and T-bet mRNA. © 2016 John Wiley & Sons Ltd.

  4. 5-ALA based photodynamic management of glioblastoma

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    Rühm, Adrian; Stepp, Herbert; Beyer, Wolfgang; Hennig, Georg; Pongratz, Thomas; Sroka, Ronald; Schnell, Oliver; Tonn, Jörg-Christian; Kreth, Friedrich-Wilhelm

    2014-03-01

    Objective: Improvement of the clinical outcome of glioblastoma (GBM) patients by employment of fluorescence and photosensitization on the basis of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX). Methods: In this report the focus is laid on the use of tumor selective PpIX fluorescence for stereotactic biopsy sampling and intra-operative treatment monitoring. In addition, our current concept for treatment planning is presented. For stereotactic interstitial photodynamic therapy (iPDT), radial diffusers were implanted into the contrast enhancing tumor volume. Spectroscopic measurements of laser light transmission and fluorescence between adjacent fibers were performed prior, during and post PDT. Results: PpIX concentrations in primary glioblastoma tissue show high intra- and inter-patient variability, but are usually sufficient for an effective PDT. During individual treatment attempts with 5-ALA based GBM-iPDT, transmission and fluorescence measurements between radial diffusers gave the following results: 1. In some cases, transmission after PDT is considerably reduced compared to the value before PDT, which may be attributable to a depletion of oxygenated hemoglobin and/or diffuse bleeding. 2. PpIX fluorescence is efficiently photobleached during PDT in all cases. Conclusion: iPDT with assessment of PpIX fluorescence and photobleaching is a promising treatment option. Individualization of treatment parameters appears to bear a potential to further improve clinical outcomes.

  5. Study of the efficacy of 5 ALA-mediated photodynamic therapy on human larynx squamous cell carcinoma (Hep2c) cell line

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    Khursid, A.; Atif, M.; Firdous, S.; Zaidi, S. S. Z.; Salman, R.; Ikram, M.

    2010-07-01

    5-aminolevulanic acid (ALA), a precursor of Protoporphyrin IX, was evaluated as an inducer of photodamage on Hep2c, human larynx squamous cell carcinoma, cell line. Porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). The present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) using human larynx cells as experimental model. Hep2c cell line was irradiated with red light (a diode laser, λ = 635 nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of Hep2c cells were studied. The optimal uptake of photosensitizer ALA in Hep-2c cells was investigated by means of spectrometric measurement. Cells viability was determined by means of neutral red assay (NR). It was observed that sensitizer or light doses have no significant effect on cells viability when studied independently. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 7 h in vitro incubation. The photocytotoxic assay showed that light dose of 85 J/cm2 gives effective PDT outcome for Hep2c cell line incubated with 55 μg/ml of 5-ALA with a conclusion that Hep2c cell line is sensitive to ALA-mediated PDT.

  6. Antitumor effect of conditioned media derived from murine MSCs and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer in vitro.

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    Mohammadpour, Hemn; Majidzadeh-A, Keivan

    2015-06-01

    Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photodynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2 cm to achieve a total light dose of 5 Joules (J)/cm(2). Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells (P photodynamic therapy. This study showed that MSCs conditioned media combined with PDT may be useful as a novel treatment modality into the development of therapeutic strategies for treatment of breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

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    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  8. Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

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    Jindra, R H; Kubin, A; Kolbabek, H; Alth, G; Dobrowsky, W

    1999-01-01

    This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

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

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    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.

  10. A Study on the Photobleaching Effect of 5-ALA Conjugated Gold Nanoparticles in a CT26 Tumor Model During Photodynamic Therapy

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    Nafiseh Sobhani

    2012-09-01

    Full Text Available Introduction During the process photodynamic therapy (PDT, bleaching of photosensitizer induced by irradiation and generation of reactive oxygen species (ROS can provide some information concerning the efficiency of treatment. Since gold nanoparticles (GNPs have been highlighted as efficient drug delivery systems, in this study, by utilizing GNPs conjugated with 5 aminolevulinic acid (5-ALA-GNPs, the photobleaching of ALA-induced protoporphyrin IX (PpIX was estimated on a colon carcinoma tumor model. Materials and Methods CT26 tumor models were prepared by subcutaneous injection of 5×105 cells into the right flank of Balb/c inbred mice. To estimate the time required to reach maximum concentration of PpIX in the tumors, the fluorescence signal of PpIX was monitored and PDT was performed by intratumoral injection of 5-ALA-GNPs, GNPs, and 5-ALA in separated groups for 15 min with a cycle of 5 min irradiation and 1 min darkness. The photobleaching rate was calculated from recorded fluorescence signals at the darkness intervals. Results The maximum fluorescence of PpIX was recorded 3 and 5 hr after injection of 5-ALA and 5-ALA-GNPs, respectively. Despite the low PpIX accumulation in tumors receiving conjugate, the photobleaching rate of PpIX was determined to be higher than 5-ALA. The reduction of the fluorescence signal due to 5-ALA-GNPs clearance was higher than that of 5-ALA. Conclusion Administration of 5-ALA-GNPs, intensification of ROS generating and the subsequent elevation of photobleaching results in higher treatment efficiency. Also, more rapid clearance of PpIX has an important implication in clinical application of 5-ALA-GNPs that decreases the undesirable effects on healthy tissues.

  11. Influence of ceramide 2 on in vitro skin permeation and retention of 5-ALA and its ester derivatives, for Photodynamic Therapy

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    Maria Bernadete Riemma Pierre

    2009-03-01

    Full Text Available Photodynamic therapy (PDT based on topical 5-aminolevulinic acid (5-ALA, an endogenous precursor of protoporphyrin, is an interesting approach for the treatment of skin cancer. However, 5-ALA is a hydrophilic molecule and such a characteristic limits its appropriate cutaneous penetration and retention. In this way, more lipophilic molecules, such as esterified 5-ALA derivatives, have been under investigation in order to improve the skin penetration of this molecule. Drug formulation can also alter 5-ALA skin penetration. Therefore, the aim of this work was to study the influence of ceramide 2 - the main lipid of the SC- on the cutaneous delivery of 5-ALA and its ester derivatives in vitro, using Franz diffusion cell. The skin permeation of all studied drugs was decreased in the presence of ceramide, representing a desirable characteristic in order to avoid the risk of systemic side effects. Nevertheless, the SC and [epidermis + dermis] retention after 16 h has also been decreased in the presence of ceramide, as compared to control. In conclusion, ceramide was not a good adjuvant, meaning that research of other vehicles could be useful to improve cutaneous delivery of 5-ALA.A Terapia Fotodinâmica (TFD tópica com um precursor das porfirinas endógenas, o ácido 5-aminolevulínico (5-ALA, constitui uma nova modalidade para o tratamento do câncer de pele. Entretanto, o 5-ALA é uma molécula hidrofílica, o que limita sua penetração e retenção cutânea apropriadas. Moléculas mais lipofílicas, tais como derivados esterificados do 5-ALA, estão sob intensa investigação para melhorar a penetração cutânea desta molécula. A formulação que contém o fármaco também pode alterar a penetração cutânea do 5-ALA. Desta forma, o objetivo deste trabalho foi estudar a influência da ceramida 2 - o principal lipídeo do EC- sobre a penetração cutânea de 5-ALA e seus derivados esterificados usando células de difusão de Franz. A permea

  12. Cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid (5-ALA) in cervical intraepithelial neoplasia (CIN) II with associated human papillomavirus infection: a comparison of preliminary results.

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    Bodner, Klaus; Bodner-Adler, Barbara; Wierrani, Franz; Kubin, Andreas; Szölts-Szölts, Josef; Spängler, Babette; Grünberger, Werner

    2003-01-01

    The optimal treatment of preinvasive cervical lesions is still not clear as all surgical techniques cause substantial cervical stroma destruction with the risk of a possible incompetent cervix. Photodynamic therapy can preserve fertility due to selective tissue destruction. The aim of the present study was to compare the efficacy of cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid in eradicating cervical intraepithelial neoplasia (CIN) II and associated HPV infection. Eleven HPV-positive non-pregnant women were selected for photodynamic therapy (PDT). To be eligible for this procedure superficial cervical PAP smears as well as colposcopic biopsies performed before therapy had to show CIN II with the lesion involving at least 15% of the cervix and being colposcopically visible. The deep endocervical PAP smear had to show normal endocervical epithelium. The next (following each PDT) 11 HPV-positive women with CIN II treated with cold-knife conization were used as a control group. The cervical sampling for HPV DNA was performed 3 months after conization and PDT. Patients were followed-up for 1 year with cytological smears and colposcopy at the outpatient department of the hospital. Follow-up at three months revealed that HPV was eradicated by both techniques in 73%. After 12 months follow-up, 100 vs. 91% (conization vs. PDT) of the patients were disease-free. No systemic side-effects and no local necrosis, sloughing or scarring occurred due to PDT. One patient treated with PDT presented with a relapsing suspicious PAP smear and an abnormal white colposcopic lesion after application of acetic acid 6 months post-PDT. A subsequent conization was performed and revealed a CIN I lesion. No statistically significant differences concerning HPV eradication (p > 0.05) and recurrence (p > 0.05) could be observed between the two methods. The results presented in this study indicate that topical PDT with 5-ALA is in most cases a successful

  13. Laser-mediated photodynamic therapy.

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    Alexiades-Armenakas, Macrene

    2006-01-01

    Photodynamic therapy (PDT) has evolved since its inception at the beginning of the 20th century, when it was defined as an oxygen-dependent reaction between a photosensitizing dye and light. Photosensitizers and light sources have since been continually optimized for distinct applications and tissues. Systemic porphyrins, such as hematoporphyrin, were the first photosensitizers to be used, mostly to treat tumors. The first light sources used were broad-band, noncoherent lights, such as quartz, xenon, tungsten, or halogen lamps. The wavelengths of light chosen were based upon the absorption spectrum of porphyrins: blue because the largest peak is at 400 nm (the Soret band) and red because of its greater penetration depth but lesser absorption at 650 nm (a Q band). Systemic photosensitizers caused prolonged photosensitivity, and broad-band light sources had limitations and side effects. The development of topical photosensitizers, such as 5-aminolevulinic acid, and the advent of lasers in recent years have advanced PDT for cutaneous use. In the 1990s, red lasers were applied to PDT because of their increased skin penetration despite lesser absorption by porphyrins. Broad-band blue light and red light have been studied extensively, the former achieving Food and Drug Administration approval in combination with topical aminolevulinic acid for the treatment of actinic keratosis in 1997. These lasers and light sources caused significant side effects, such as discomfort, erythema, crusting, blistering, and dyspigmentation. The recent application of the long-pulsed pulsed dye laser (595 nm) after topical aminolevulinic acid greatly minimized side effects without compromising efficacy. Long-pulsed pulsed dye laser-mediated PDT has since been shown to be effective in treatment of actinic keratosis, actinic cheilitis, sebaceous hyperplasia, lichen sclerosus, and, most recently, acne vulgaris. Finally, intense pulsed light sources have been introduced to PDT for the treatment

  14. Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

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    Liu, Chengcheng; Zhou, Yingli; Wang, Li; Han, Lei; Lei, Jin'e; Ishaq, Hafiz Muhammad; Nair, Sean P; Xu, Jiru

    2016-04-01

    The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.

  15. Weather conditions and daylight-mediated photodynamic therapy

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    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...

  16. Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

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    Mustafa El-Khatib

    2015-04-01

    Full Text Available Objective: Five-aminolevulinic acid (5-ALA-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2. The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1 cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001. Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT, the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the

  17. Photosensitizers mediated photodynamic inactivation against virus particles.

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    Sobotta, Lukasz; Skupin-Mrugalska, Paulina; Mielcarek, Jadwiga; Goslinski, Tomasz; Balzarini, Jan

    2015-01-01

    Viruses cause many diseases in humans from the rather innocent common cold to more serious or chronic, life-threatening infections. The long-term side effects, sometimes low effectiveness of standard pharmacotherapy and the emergence of drug resistance require a search for new alternative or complementary antiviral therapeutic approaches. One new approach to inactivate microorganisms is photodynamic antimicrobial chemotherapy (PACT). PACT has evolved as a potential method to inactivate viruses. The great challenge for PACT is to develop a methodology enabling the effective inactivation of viruses while leaving the host cells as untouched as possible. This review aims to provide some main directions of antiviral PACT, taking into account different photosensitizers, which have been widely investigated as potential antiviral agents. In addition, several aspects concerning PACT as a tool to assure viral inactivation in human blood products will be addressed.

  18. Kinetics and subcellular localization of 5-ALA-induced PpIX in DHL cells via two-photon excitation fluorescence microscopy.

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    Chen, Rong; Huang, Zufang; Chen, Guannan; Li, Yongzeng; Chen, Xianlian; Chen, Jianxin; Zeng, Haishan

    2008-04-01

    Two-photon excitation fluorescence (TPEF) microscopy was used to measure the 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence in follicular lymphoma DHL cells. Kinetics of 5-ALA-induced PpIX accumulation in DHL cells under various 5-ALA concentrations was studied. We found that during the course of continuous incubation with 5-ALA, the relationship between the DHL cell fluorescence signal and the incubation time showed a biphasic variation. Initially the PpIX signal increased with the incubation time and reached the maximal value at about 3 h, and then it decreased with time during the subsequent incubation period. By labeling the 5-ALA incubated DHL cells with different organelle-specific fluorescence probes: Rhodamine 123 (for mitochondria), DioC6(3) (for endoplasmic reticulum) and LysoTracker Green (for lysosomes) respectively, we found that 5-ALA-induced PpIX was primarily localized in endoplasmic reticulum and mitochondria; its concentration in the lysosome was much lower. The results suggested that 5-ALA could potentially be an effective photosensitizer in photodynamic purging of DHL cells. Two-photon excitation fluorescence microscope is a useful tool for studying 5-ALA-induced PpIX subcellular localization.

  19. Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica.

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    Al-Qahtani, Ahmed; Alkahtani, Saad; Kolli, Bala; Tripathi, Pankaj; Dutta, Sujoy; Al-Kahtane, Abdullah A; Jiang, Xiong-Jie; Ng, Dennis K P; Chang, Kwang Poo

    2016-04-01

    Photodynamic inactivation ofLeishmaniaspp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency againstLeishmania tropicapromastigotes and axenic amastigotesin vitro The uptake of these PCs by bothLeishmaniastages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation ofLeishmaniaspp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitizedLeishmania tropicastrains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ∼650 nm) at a fluence of 1 to 2 J cm(-2) Quantitative fluorescence assays based on the loss of GFP/CFSE from liveLeishmania tropicashowed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay.Leishmania tropicastrains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC50s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation ofLeishmaniaspp. for use as vaccines or vaccine carriers.

  20. Hiporfin-mediated photodynamic therapy in preclinical treatment of osteosarcoma.

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    Sun, Mengxiong; Zhou, Chenghao; Zeng, Hui; Puebla-Osorio, Nahum; Damiani, Elisabetta; Chen, Jian; Wang, Hongsheng; Li, Guodong; Yin, Fei; Shan, Liancheng; Zuo, Dongqing; Liao, Yuxin; Wang, Zhuoying; Zheng, Longpo; Hua, Yingqi; Cai, Zhengdong

    2015-01-01

    This study was carried out to investigate the anti-tumor effect and mechanism of hiporfin-mediated photodynamic therapy (hiporfin-PDT) in osteosarcoma. We found that hiporfin accumulated mainly in the cytoplasm of osteosarcoma cells in a time and concentration-dependent manner. Hiporfin-PDT inhibited the proliferation, induced apoptosis and produced cell cycle arrest at G2M in osteosarcoma cell lines. Hiporfin-PDT increased the expression of cleaved-caspase-3, cleaved PARP-1, Bax and RIP1 while it decreased the expression of Bcl-2; in addition, low concentration of hiporfin increased LC3 conversion. Furthermore, cell death caused by hiporfin-PDT could be rescued by Nec-1 but not by Z-VAD-FMK. Production of reactive oxygen species was increased after hiporfin-PDT. In vivo studies showed a significant decrease in tumor volume and weight after hiporfin-PDT in all three tumor mouse models investigated (subcutaneous and orthotopic). Histological analysis showed widespread cell apoptosis and necrosis after treatment. Immunohistochemistry also showed upregulation of cleaved-caspase-3 and downregulation of Bcl-2 after hiporfin-PDT. These results indicate that hiporfin-PDT exhibits a killing effect in osteosarcoma both in vitro and in vivo, which is associated with apoptosis and necroptosis, while autophagy plays a protective role. All these findings shed light on a potential future clinical use for hiporfin in the treatment of osteosarcoma. © 2015 The American Society of Photobiology.

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

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

    2016-03-01

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

  2. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer.

    Science.gov (United States)

    Inoue, Keiji

    2017-02-01

    Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5-aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low-invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5-aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low-energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low-invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5-aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment-resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5-aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer. © 2017 The Japanese Urological Association.

  3. 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.

  4. 5-氨基酮戊酸光动力疗法联合强脉冲光及LED红光治疗中、重度痤疮疗效观察%Efficacy of 5-ALA Photodynamic Therapy Combined with IPL and LED Red Light in the Treatment of Moderate and Severe Acne

    Institute of Scientific and Technical Information of China (English)

    米希婷; 鲍海平; 郑爱义; 米亚英; 王娟; 武晓华

    2015-01-01

    目的:评价5-氨基酮戊酸光动力技术(ALA-PDT)联合强脉冲光(IPL)和LED红光治疗中、重度痤疮的效果,探讨痤疮治疗的最佳方案。方法用ALA-PDT治疗痤疮21例,治疗3~4次;用ALA-PDT联合IPL治疗痤疮30例,先用ALA-PDT治疗3次后,改用IPL治疗1~2次;用ALA-PDT联合二极管激发(LED)红光治疗痤疮29例,先用ALA-PDT治疗3次后,改用LED红光治疗2~4次。分别于治疗6周、8周及治疗后3月对3种方法治疗痤疮的疗效进行评价,并记录不良反应。结果3种治疗方法于治疗6周、8周及疗后3月的总有效率分别为:ALA-PDT组,76.19%,85.71%,90.48%;ALA-PDT联合IPL组,86.67%,96.67%,96.67%;ALA-PDT联合LED红光组,65.52%,68.97%,65.52%。结论ALA-PDT联合IPL和ALA-PDT二法治疗中、重度痤疮均有较好疗效,但ALA-PDT联合IPL较ALA-PDT具有简化程序、不良反应小等优点,值得临床推广应用。%Objective To evaluate the effect of 5-ALA-PDT combined with IPL and LED red light in the treatment of moderate and severe acne. Methods ALA-PDT treatment of 21 cases of acne, treated 3~4times. ALA-PDT combined with IPL for treatment of 30 cases of acne. First, treated with ALA-PDT 3 times, and then switch to IPL 1~2 times. AL-PDT combined with LED red light for treatment of 29 cases of acne. First, treated with ALA-PDT 3 times, and then switch to LED red light treated 2~4 times. Estimate the ef⁃ficacy of three methods of treatment for 6 weeks, 8 weeks and 3 month after treatment being evaluated, and recorded the adverse reac⁃tions. Rusults The total effective rate of 6 weeks, 8 weeks and 3 months after treatment of the three treatments was:ALA-PDT group:76.19%, 85.71%, 90.48%;ALA-PDT combined with IPL group:86.67%, 96.67%, 96.67%;AL-PDT combined with LED red light group:65.52%, 68.97%, 65.52%. Conclusions Both ALA-PDT and ALA-PDT combined with IPL method have good efficacy in treat⁃ment of moderate and severe

  5. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

    Directory of Open Access Journals (Sweden)

    Sadahiro Kaneko

    2016-01-01

    Full Text Available Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD. Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD.

  6. Merocyanine-540 mediated photodynamic effects on Staphylococcus epidermidis biofilms

    Science.gov (United States)

    Sbarra, Maria Sonia; Di Poto, Antonella; Saino, Enrica; Visai, Livia; Minzioni, Paolo; Bragheri, Francesca; Cristiani, Ilaria

    2009-07-01

    Staphylococci are important causes of nosocomial and medical-device-related infections. Their virulence is attributed to the elaboration of biofilms that protect the organisms from immune system clearance and to increased resistance to phagocytosis and antibiotics. Photodynamic treatment (PDT) has been proposed as an alternative approach for the inactivation of bacteria in biofilms. In this study, we evaluated the antimicrobial activity of merocyanine 540 (MC 540), a photosensitizing dye that is used for purging malignant cells from autologous bone marrow grafts, against Staphylococcus epidermidis biofilms. We evaluated the effect of the combined photodynamic action of MC 540 and 532 nm laser on the viability and structure of biofilms of two Staphylococcus epidermidis strains. Significant inactivation of cells was observed in the biofilms treated with MC-540 and then exposed to laser radiation. Furthermore we found that the PDT effect, on both types of cells, was significantly dependent on both the light-dose and on the impinging lightintensity. Disruption of PDT-treated biofilm was confirmed by scanning electron microscopy (SEM).

  7. 5-ALA-PDT后鼻咽癌裸鼠荷瘤组织VEGF及HIF-1α表达改变的实验研究%Expressions of VEGF and HIF-1α in nasopharyngeal carcinoma tissues of nude mice after 5-ALA-PDT

    Institute of Scientific and Technical Information of China (English)

    谢莹; 韦正波; 张哲; 温文胜; 易翔; 黄光武

    2011-01-01

    OBJECTIVE: To investigate the different expressions of VEGF and HIF-1α in nude mice bearing nasopharyngeal carcinoma after 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT).METHODS: CNE-2 cells were implanted in the right flank of the BALB/c nude mice.When the size of tumor reached 0.1-0.15 cm3 ,the mice were administrated with 5-ALA intratumorally at a dose of 100 mg/kg and 3 - 3.5 h prior to laser irradiation (100 mW/cm2 ,100 J,630 nm), while the mice of the control group were under exposure to the same dose laser without 5-ALA used.VEGF and HIF-1α expressions in tumors in both 5-ALA-PDT and control groups were detected by real-time fluorescent quantitative PCR, immunohistochemistry, Western-blot 24 h and 14 d respectively after the exposure to laser.RESULTS: Both differences of HIF-1α mRNA and protein levels were not significant between the 5-ALA-PDT and control groups(P> 0.05).The expression of VEGF in the 5-ALA-PDT group prominently was down-regulated 14 d after PDT(80% positive rate) ,with slightly up-regulated 24 h after the exposure comparing to control group(40% positive rate).CONCLUSIONS: Down-regulation of VEGF in 14 d after 5-ALA-PDT can be the mechanism of inhibition of the development of NPC.This study shows no significant change of HIF-1α following 5-ALA-PDT.The further study will be clone to identify whether HIF-1α can regulate VEGF after PDT.%目的:探讨5-ALA光动力治疗后,裸鼠体内鼻咽癌组织中VEGF及HIF基因表达的改变.方法:鼻咽癌CNE2细胞接种到BALB/c裸鼠右腋下,当肿瘤长到0.1~0.15 cm3时,将动物随机分成3组,每组10只,局部给予5-ALA100 mg/kg,3~3.5h后激光照射(100 mW/cm2,100 J,630 nm),对照组相等激光剂量照射但不给药.分别用实时荧光定量PCR、免疫组化、蛋白质印迹法检测对照组、5-ALA-PDT后24 h及14 d裸鼠鼻咽癌负荷瘤中 VEGF及HIF-1α表达情况.结果:HIF-1α mRNA、蛋白水平在各组间表达差异无统计学意义,P>0.05,

  8. Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres.

    Science.gov (United States)

    Li, Wei; Guo, Xiaomeng; Kong, Fenfen; Zhang, Hanbo; Luo, Lihua; Li, Qingpo; Zhu, Chunqi; Yang, Jie; Du, Yongzhong; You, Jian

    2017-07-28

    Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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

  10. Comparison of {sup 18}F-FET PET and 5-ALA fluorescence in cerebral gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Floeth, Frank Willi; Sabel, Michael; Steiger, Hans Jakob [Heinrich Heine University, Department of Neurosurgery, Duesseldorf (Germany); Ewelt, Christian; Stummer, Walter [Westfaelische Wilhelms University, Department of Neurosurgery, Muenster (Germany); Felsberg, Joerg; Reifenberger, Guido [Heinrich Heine University, Department of Neuropathology, Duesseldorf (Germany); Stoffels, Gabriele; Langen, Karl-Josef [Medical Imaging Physics, Forschungszentrum Juelich, Institute of Neuroscience and Medicine 4, Juelich (Germany); Coenen, Heinz Hubert [Nuclear Chemistry, Forschungszentrum Juelich, Institute of Neuroscience and Medicine 5, Juelich (Germany)

    2011-04-15

    The aim of the study was to compare presurgical {sup 18}F-fluoroethyl-L-tyrosine ({sup 18}F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. {sup 18}F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for {sup 18}F-FET or Gd and checked for 5-ALA fluorescence. {sup 18}F-FET uptake with a mean tumour to brain ratio {>=}1.6 was rated as positive. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, {sup 18}F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, {sup 18}F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on {sup 18}F-FET PET. There are differences between {sup 18}F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. {sup 18}F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. (orig.)

  11. 5-氨基乙酰丙酸介导的光动力学作用对胃癌细胞MKN-45增殖与凋亡作用的研究%Effect of 5-aminolevulinic acid mediated photodynamic therapy on proliferation and apoptosis of gastric cancer cell line MKN-45

    Institute of Scientific and Technical Information of China (English)

    王晓龙; 魏军; 程立文; 张骞; 闫鹏; 王贵玉

    2016-01-01

    Objective To explore the 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) for proliferation and apoptosis of gastric cancer cell line MKN-45.Methods The human gastric cancer cell line MKN-45 was cultured in vitro.The MTT method was used to detect fixed lighting processing (laser radiation dose fixed for 25.00 J/cm2,5-ALA photosensitizer concentrations were 0 mmol/L,0.25 mmol/L,0.50 mmol/L,1.00 mmol/L,2.00 mmol/L),fixed photosensitizer concentration treatment (5-ALA photosensitizer concentrations fixed to 1.00 mmol/L,laser radiation dose were 0 J/cm2,6.25 J/cm2,12.50 J/cm2,25.00 J/cm2,50.00 J/cm2,100.00 J/cm2) of the cell apoptosis rate,and then fixed 5-ALA photosensitizer 1 mmol/L and selected the control group,5-ALA group,pure illumination group and PDT group.The promoting effect on cell apoptosis was determined by MTT,electron microscope and flow cytometry.The activity of human gastric cancer cells MKN-45 apoptosis related proteins p65 and the downstream gene regulatory protein bcl-2,bax,caspase-3 and caspase-9 were detected by using Western blot method.Results When laser radiation dose was fixed,5-ALA photosensitizer concentrations in promoting gastric cancer cell apoptosis was positively related to the dominant (P < 0.01).When 5-ALA photosensitizer concentration was fixed,laser radiation dose effect had no longer dominant after 25.00 J/cm2 positive correlation (P =0.613).When 5-ALA photosensitizer concentration was fixed in 1 mmol/L,compared to control group,5-ALA group and pure illumination group,the inhibition of the MKN-45 cell proliferation in PDT group was more apparently,apoptosis rate increased obviously,signal pathways in cell apoptosis protein involved in the NF-kappa B p65 expression was reduced,the downstream gene regulation of target protein bcl-2,caspase-3 and caspase-9 expression were reduced,and bax protein expression was increased.Conclusions 5-ALA mediated photodynamic has a strong inhibitory effect on the growth of gastric

  12. Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to exogenous 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment.

    Science.gov (United States)

    Schimanski, Adrian; Ebbert, Lara; Sabel, Michael C; Finocchiaro, Gaetano; Lamszus, Katrin; Ewelt, Christian; Etminan, Nima; Fischer, Johannes C; Sorg, Rüdiger V

    2016-10-01

    Glioblastoma (GBM) is the most frequent and lethal primary brain tumor in adults. Despite multimodal therapy combining resection, radio- and alkylating chemotherapy, disease recurrence is universal and prognosis of patients is poor. Glioblastoma stem-like cells (GSC), which can be grown as neurospheres from primary tumors in vitro, appear to be resistant to the established therapies and are suspected to be the driving force for disease recurrence. Thus, efficacy of emerging therapies may depend on targeting GSC. 5-aminolaevulinic acid-mediated photodynamic therapy (5-ALA/PDT) is a promising therapeutic approach in GBM. It utilizes the selective accumulation of the photosensitizer protoporphyrin IX (PPIX) in GBM cells after application of 5-ALA. When exposed to laser light of 635nm wavelength, PPIX initiates a photochemical reaction resulting in the generation of reactive oxygen species, which kill the tumor cells. Whether GSC accumulate PPIX and are sensitive to 5-ALA/PDT is currently unknown. Therefore, human GSC were derived from primary tumors and grown as neurospheres under serum free conditions. When subjected to exogenous 5-ALA, a dose- and time-dependent accumulation of PPIX in GSC was observed by flow cytometry, which varied between individual GSC preparations. Subsequent exposure to laser light of 635nm wavelength substantially killed GSC, whereas treatment with 5-ALA or exposure to laser light only had no effect. LD50 values differed between GSC preparations, but were negatively correlated with PPIX accumulation in GSC. In summary, we report for the first time that glioblastoma stem-like cells accumulate PPIX when subjected to 5-aminolaevulinic acid and are sensitive to 5-aminolaevulinc acid based photodynamic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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.

  14. mTHPC mediated photodynamic therapy (PDT) of squamous cell carcinoma in the head and neck : A systematic review

    NARCIS (Netherlands)

    de Visscher, S. A. H. J.; Dijkstra, P. U.; Tan, I. B.; Roodenburg, J. L. N.; Witjes, M. J. H.

    2013-01-01

    Objective: Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC). To evaluate available evidence on the use of mTHPC (Foscan (R)) mediated PDT, we conducted a review of the literature. Materials and methods: A systematic review was p

  15. Control of burn wound sepsis in rats by methylene blue-mediated photodynamic treatment

    Science.gov (United States)

    Hasegawa, Hiroyuki; Sato, Shunichi; Kawauchi, Satoko; Saitoh, Daizoh; Shinomiya, Nariyoshi; Ashida, Hiroshi; Terakawa, Mitsuhiro

    2012-02-01

    Control of wound sepsis is an important challenge in traumatology. However, increase in the drug-resistant bacteria makes this challenge considerably difficult in recent years. In this study, we attempted to control burn wound sepsis in rats by photodynamic treatment, which has been reported to be effective against some drug-resistant bacteria. A 20% TBSA (total body surface area) full-thickness burn was made in rat dorsal skin, and five days after injury, a suspension of P. aeruginosa was applied to the wound surface. At 30 min after infection, a methylene blue (MB) solution was applied to the wound surface; 5 min afterwards, the wound was illuminated with a 665-nm light emitting diode (LED) array for 10 min. This treatment (application of MB and illumination) was repeated 3 times successively. The averaged light intensity on the wound surface was 3.3 mW/cm2, the corresponding total light dose being 5.9 J/cm2. One week after injury, the numbers of bacteria in the blood and liver were counted by colony forming assay. In the liver, the number of bacteria of the treated group was significantly lower than that of the sham control group without photodynamic treatment. In the blood, no bacteria were detected in the treated group, while a certain amount of bacteria was detected in the control group. These results demonstrate the efficacy of MB-mediated PDT with a red LED array to control burn wound sepsis.

  16. Potentiation of the photodynamic action of hypericin.

    Science.gov (United States)

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

    2008-01-01

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

  17. 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature

    Directory of Open Access Journals (Sweden)

    Samy Eljamel

    2015-05-01

    Full Text Available Background: Glioblastoma multiforme (GBM is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR rate was 75.4% (95% CI: 67.4–83.5, p < 0.001. The mean time to tumor progression (TTP was 8.1 months (95% CI: 4.7–12, p < 0.001. The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001. The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001 and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001. Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP.

  18. [Two-photon excitation fluorescence of 5-ALA induced PpIX in DHL cells].

    Science.gov (United States)

    Huang, Zu-Fang; Chen, Rong; Li, Yong-Zeng; Chen, Guan-Nan; Chen, Xian-Ling; Feng, Shang-Yuan; Jia, Pei-Min

    2008-11-01

    Two-photon fluorescence microscopy is a novel imaging technique, which is primarily sensitive to a specimen's response coming from an in-focus plane, thus has low photo-bleaching and photo-damage to biological samples. 5-ALA induced production of PpIX in DHL cells was excited by 820 nm femtosecond laser; two-photon excitation fluorescence of single cell was obtained in Lambda mode of laser scanning confocal microscope. The specific fluorescence intensity of PpIX which accumulated in DHL cells was measured at 2, 4 and 10 mmol x L(-1) concentration of 5-ALA with different incubation time, which reflected the kinetics of 5-ALA accumulated in DHL cells. Accumulation of PpIX in DHL cells was a dynamic change process. Biphasic alterations of PpIX accumulation were noted: PpIX content enhanced with the increasing time and reached the maximal value around 3 h, however PpIX content decreased in the subsequent incubation time. Results indicate that two-photon fluorescence based on laser scanning microscope can be a useful technology for studying the kinetics of 5-ALA induced PpIX production in DHL cells and other leukemia cells.

  19. Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy in human pancreatic cancer cell lines.

    Science.gov (United States)

    Khaled, Yazan S; Wright, Kathleen; Melcher, Alan; Jayne, David

    2015-02-26

    Oncolytic viral therapy and photodynamic therapy are potential therapies for inoperable or advanced pancreatic cancer. Our aim was to investigate the anti-cancer killing effects of reovirus therapy combined with protoporphyrin IX (PpIX)-mediated photodynamic therapy on a variety of human pancreatic cancer cell lines. Pancreatic cancer cell lines (PsPC-1 and BXPC-3) and a non-cancer control cell line (HEK293) were infected with reovirus serotype 3 strain Dearing (T3D) at 0, 0·1, 1, and 10 plaque-forming units (PFU) per cell for 48 h. Cells were incubated with PpIX pro-drug 5-aminolevulinic acid (5-ALA) at 0, 1, 2, 3, and 4 mM for 4 h. Then, cells were photo-irradiated for 15 min with visible red light-emitting diodes with a light-fluence of 0·54 J/cm(2) of 653 nm (PpIX optimal excitation wavelength). The killing effects of reovirus combined with PpIX-mediated photodynamic therapy were analysed in methylthiazoltetrazolium (MTT) and trypan blue assays. The effect of adding reovirus after photodynamic therapy was also assessed. The statistical significance of the difference between groups was assessed with the two-tailed Student's t test. pphotodynamic therapy resulted in a significantly increased cytotoxic effect compared with reovirus monotherapy and photodynamic therapy (p=0·042) with 100% cell death observed across pancreatic cell lines with 10 PFU per cell combined with 1 and 2 mM 5-ALA. There was no difference in cytotoxicity observed between added reovirus before or after photodynamic therapy. To our knowledge, this is the first in-vitro study to combine reovirus oncolytic viral therapy with PpIX-mediated photodynamic therapy to treat pancreatic cancer. These results show a significant additive effect in cell killing and they provide initial evidence for a novel combined therapeutic intervention. National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Chlorin e6 mediated photodynamic inactivation for multidrug resistant Pseudomonas aeruginosa keratitis in mice in vivo

    Science.gov (United States)

    Wu, Ming-Feng; Deichelbohrer, Mona; Tschernig, Thomas; Laschke, Matthias W.; Szentmáry, Nóra; Hüttenberger, Dirk; Foth, Hans-Jochen; Seitz, Berthold; Bischoff, Markus

    2017-01-01

    Following corneal epithelium scratches, mouse corneas were infected with the multidrug resistant (MDR) P. aeruginosa strain PA54. 24 hours later, 0% (for control group), 0.01%, 0.05% or 0.1% Chlorin e6 (Ce6), a second generation photosensitizer derived from chlorophyll, was combined with red light, for photodynamic inactivation (PDI). 1 hour or 2 days later, entire mouse eyes were enucleated and homogenized for counting colony forming units (CFU) of P. aeruginosa. For comparison, 0.1% Ce6 mediated PDI was started at 12 hours post infection, and 0.005% methylene blue mediated PDI 24 hours post infection. Clinical scores of corneal manifestation were recorded daily. Compared to the control, CFU 1 hour after PDI started 24 hours post infection in the 0.01% Ce6 and 0.05% Ce6 groups were significantly lower (more than one log10 reduction), the CFU 2 days post PDI higher in the 0.1% Ce6 group, clinical score lower in the 0.1% Ce6 group at 1 day post PDI. These findings suggest that PDI with Ce6 and red light has a transient efficacy in killing MDR-PA in vivo, and repetitive PDI treatments are required to fully resolve the infection. Before its clinical application, the paradoxical bacterial regrowth post PDI has to be further studied. PMID:28295043

  2. WSTO9 (TOOKAD) mediated photodynamic therapy as an alternative modality in the treatment of prostate cancer

    Science.gov (United States)

    Chen, Qun; Huang, Zheng; Luck, David L.; Beckers, Jill; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Hetzel, Fred W.

    2002-06-01

    Photodynamic therapy (PDT) utilizes optical energy to activate a pre-administered photosensitizer drug to achieve a localized tumor control. In the presented study, PDT mediated with a second-generation photosensitizer, WST09 (TOOKAD, Steba Biotech, The Netherlands), is investigated as an alternative therapy in the treatment of prostate cancer. In vivo canine prostate is used as the animal model. PDT was performed by irradiating the surgically exposed prostates both superficially and interstitially with a diode laser (763 nm) to activate the intra-operatively i.v. infused photosensitizer. During light irradiation, tissue optical properties, and temperature were monitored. During the one-week to 3-month period post PDT treatment, the dogs recovered well with little or no complications. The prostates were harvested and subjected to histopathological evaluations. Maximum lesion size of over 3 cm in dimension could be achieved with a single treatment, suggesting the therapy is extremely effective in destroying prostatic tissue. Although we found there was loss of epithelial lining in prostatic urethra, there was no evidence it had caused urinary tract side effects as reported in those studies utilizing transurethral irradiation. In conclusion, we found second generation photosensitizer WST09 mediated PDT may provide an excellent alternative to treat prostate cancer.

  3. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

    Science.gov (United States)

    Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2009-02-01

    Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

  4. 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.

  5. A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

    Science.gov (United States)

    Qiu, Haixia; Kim, Michele M; Penjweini, Rozhin; Finlay, Jarod C; Busch, Theresa M; Wang, Tianhao; Guo, Wensheng; Cengel, Keith A; Simone, Charles B; Glatstein, Eli; Zhu, Timothy C

    2017-07-01

    This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [(1) O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm(-2) ) and in-air fluence rates (50-150 mW cm(-2) ) at Photofrin dosages of 5 and 15 mg kg(-1) and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [(1) O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [(1) O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [(1) O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm(-2) but cannot be predicted with fluence alone. LCR increases with increasing [(1) O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [(1) O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR. © 2017 The American Society of Photobiology.

  6. 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.

  7. Preliminary study of transurethral photodynamic therapy mediated with Tookad in a canine prostate model

    Science.gov (United States)

    Huang, Zheng; Hetzel, Fred W.; Chen, Qun; Dole, Kenneth C.

    2008-02-01

    Background: photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad (pd-bacteriopheophorbide) was investigated as an alternative modality for treating prostate cancer. Our previous studies show that Tookad PDT can induce marked prostatic tissue lesion but minimal urethral lesion. In this study a transurethral procedure was used to evaluate the response of the prostatic urethra to direct urethral irradiation. Materials and Methods: Tookad solution (2.5 mg/ml) was administered (1 mg/kg) through IV catheter by an infusion pump over 10 min. A diffuser fiber (1 cm active length) was inserted into the prostatic urethra. The light irradiation (50 or 100 J/cm) started at 4 min after the onset of drug infusion. Urinalysis was performed for 24 - 48 h post PDT. One week after PDT, prostates (n = 4) were removed at necropsy and subjected to histopathological examination. Results: The cross section of prostates showed severe hemorrhagic and necrotic lesions on the right lobe. The diameter of the lesion, measured from urethra to capsule, was >13 mm for 50 J/cm treatment and >18 mm for 100 J/cm, respectively. Although underlying periurethral lesion was visible, the urethral surface was intact and prostatic urethra was open. Conclusions: The joint point of the diffuser tip and the guide fiber might be bent while passing through the sharp turn at the Ischial Arch, which could affect the light distribution and cause the asymmetric lesion. Nonetheless, the transurethral direct irradiation can induce marked prostatic tissue lesion but minimal urethral lesion.

  8. 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

  9. 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.

  10. 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

  11. Aminolevulinic Acid-Mediated Photodynamic Therapy Causes Cell Death in MG-63 Human Osteosarcoma Cells.

    Science.gov (United States)

    White, Bradley; Rossi, Vince; Baugher, Paige J

    2016-09-01

    The aim of this study was to test the efficacy of aminolevulinic acid-mediated photodynamic therapy (PDT) against the human osteosarcoma cell line MG-63. Osteosarcoma is the most common type of primary malignant bone tumor diagnosed in the United States among adolescents and children. Treatments for osteosarcoma often result in diminished limb use or amputation. Because ALA-mediated PDT exhibits dual specificity in the context of tumor killing, this therapy could represent a less invasive, but effective, treatment for this disease. To assess ALA dark toxicity in MG-63 cells, cells were incubated with varying concentrations of ALA, and cell viability was determined by crystal violet assay. Protoporphyrin IX (PpIX) accumulation was assessed subsequent to ALA incubation at various concentrations using spectrofluorometry. Cell death subsequent to ALA-PDT was determined by illuminating cells at a wavelength of 635 nm at various light intensities subsequent to ALA incubation. Cell viability was assessed using the MTT assay. ALA dark toxicity was observed only at the highest concentrations of 2, 5, and 10 mM. Maximal PpIX concentration was observed at 0.5 and 1 mM ALA, subsequent to a 24-h incubation. Maximal cell death with minimal light toxicity was observed at 0.5 and 1 mM ALA after illumination with 0.6 and 3 J/cm(2) light. Collectively, our data indicate that ALA-PDT can result in the death of MG-64 human osteosarcoma cells in vitro.

  12. Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy apoptosis.

    Science.gov (United States)

    Srivastava, M; Ahmad, N; Gupta, S; Mukhtar, H

    2001-05-04

    Photodynamic therapy (PDT), a promising treatment modality, is an oxidative stress that induces apoptosis in many cancer cells in vitro and tumors in vivo. Understanding the mechanism(s) involved in PDT-mediated apoptosis may improve its therapeutic efficacy. Although studies suggest the involvement of multiple pathways, the triggering event(s) responsible for PDT-mediated apoptotic response is(are) not clear. To investigate the role of Bcl-2 in PDT-mediated apoptosis, we employed Bcl-2-antisense and -overexpression approaches in two cell types differing in their responses toward PDT apoptosis. In the first approach, we treated radiation-induced fibrosarcoma (RIF 1) cells, which are resistant to silicon phthalocyanine (Pc 4)-PDT apoptosis, with Bcl-2-antisense oligonucleotide. This treatment resulted in sensitization of RIF 1 cells to PDT-mediated apoptosis as demonstrated by i) cleavage of poly(ADP-ribose) polymerase, ii) DNA ladder formation, iii) terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, and iv) DEVDase activity. This treatment also resulted in oligonucleotide concentration-dependent decrease in cell viability and down-regulation of Bcl-2 protein with a concomitant increase in apoptosis. However, the level of Bax, a pro-apoptotic member of Bcl-2 family, remained unaltered. In the second approach, an overexpression of Bcl-2 in PDT apoptosis-sensitive human epidermoid carcinoma (A431) cells resulted in enhanced apoptosis and up-regulation of Bax following PDT. In both the approaches, the increased Bax/Bcl-2 ratio was associated with an increased apoptotic response of PDT. Our data also demonstrated that PDT results in modulation of other Bcl-2 family members in a way that the overall ratio of pro-apoptotic and anti-apoptotic member proteins favors apoptosis.

  13. Sae regulator factor impairs the response to photodynamic inactivation mediated by Toluidine blue in Staphylococcus aureus.

    Science.gov (United States)

    Gándara, Lautaro; Mamone, Leandro; Dotto, Cristian; Buzzola, Fernanda; Casas, Adriana

    2016-12-01

    Photodynamic inactivation (PDI) involves the combined use of light and a photosensitizer, which, in the presence of oxygen, originates cytotoxic species capable of inactivating bacteria. Since the emergence of multi-resistant bacterial strains is becoming an increasing public health concern, PDI becomes an attractive choice. The aim of this work was to study the differential susceptibility to Toluidine blue (TB) mediated PDI (TB-PDI) of S. aureus mutants (RN6390 and Newman backgrounds) for different key regulators of virulence factors related to some extent to oxidative stress. Complete bacteria eradication of planktonic cultures of RN6390 S. aureus photosensitized with 13μM TB was obtained upon illumination with a low light dose of 4.2J/cm(2) from a non-coherent light source. Similarly, complete cell death was achieved applying 1.3μM TB and 19J/cm(2) light dose, showing that higher light doses can lead to equal cell death employing low photosensitizer concentrations. Interestingly, RN6390 in planktonic culture responded significantly better to TB-PDI than the Newman strain. We showed that deficiencies in rsbU, mgrA (transcription factors related to stress response) or agr (quorum sensing system involved in copper resistance to oxidative stress) did not modify the response of planktonic S. aureus to PDI. On the other hand, the two component system sae impaired the response to TB-PDI through a mechanism not related to the Eap adhesin. More severe conditions were needed to inactivate S. aureus biofilms (0.5mM TB, 157J/cm(2) laser light). In mutant sae biofilms, strain dependant differential susceptibilities are not noticed.

  14. Reduction of the invasiveness of human glioma cells by ALA-mediated photodynamic therapy

    Science.gov (United States)

    Hirschberg, Henry; Sun, Chung-Ho; Madsen, Steen

    2006-02-01

    Introduction: High grade gliomas are characterised by rapid and invasive growth, that cause massive tissue destruction at both the tumour- brain boarder as well as in regions remote from the tumor core. Eradication or inhibition of infiltrating glioma cells poses a significant clinical challenge that is unlikely to be solved using conventional treatment regimens consisting of ionizing radiation and chemotherapeutic agents. In this study we evaluated the effects of ALA mediated photodynamic therapy (PDT) on the invesivness of human glioma cells migrating from implanted multicell tumor spheroids. Materials and method 3-400nm diameter tumor spheroids, derived from the human glioma cell line ACBT, were implanted into a gel matrix of collagen type I. 24 hours following implantation there was a significant invasion of the surrounding gel by individual tumor cells to an average distance of 400nm. The cultures were incubated in increasing concentrations of ALA (10-1000 ug/ml) for four hours and then exposed to 635nm laser light in a titration of both fluence level and fluence rate. Results Fluences of 25J/cm2 were clearly cytotoxic for both the infiltrating cells as well as the spheroids at all ALA concentrations. Fluence levels of 6J did not stop the spheroid growth or prove cytotoxic to the glioma cells that had previously migrated into the gel, in a majority of cultures but inhibited further migration of the cells by 80-90% compared to control. Conclusion: Measurement of cell survival and cell proliferation indices seemed to indicate a direct migratory inhibition effect on the invading cells and not cytotoxicity as the most likely mechanism for this observation.

  15. Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors

    DEFF Research Database (Denmark)

    Stummer, Walter; Rodrigues, Floriano; Schucht, Philippe

    2014-01-01

    BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we cond......, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.......1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study....

  16. Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects.

    Science.gov (United States)

    Ulybina, Yulia M; Kuligina, Ekatherina Sh; Mitiushkina, Nathalia V; Sherina, Nathalia Yu; Yanus, Grigoriy A; Gorodnova, Tatiana V; Katanugina, Anna S; Koloskov, Andrey V; Togo, Alexandr V; Imyanitov, Evgeny N

    2010-09-01

    Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G>A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75-103years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p=0.000014). This deviation was not observed in 549 middle-aged (18-50years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p=0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between "good" and "bad" gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant.

  17. Involvement of nitric oxide during phthalocyanine (Pc4) photodynamic therapy-mediated apoptosis.

    Science.gov (United States)

    Gupta, S; Ahmad, N; Mukhtar, H

    1998-05-01

    Photodynamic therapy (PDT), a new treatment modality, uses a combination of photosensitizing agent and visible light for the therapy of many solid malignancies. The hallmark of PDT is intracellular oxidative stress mediated by reactive oxygen species, which, through a cascade of events, results in a cell kill that induces apoptosis in some cells. To better understand the mechanism of apoptosis, we hypothesized the role of nitric oxide (NO), which is considered to be involved in a variety of physiological and pathological processes, during PDT. The model photosensitizer we have been working with is a silicon-phthalocyanine compound termed Pc4. Here, we investigated the involvement of NO during Pc4 PDT in PDT of apoptosis-resistant radiation-induced fibrosarcoma (RIF-1) cells and in PDT of apoptosis-sensitive human epidermoid carcinoma (A431) cells. Pc4 PDT resulted in a rapid increase in nitrite production in A431 cells, starting as early as 15 s post-PDT, and showed a progressive increase up to 15 min post-PDT. This increase in nitrite production was observed in cell lysates as well as in the cell culture medium. RIF-1 cells did not show an increase in nitrite production in either the cell lysates or the culture medium. At this time, a majority of the cells were viable. The Western blot analysis also showed a rapid increase in the expression of the constitutive form of NO synthase as early as 15 s post-PDT when compared to that of the controls. This response showed a dose dependency up to 5 min after Pc4 PDT. This observation was confirmed by a [3H]L-citrulline assay, which also showed a similar pattern for constitutive NO-synthase activity. RIF-1 cells did not show any change in protein expression or enzyme activity after the same treatment. These data, for the first time, demonstrate the generation of NO during PDT and suggest that it may be involved in PDT-mediated apoptosis. This may have relevance in improving the therapeutic efficacy of PDT using

  18. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

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

  19. Effect of 5-aminolevulinic acid-mediated photodynamic therapy on human gastric cancer xenografts in nude mice in vivo%5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

    Institute of Scientific and Technical Information of China (English)

    周广军; 黄宗海; 俞金龙; 厉周; 丁涟沭

    2008-01-01

    Objective To investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoreidal mechanism. Methods Cultured MGC-803 human gastric cancer cells were injected below the skins of the nude mice to develop the tumor model. The tumor-bearing nude mice were examined under the Leica LT-9MACIMSYSPULS to detect the fluorescence. The tumor volume of day 1, 3, 7, 14, 21 after treatment were measured, and its histological changes were also studied. The tissues of the tumors in nude mice of the control group, light group, 5-ALA group and PDT group were examined with the electron microscope and apoptosis was detected by TUNEL assay. Results The tumor model was successfully developed. The tumor in the nude mice emited the red fluorescence under the Leica LT-9MACIMSYSPULS. The tumor volumes were (0.189±0.010)cm3, (0.183±0.011)cm3, (0.185±0.019) cm3, (0.182±0.015)cm3 for the control group, light group, 5-ALA group, PDT group, respectively at day 1 after treatment, while at day 3, (0.294±0.010)cm3, (0.280±0.013)cm3, (0.278±0.016)cm3, (0.183±0.014)cm3;at day 7, (0.409±0.016)cm3, (0.411±0.009)cm3, (0.407±0.015)cm3, (0.221±0.008)cm3;at day 14, (0.970±0.055)cm3 (0.976±0.054)cm3, (0.981±0.032)cm3, (0.318±0.005)cm3;at day 21, (1.495±0.059)cm3, (1.513±0.057)cm3, ( 1.524±0.063)cm3, (0.446±0.042)cm3(F=1003.086, P=0.000). The histology demonstrated that most tumor blood vessels were congested and necrosis developed after PDT while not in the control group, light group and 5-ALA group. Necrosis and apoptosis were observed in the cells of the tumors of the PDT group examined by TUNEL and electron microscope while not in the cells of the tumors of the other groups. Conclusions 5-aminolevulinic acid-mediated photodynamic therapy (PDT) can induce injury to human gastric cancer xenografts and inhibit the tumor growth while light only and 5-ALA only can not. 5-aminolevulinic

  20. 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...

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

    DEFF Research Database (Denmark)

    Wiegell, S R; Skødt, V; Wulf, H C

    2014-01-01

    BACKGROUND: Studies have shown that daylight-photodynamic therapy (PDT) is an effective treatment of actinic keratoses, nearly pain free and more convenient for both the clinics and patients. Treatment of basal cell carcinomas (BCCs) is another main indication for PDT. OBJECTIVES: The aim...

  2. Diffuse reflectance spectra measured in vivo in human tissues during Photofrin-mediated pleural photodynamic therapy

    Science.gov (United States)

    Finlay, Jarod C.; Zhu, Timothy C.; Dimofte, Andreea; Friedberg, Joseph S.; Hahn, Stephen M.

    2006-02-01

    Optimal delivery of light in photodynamic therapy (PDT) requires not only optimal placement and power of light sources, but knowledge of the dynamics of light propagation in the tissue being treated and in the surrounding normal tissue, and of their respective accumulations of sensitizer. In an effort to quantify both tissue optical properties and sensitizer distribution, we have measured fluorescence emission and diffuse reflectance spectra at the surface of a variety of tissue types in the thoracic cavities of human patients. The patients studied here were enrolled in Phase II clinical trials of Photofrin-mediated PDT for the treatment of non-small cell lung cancer and cancers with pleural effusion. Patients were given Photofrin at dose of 2 mg per kg body weight 24 hours prior to treatment. Each patient received surgical resection of the affected lung and pleura. Patients received intracavity PDT at 630nm to a dose of 30 J/cm2, as determined by isotropic detectors sutured to the cavity walls. We measured the diffuse reflectance spectra before and after PDT in various positions within the cavity, including tumor, diaphragm, pericardium, skin, and chest wall muscle in 5 patients. The measurements we acquired using a specially designed fiber optic-based probe consisting of one fluorescence excitation fiber, one white light delivery fiber, and 9 detection fibers spaced at distances from 0.36 to 7.8 mm from the source, all of which are imaged via a spectrograph onto a CCD, allowing measurement of radially-resolved diffuse reflectance and fluorescence spectra. The light sources for these two measurements (a 403-nm diode laser and a halogen lamp, respectively) were blocked by computer-controlled shutters, allowing sequential fluorescence, reflectance, and background acquisition. The diffuse reflectance was analyzed to determine the absorption and scattering spectra of the tissue and from these, the concentration and oxygenation of hemoglobin and the local drug uptake

  3. Diffuse reflectance spectra measured in vivo in human tissues during Photofrin-mediated pleural photodynamic therapy

    OpenAIRE

    Finlay, Jarod C.; Zhu, Timothy C.; Dimofte, Andreea; Friedberg, Joseph S.; Hahn, Stephen M.

    2006-01-01

    Optimal delivery of light in photodynamic therapy (PDT) requires not only optimal placement and power of light sources, but knowledge of the dynamics of light propagation in the tissue being treated and in the surrounding normal tissue, and of their respective accumulations of sensitizer. In an effort to quantify both tissue optical properties and sensitizer distribution, we have measured fluorescence emission and diffuse reflectance spectra at the surface of a variety of tissue types in the ...

  4. The use of 5-ALA to assist complete removal of residual non-enhancing part of childhood medulloblastoma

    DEFF Research Database (Denmark)

    Skjøth-Rasmussen, Jane; Bøgeskov, Lars; Sehested, Astrid

    2015-01-01

    PURPOSE: Medulloblastoma is the most common malignant brain tumor in childhood. Radical surgery in the non-metastatic stage is an important factor with respect to overall survival. In this case, 5-aminolevulinic acid (5-ALA) was used at second-look surgery in order to improve surgical results....... METHODS: The child was pretreated with 3 × 4 mg dexamethasone for 4 days prior to the second surgery. At 5 a.m. on the day of surgery, a freshly prepared solution of 5-ALA (20 mg/kg body weight; Medac, Germany) was given orally. RESULTS: At surgery, through the original opening, the vague red fluorescence...... changed from the high-risk medulloblastoma regimen to the standard-risk regimen. CONCLUSIONS: In this particular difficult case of non-contrast-enhancing tumor, 5-ALA was of vital importance to improve rate of resection and change the aggressiveness needed in postsurgery radiation therapy....

  5. 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.

  6. Optical scatter imaging as an apoptosis assay for cells undergoing ALA-mediated photodynamic therapy in vitro

    Science.gov (United States)

    Rossi, Vincent M.; Baugher, Paige J.; Jacques, Steven L.

    2013-02-01

    Aminolevulinic acid (ALA) is converted to protoporphyrin-IX (PpIX) within mitochondria, causing the assumption that ALA-mediated photodynamic therapy (PDT) results in mitochondrial damage and therefore an apoptotic response. Mitochondria within apoptosing cells swell, forming pores in their outer mitochondrial membranes which release cytochrome-c, triggering apoptosis. Optical scatter imaging (OSI) makes use of scattered fields in order to indicate the morphology of subcellular components, and is used here in order to measure changes in mitochondrial size as a response to ALA-mediated PDT. Two images of the same field of view are spatially filtered in the Fourier plane of a 4-F system. Both spatial filters block directly transmitted light, while accepting different angles of scattered light through an adjustable iris. The optical scatter image ratio (OSIR) of the local intensities of these two spatially filtered images is indicative of scattering particle size. Mie theory is used to calculate the predicted OSIR as a function of scattering particle size. In this fashion, the OSI system is calibrated using polystyrene microspheres of know sizes. Comparison of the measured OSIR from cellular images to theoretical values predicted for mitochondria then serves as an indication as to whether cells are apoptosing. Cells are treated at varying concentrations of ALA and varying exposures of 635 nm light and imaged at varying time points in order to develop a broader understanding of an apoptotic response of cells undergoing ALA mediated PDT.

  7. Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premaligant lesions: an in vivo study

    Science.gov (United States)

    Hsu, Yih-Chih; Chiang, Chun-Pin; Chen, Jian Wen; Chen, Ying-Ru; Lee, Jeng-Woei

    2010-02-01

    One of the best strategies to prevent the occurrence of oral cancer is to eliminate oral precancers and block their further malignant transformation. Previous studies showed that photosan-mediated photodynamic therapy (photosan-PDT) is very effective for human head and neck cancers. To avoid the systemic photodynamic toxicity of photosan, this study was designed to use a topical photosan-PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. Twelve 10-week-old male Syrian golden hamsters were used in this study. DMBA was applied to the left buccal pouches thrice a week for 8 to 10 weeks and mineral oil was painted on the right buccal pouches thrice a week for 8 to 10 weeks as the normal controls. Six hamsters were euthanized for tissue harvest. Precancerous lesions of moderate to severe dysplasia were consistently induced and proven by histological examination. These induced precancerous lesions in the remaining 6 hamsters were used for testing the efficacy of topical photosan-PDT. Before PDT, fluorescence spectroscopy was used to determine when protoporphyrine IX (PpIX) reached its peak level in the lesional epithelial cells after topical application of photosan-gel. We found that PpIX reached its peak level in precancerous lesions about 13.5 min after topical application of photosan-gel. The precancerous lesions in 4 hamsters were treated with topical photosan-PDT using the 635-nm LED light once or twice a week. Complete regression of the precancerous lesions was found after 2-4 PDT treatments by visual and histological examination. Our findings indicate that topical photosan-PDT is a very effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.

  8. Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

    Directory of Open Access Journals (Sweden)

    Bentley M Vitória LB

    2001-08-01

    Full Text Available Abstract Background Photodynamic therapy (PDT using 5-aminolevulinic acid (5-ALA is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs in order to optimize its skin delivery in Photodynamic Therapy (PDT of skin cancers. Methods SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. Results Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p Conclusions The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis to be treated by topical PDT of skin cancer.

  9. Selenium enhances the efficacy of Radachlorin mediated-photodynamic therapy in cervical cancer model

    Science.gov (United States)

    Bae, Dong Han; Wen, Lan Ying; Bae, Su Mi; Kang, Uk; Kim, Keun Hee; Jheon, Sang Hoon; Lee, Jeong Sang; Ahn, Woong Shick

    2009-06-01

    Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. Our goal was to investigate the enhanced anti-tumor effects of photodynamic therapy (PDT) plus selenium in TC-1 tumor cells implanted into mice. The MTT assay and tumor growth inhibition study were evaluated at various time intervals after the PDT plus a various dose of selenium. Following Radachlorin injections after 3 hr, the mice were then administrated selenium (2ug/kg b.w.) and then, tumors were treated with external light treatment (300 J/cm2). The selenium was administered daily for 20 days. PDT or selenium was found to be more compared to control groups. Moreover, the PDT combined with selenium demonstrated a significant suppression of tumor growth in vitro and in vivo. The tumor growth by the PDT combined with selenium was significantly reduced. These data suggest that selenium plus PDT can induce a significant tumor suppression response compared with PDT alone. Also, it can be an effective approach to induce anti-cancer therapy strategy.

  10. 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.

  11. Photodynamic therapy mediated by acai oil (Euterpe oleracea Martius) in nanoemulsion: A potential treatment for melanoma.

    Science.gov (United States)

    Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; Longo, João Paulo Figueiró; Silva, Jaqueline Rodrigues; Fascineli, Maria Luiza; de Souza, Paulo; Faria, Fernando; Degterev, Igor Anatolievich; Rodriguez, Anselmo; Carneiro, Fabiana Pirani; Lucci, Carolina Madeira; Escobar, Patricia; Amorim, Rivadávio Fernandes Batista; Azevedo, Ricardo Bentes

    2017-01-01

    Melanoma is the most aggressive and lethal form of skin cancer, responsible for >80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy. Copyright © 2016. Published by Elsevier B.V.

  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 (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

  13. 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.

  14. Diffuse reflectance spectra measured in vivo in human tissues during Photofrin-mediated pleural photodynamic therapy: updated results

    Science.gov (United States)

    Finlay, Jarod C.; Zhu, Timothy C.; Dimofte, Andreea; Friedberg, Joseph S.; Cengel, Keith A.; Hahn, Stephen M.

    2009-02-01

    We present the results of a series of spectroscopic measurements made in vivo in patients undergoing photodynamic therapy (PDT). The patients studied here were enrolled in Phase II clinical trials of Photofrin-mediated PDT for the treatment of non-small cell lung cancer and cancers with pleural effusion. Patients were given Photofrin at dose of 2 mg per kg body weight 24 hours prior to treatment. Each patient received surgical debulking of the tumor followed by intracavity PDT at 630nm to a dose of 60 J/cm2. Dose was monitored continuously using implanted isotropic fiber-based light detectors. We measured the diffuse reflectance spectra before and after PDT in various positions within the cavity, including tumor, diaphragm, pericardium, skin, and chest wall muscle in 10 patients. The measurements were acquired using a specially designed fiber optic-based probe consisting of one fluorescence excitation fiber, one white light delivery fiber, and 9 detection fibers spaced at distances from 0.36 to 7.8 mm from the source, all of which are imaged via a spectrograph onto a CCD, allowing measurement of radially-resolved diffuse reflectance and fluorescence spectra. The absorption spectra were analyzed using an analytical model of light propagation in diffuse media based on the P3 approximation to radiative transport, assuming a known basis set of absorbers including hemoglobin in its oxygenated and deoxygenated forms and Photofrin. We find significant variation in hemodynamics and sensitizer concentration among patients and within tissues in a single patient.

  15. Bacterial photodynamic inactivation mediated by methylene blue and red light is enhanced by synergistic effect of potassium iodide.

    Science.gov (United States)

    Vecchio, Daniela; Gupta, Asheesh; Huang, Liyi; Landi, Giacomo; Avci, Pinar; Rodas, Andrea; Hamblin, Michael R

    2015-09-01

    The inexorable increase of antibiotic resistance occurring in different bacterial species is increasing the interest in developing new antimicrobial treatments that will be equally effective against multidrug-resistant strains and will not themselves induce resistance. One of these alternatives may be photodynamic inactivation (PDI), which uses a combination of nontoxic dyes, called photosensitizers (PS), excited by harmless visible light to generate reactive oxygen species (ROS) by type 1 (radical) and type 2 (singlet oxygen) pathways. In this study, we asked whether it was possible to improve the efficacy of PDI in vitro and in vivo by addition of the inert salt potassium iodide (KI) to a commonly investigated PS, the phenothiazinium dye methylene blue (MB). By adding KI, we observed a consistent increase of red light-mediated bacterial killing of Gram-positive and Gram-negative species in vitro and in vivo. In vivo, we also observed less bacterial recurrence in wounds in the days posttreatment. The mechanism of action is probably due to formation of reactive iodine species that are produced quickly with a short lifetime. This finding may have a relevant clinical impact by reducing the risk of amputation and, in some cases, the risk of death, leading to improvement in the care of patients affected by localized infections.

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

    Science.gov (United States)

    Nissen, Christoffer V; Heerfordt, Ida Marie; Wiegell, Stine R; Mikkelsen, Carsten S; Wulf, Hans C

    2017-01-17

    The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized intra-individual study investigated whether pretreatment with topical 5% 5-fluorouracil (5-FU) enhanced the treatment efficacy of daylight-mediated PDT in 24 patients with AKs on the hands. One hand of each patient was given 7 days of pretreatment with 5-FU twice daily before daylight-PDT, whereas the other hand was treated with daylight-PDT alone. At 3-month follow-up the overall lesion response rate was significantly higher for the combination of 5-FU and daylight-PDT (62.7%) than for daylight-PDT alone (51.8%) (p = 0.001). Furthermore, pain and erythema in relation to treatment were similar in the 2 groups (p = 1.0 and p = 0.2, respectively). Combination therapy is a safe and effective method to improve daylight-PDT for acral AKs.

  17. Photodynamic Therapy

    Science.gov (United States)

    ... Oncol . 2004;5:497-508. Hopper C. Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol . 2000;1:212-219. Huang Z. A review of progress in clinical photodynamic therapy. Technol Cancer Res Treat . 2005;4:283-293. ...

  18. Towards photodynamic therapy with ionizing radiation: nanoparticle-mediated singlet oxygen generation (Conference Presentation)

    Science.gov (United States)

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

    2016-03-01

    Photodynamic therapy (PDT) is a clinically approved method for the treatment of cancer by using singlet oxygen, a highly reactive oxygen generated from a photosensitizer drug upon photoactivation. Limited light penetration depth into to the tissue means that PDT is unsuitable for deep tissue cancer treatments. This can be overcome by using X-ray /gamma rays activated nanoparticles able to trigger the photosensitizer drug and generate singlet oxygen. Additionally, inorganic nanoparticles interact more strongly with X and/or gamma rays than the tissue, allowing to concentrate the effects of radiation near nanoparticle surface and they can also be molecularly targeted to cancer cells. In this work we synthesized and characterized CeF3 nanoparticles, a well-known scintillator material. The nanoparticles were conjugated with Verteporfin, a photosensitizer drug by electrostatic interaction. We assessed the performance of CeF3 and the conjugates to generate singlet oxygen exposed to X-ray radiation. The X-ray singlet oxygen quantum yield of the nanoparticle-photosensitizer system was accurately quantified for the first time. This provided realistic estimates of the singlet oxygen dose taking into consideration the dose partition of the radiation between CeF3 and the tissue. Furthermore, we investigated gold nanoparticle-photosensitizer systems. We confirmed that pure gold nanoparticles itself generate singlet oxygen which is attributed to plasmonic effects. We found enhanced singlet oxygen generation from gold-Rose Bengal conjugates and gold nanorod-verteporfin conjugates. These singlet-oxygen-generating nanomaterials add a new dimension to radiation-assisted PDT.

  19. Anti-tumor immunity of BAM-SiPc-mediated vascular photodynamic therapy in a BALB/c mouse model.

    Science.gov (United States)

    Yeung, Hing-Yuen; Lo, Pui-Chi; Ng, Dennis K P; Fong, Wing-Ping

    2017-02-01

    In recent decades, accumulating evidence from both animal and clinical studies has suggested that a sufficiently activated immune system may strongly augment various types of cancer treatment, including photodynamic therapy (PDT). Through the generation of reactive oxygen species, PDT eradicates tumors by triggering localized tumor damage and inducing anti-tumor immunity. As the major component of anti-tumor immunity, the involvement of a cell-mediated immune response in PDT has been well investigated in the past decade, whereas the role of humoral immunity has remained relatively unexplored. In the present investigation, using the photosensitizer BAM-SiPc and the CT26 tumor-bearing BALB/c mouse model, it was demonstrated that both cell-mediated and humoral adaptive immune components could be involved in PDT. With a vascular PDT (VPDT) regimen, BAM-SiPc could eradicate the tumors of ∼70% of tumor-bearing mice and trigger an anti-tumor immune response that could last for more than 1 year. An elevation of Th2 cytokines was detected ex vivo after VPDT, indicating the potential involvement of a humoral response. An analysis of serum from the VPDT-cured mice also revealed elevated levels of tumor-specific antibodies. Moreover, this serum could effectively hinder tumor growth and protect the mice against further re-challenge in a T-cell-dependent manner. Taken together, these results show that the humoral components induced after BAM-SiPc-VPDT could assist the development of anti-tumor immunity.

  20. Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study.

    Science.gov (United States)

    Maytin, Edward V; Honari, Golara; Khachemoune, Amor; Taylor, Charles R; Ortel, Bernhard; Pogue, Brian W; Sznycer-Taub, Nathaniel; Hasan, Tayyaba

    2012-09-01

    We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis.

  1. Fluorescence behaviour and dural infiltration of meningioma analyzed by 5-ALA based fluorescence: Operating microscope versus mini-spectrometer.

    Science.gov (United States)

    Knipps, Johannes; Beseoglu, Kerim; Kamp, Marcel; Fischer, Igor; Felsberg, Joerg; Neumann, Lisa M; Steiger, Hans-Jakob; Cornelius, Jan F

    2017-08-30

    To compare fluorescence intensity of tumor specimens as measured by a FGS-microscope and a spectrometer, 2.) to evaluate tumor infiltration of dura mater around meningiomas with help of these two different 5-ALA based fluorescence tools and 3.) to correlate fluorescence intensity with histopathological data. In a clinical series menigiomas were resected by 5-ALA fluorescence guided surgery. Fluorescence intensity was semi-quantitatively rated by the surgeon at pre-defined points. Biopsies were harvested and fluorescence intensity measured by a spectrometer and histopathologically analysed. Sampling was realized at the level of the dura in a centrifugal direction. 104 biopsies (n= 13 tumors) were analysed. Specificity and sensitivity of the microscope were 0.96 and 0.53 and of the spectrometer 0.95 and 0.93, respectively. Fluorescence intensity as measured by the spectrometer was correlated to histologically confirmed tumor burden. In a centrifugal direction, tumor burden and fluorescence intensity continuously decreased (along the dural tail). Below a threshold value of 639 arbitrary units no tumor was histologically detectable. At the level of the dura the spectrometer was highly sensitive for detection of meningioma cells. The surgical microscope showed false negative results and missed residual tumor cells in more than half of the cases. The complementary use of both fluorescence tools may improve resection quality. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Combined concurrent nanoshell loaded macrophage-mediated photothermal and photodynamic therapies

    Science.gov (United States)

    Hirschberg, Henry; Trinidad, Anthony; Christie, Catherine E.; Peng, Qian; Kwon, Young J.; Madsen, Steen

    2015-02-01

    Macrophages loaded with gold nanoshells (AuNS), that convert near infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on head and neck squamous cell carcinoma (HNSCC). The results provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.

  3. 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

  4. Disruption of the blood brain barrier following ALA mediated photodynamic therapy

    Science.gov (United States)

    Hirschberg, Henry; Peng, Qian; Uzal, Francisco A.; Chighvinadze, David; Zhang, Michelle J.; Madsen, Steen J.

    2008-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to tumor cells as well as degradation of the blood brain barrier (BBB). We have evaluated the ability of ALA mediated PDT to open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. Materials and Methods: ALA-PDT was performed on non tumor bearing inbred Fisher rats at increasing fluence levels. T2 weighted MRI scans were used to evaluate edema formation and post-contrast T I MRI scans were used to monitor the degree BBB disruption which could be inferred from the intensity and volume of the contrast agent visualized. Results. PDT at increasing fluence levels between 9J and 26J demonstrated an increasing contrast flow rate. No effect on the BBB was observed if 26J of light were given in the absence of ALA. A similar increased contrast volume was observed with increasing fluence rates. The BBB was found to be disrupted 2hrs. following PDT and 80-100% restored 72hrs later. Conclusion: PDT was highly effective in opening the BBB in a limited region of the brain. The degradation of the BBB was temporary in nature, opening rapidly following treatment and significantly restored during the next 72 hrs.

  5. Chlorin e6-Mediated Photodynamic Therapy Suppresses P. acnes-Induced Inflammatory Response via NFκB and MAPKs Signaling Pathway

    Science.gov (United States)

    Wang, Yoon-Young; Ryu, A-Reum; Jin, Solee; Jeon, Yu-Mi; Lee, Mi-Young

    2017-01-01

    Photodynamic therapy (PDT), consisting of photosensitizer, light, and oxygen has been used for the treatment of various diseases including cancers, microbial infections and skin disorders. In this study, we examined the anti-inflammatory effect of chlorin e6-mediated PDT in P. acnes-infected HaCaT cells using photosensitizer chlorin e6 (Ce6) and halogen light. The live and heat-killed P. acnes triggered an upregulation of inflammatory molecules such as iNOS, NO, and inflammatory cytokine in HaCaT cells and mouse model. Ce6-mediated PDT notably downregulated the expression of these inflammatory molecules in vitro and in vivo. Similarly, chlorin e6-mediated PDT was capable of regulating inflammatory response in both live and heat killed S. epidermidis exposed HaCaT cells. Moreover, phosphorylation of p38, JNK, and ERK were reduced by Ce6-mediated PDT. Ce6-mediated PDT also reduced the phosphorylation of IKKα/β, IĸBα and NFκB p65 in P. acnes-stimulated HaCaT cells. In addition, the dramatic increase in the nuclear translocation of NFκB p65 observed upon stimulation with P. acnes was markedly impaired by Ce6-based PDT. This is the first suggestion that Ce6-mediated PDT suppresses P. acnes-induced inflammation through modulating NFκB and MAPKs signaling pathways. PMID:28118375

  6. Early apoptosis and cell death induced by ATX-S10Na ( Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Makoto Mitsunaga; Akihito Tsubota; Kohichi Nariai; Yoshihisa Namiki; Makoto Sumi; Tetsuya Yoshikawa; Kiyotaka Fujise

    2007-01-01

    AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ).METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-XL,were decreased in Bax- and p53-independent manner.CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizingphotosensitizer ATX-S10Na (Ⅱ) are mediated by p53-Bax network and Iow levels of Bcl-2 and Bcl-XL proteins.Our results might help in formulating new therapeutic approaches in photedynamic therapy.

  7. PHOTODYNAMIC DIAGNOSIS AND FLUORESCENCE SPECTROSCOPY IN SUPERFICIAL BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Rusakov

    2009-01-01

    Full Text Available A comprehensive fluorescence technique has been developed to study the urinary bladder mucosa in patients with superficial bladder cancer (BC, by using alasense, white light cystoscopy, fluorescence cytoscopy, and local fluorescence spectroscopy in vivo. Quantification of urothelium fluorescence in the red emission foci of 5-ALA-induced protophorphyrin, with the local autofluorescence intensity being borne in mind, has been shown to increase the specificity of photodynamic diagnosis of superficial BC from 70 to 85% (p ≤ 0.05 and the total accuracy of the technique from 80 to 86%.  

  8. Photodynamic immune modulation (PIM)

    Science.gov (United States)

    North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

    1999-09-01

    Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

  9. Fat tissue histological study at indocyanine green-mediated photothermal/photodynamic treatment of the skin in vivo

    Science.gov (United States)

    Yanina, Irina Yu.; Tuchin, Valery V.; Navolokin, Nikita A.; Matveeva, Olga V.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Altshuler, Gregory B.

    2012-05-01

    Histological slices of skin samples with the subcutaneous adipose tissue after photothermal/photodynamic treatment are analyzed. In the case of subcutaneous indocyanine green injection and 808-nm diode laser exposure of the rat skin site in vivo, the greatest changes in tissue condition were observed. Processes were characterized by dystrophy, necrosis, and desquamation of the epithelial cells, swelling and necrosis of the connective tissue, and widespread necrosis of the subcutaneous adipose tissue. The obtained data are useful for safe layer-by-layer dosimetry of laser illumination of ICG-stained adipose tissue for treatment of obesity and cellulite.

  10. 5-氨基乙酰丙酸介导的光动力学治疗胃癌的实验研究%Effect of photodynamic therapy with 5-aminolevulinic acid on human gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    黄宗海; 周广军; 俞金龙; 厉周; 丁涟沭; 徐如祥; 姜晓丹

    2006-01-01

    目的探讨5-氨基乙酰丙酸(5-ALA)介导的光动力学对人胃癌细胞MGC-803的治疗作用.方法将不同浓度的5-ALA加入细胞培养基中,随之给予相同剂量的激光辐射;之后用固定浓度的5-ALA处理细胞,并给予不同剂量的激光辐射.MTT法测定细胞生存率.结果在相同的辐射剂量下,经0.25、0.5、1.0、2.0、4.0 mmol/L的5-ALA处理的细胞生存率分别为(70.07±5.37)%、(50.04±4.99)%、(34.53±5.30)%、(26.89±4.44)%和23.90%±2.80%,除2.0和4.0 mmol/L5-ALA两组间外,其余各组间具有显著性差异(F=266.39,P<0.001).在相同的5-ALA的浓度下,辐射剂量为6.25、12.5、25.0、50.0、100 J/cm2的细胞生存率分别为(83.50±10.43)%、(67.96±9.23)%、(33.80±8.26)%、(23.31±5.98)%和(14.96±3.50)%,各组之间有显著性差异(F=226.31,P<0.0001).而单用5-ALA处理细胞,对应于其浓度为0.25、0.5、1.0、2.0,和4.0 mmol/L时的细胞生存率分别为(96.46±6.72)%、(97.48±5.27)%、(98.33±6.67)%、(99.47±6.97)%和(95.66±7.72)%,各浓度之间无显著性差异(F=0.79,P=0.5383).单纯激光辐射,其剂量为6.25、12.5、25.0、50.0、100.0 J/cm2时的细胞生存率也无显著性差异(F=0.61,P=0.6551).结论在较低的浓度范围内,5-ALA介导的光动力学治疗对人胃癌MGC-803细胞的杀伤作用随着5-ALA浓度的增加而增加,在较高浓度时则存在饱和现象,杀伤力与光剂量成正比.单纯激光不能产生光动力效应,5-ALA本身对细胞无毒性作用.5-ALA介导的光动力学治疗是很有希望的胃癌治疗方法.%Objective To investigate the effect of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) on MGC-803 human gastric cancer cells in vitro. Methods MGC-803 human gastric cancer cells were treated with 5-ALA at various concentrations followed by laser irradiation. The cells were also treated with 5-ALA at the same concentration before laser exposure at various doses. PDT-induced phototoxicity of the cells was

  11. Comparison of the effect of rose bengal- and eosin Y-mediated photodynamic inactivation on planktonic cells and biofilms of Candida albicans.

    Science.gov (United States)

    Freire, Fernanda; Costa, Anna Carolina Borges Pereira; Pereira, Cristiane Aparecida; Beltrame Junior, Milton; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2014-05-01

    Candida albicans is an opportunistic yeast that can cause oral candidosis through the formation of a biofilm, an important virulence factor that compromises the action of antifungal agents. The objective of this study was to compare the effect of rose bengal (RB)- and eosin Y (EY)-mediated photodynamic inactivation (PDI) using a green light-emitting diode (LED; 532 ± 10 nm) on planktonic cells and biofilms of C. albicans (ATCC 18804). Planktonic cultures were treated with photosensitizers at concentrations ranging from 0.78 to 400 μM, and biofilms were treated with 200 μM of photosensitizers. The number of colony-forming unit per milliliter (CFU/mL) was compared by analysis of variance and Tukey's test (P ≤ 0.05). After treatment, one biofilm specimen of the control and PDI groups were examined by scanning electron microscopy. The photosensitizers (6.25, 25, 50, 200, and 400 μM of EY, and 6.25 μM of RB or higher) significantly reduced the number of CFU/mL in the PDI groups when compared to the control group. With respect to biofilm formation, RB- and EY-mediated PDI promoted reductions of 0.22 log10 and 0.45 log10, respectively. Scanning electron microscopy showed that the two photosensitizers reduced fungal structures. In conclusion, EY- and RB-mediated PDI using LED irradiation significantly reduced C. albicans planktonic cells and biofilms.

  12. Induction of NKG2D ligands and increased sensitivity of tumor cells to NK cell-mediated cytotoxicity by hematoporphyrin-based photodynamic therapy.

    Science.gov (United States)

    Park, Min-Ju; Bae, Jae-Ho; Chung, Joo Seop; Kim, Sun-Hee; Kang, Chi-Dug

    2011-01-01

    Natural killer (NK) cells are important innate effector cells which can irradicate tumor cells through specific interactions between activating receptors on NK cells and their cognate ligands on cancer cells. Recently, it has been known that induction of activating NKG2D ligands including MHC class I chain-related (MIC) and UL16-binding protein (ULBP) families on tumor cells by various stresses makes them more susceptible to NK cell-mediated cytotoxicity. Therefore, it was investigated whether sublethal dose of hematoporphyrin-based photodynamic therapy (PDT) could up-regulate NKG2D ligands on tumor cells and increase the susceptibility of cancer cells against NK cells. Treatment with sublethal dose of hematoporphyrin-based PDT increased mRNA transcription and surface expression of ULBP1 and ULBP2 genes in SNU-1 human gastric tumor cell line and MICA/B, ULBP1, ULBP2 and ULBP3 genes in SW-900 human lung cancer cell line. These results were followed by increased susceptibility of cancer cells to NK cell-mediated cytotoxicity after sublethal PDT, which was abolished by addition of a blocking NKG2D mAb. Therefore, it could be suggested that the effect of hematoporphyrin-based PDT might be mediated in part by the increased susceptibility to NK cells via induction of NKG2D ligands on tumor cells, which survived after treatment with PDT.

  13. The pro-apoptotic and anti-invasive effects of hypericin-mediated photodynamic therapy are enhanced by hyperforin or aristoforin in HT-29 colon adenocarcinoma cells.

    Science.gov (United States)

    Šemeláková, Martina; Mikeš, Jaromír; Jendželovský, Rastislav; Fedoročko, Peter

    2012-12-05

    Photodynamic therapy is a rapidly-developing anti-cancer approach for the treatment of various types of malignant as well as non-malignant diseases. In this study, hypericin-mediated photodynamic therapy (HY-PDT) in sub-optimal dose was combined with hyperforin (HP) or its stable derivative aristoforin (AR) in an effort to improve efficacy on the cellular level. The logic of this combination is based on the fact that both bioactive compounds naturally occur in plants of Hypericum sp. At relatively low concentrations up to 5 μM, hyperforin and aristoforin were able to stimulate onset of apoptosis in HT-29 colon adenocarcinoma cells exposed to HY-PDT, inhibit cell cycle progression, suppress expression of matrixmetalloproteinases-2/-9 together with cell adhesivity, thereby affecting the clonogenic potential of the cells. As the action of aristoforin was more pronounced, in line with our assumption, these changes were also linked in this case with hypericin accumulation and increased ROS generation leading to dissipation of mitochondrial membrane potential in a significant portion of the cells, as well as activation of caspase-3. Comparison of HT-29 cells to another colon adenocarcinoma-derived cell line HCT-116 demonstrated significant differences in sensitivity of different cell lines to PDT, however, accumulated effect of HY-PDT with HP/AR proved similar in both tested cell lines. The presented data may help to elucidate the mechanisms of action for different bioactive constituents of St. John's wort, which are increasingly recognized as being able to regulate a variety of pathobiological processes, thus possessing potential therapeutic properties.

  14. Up-regulation of clusterin during phthalocyanine 4 photodynamic therapy-mediated apoptosis of tumor cells and ablation of mouse skin tumors.

    Science.gov (United States)

    Kalka, K; Ahmad, N; Criswell, T; Boothman, D; Mukhtar, H

    2000-11-01

    Photodynamic therapy (PDT) using the silicon phthalocyanine photo-sensitizer Pc 4 is an oxidative stress associated with the induction of apoptosis in many cancer cells in vitro and in vivo. The mechanisms of PDT-induced tumor cell killing leading to apoptosis are incompletely understood. Clusterin, a widely expressed glycoprotein, is induced in tissues regressing as a consequence of oxidative stress-mediated cell death. Treatment of apoptosis-sensitive human epidermoid carcinoma cells (A431) with PDT resulted in significant up-regulation of clusterin with a maximum at 12 h after treatment, whereas clusterin levels in Pc 4-PDT-treated, apoptosis-resistant, radiation-induced fibrosarcoma (RIF-1) cells remained unchanged. The i.v. administration of Pc 4 to mice bearing chemically or UVB radiation-induced skin papillomas, followed by light application, led to increased clusterin protein expression, peaking 24 h after the treatment, when tumor regression was apparently visible. These data, for the first time, demonstrate the involvement of clusterin in PDT-mediated cell death and during tumor regression. This may have relevance in improving the efficacy of PDT using pharmacological inducers of clusterin.

  15. Killing efficacy of a new silicon phthalocyanine in human melanoma cells treated with photodynamic therapy by early activation of mitochondrion-mediated apoptosis.

    Science.gov (United States)

    Barge, Jérôme; Decréau, Richard; Julliard, Michel; Hubaud, Jean-Claude; Sabatier, Anne-Sophie; Grob, Jean-Jacques; Verrando, Patrick

    2004-01-01

    Photodynamic therapy (PDT) is a promising therapeutic modality that utilizes a combination of a photosensitizer and visible light for the destruction of diseased tissues. Using human-pigmented melanoma cells, we examined the photokilling efficacy of new silicon-phthalocyanines (SiPc) that bore bulky axial substituents. The bis(cholesteryloxy) derivate (Chol-O-SiPc) displayed the best in vitro photokilling efficacy (LD(50) = 6-8 x 10(-9) M) and was seven to nine times more potent than chloro-aluminium Pc (ClAlPc), a known photosensitizer used as a reference. Although Chol-O-SiPc was half as potent as ClAlPc for promoting photo-oxidative membrane damage in a cell-free assay, early events of mitochondrion-mediated apoptosis upon PDT were triggered much faster, as demonstrated by kinetics studies examining cells with permeabilized mitochondrial membranes, cytochrome c release and caspase-9 activation. Inhibition of caspase-9 activity by a substrate analogue argued for its central role in the proapoptotic events leading to cell death by Chol-O-SiPc PDT. In addition, immunoblots showed that Bcl-2 antiapoptotic oncoprotein was not a primary target of Chol-O-SiPc in M3Dau cells treated with PDT. Conclusively, Chol-O-SiPc is a useful new photosensitizer with the property of triggering cell apoptosis mediated by mitochondria.

  16. 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...

  17. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... References Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003; 3(5):380–387. [PubMed Abstract] Wilson BC. Photodynamic therapy for cancer: principles. Canadian Journal of Gastroenterology 2002; ...

  18. Photodynamic therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000906.htm Photodynamic therapy for cancer To use the sharing features on ... type of light to kill cancer cells. How Photodynamic Therapy Works First, the doctors injects a medicine that ...

  19. Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

    Directory of Open Access Journals (Sweden)

    Toshihisa Ishikawa

    2010-01-01

    Full Text Available Accumulating evidence indicates that ATP-binding cassette (ABC transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the ABCG2 gene. Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect patients' responses to photodynamic therapy. Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis.

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

    Directory of Open Access Journals (Sweden)

    Brian C. Wilson

    2015-01-01

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

  1. Assessment of Photodynamic Inactivation against Periodontal Bacteria Mediated by a Chitosan Hydrogel in a 3D Gingival Model

    Directory of Open Access Journals (Sweden)

    Po-Chun Peng

    2016-11-01

    Full Text Available Chitosan hydrogels containing hydroxypropyl methylcellulose (HPMC and toluidine blue O were prepared and assessed for their mucoadhesive property and antimicrobial efficacy of photodynamic inactivation (PDI. Increased HPMC content in the hydrogels resulted in increased mucoadhesiveness. Furthermore, we developed a simple In Vitro 3D gingival model resembling the oral periodontal pocket to culture the biofilms of Staphylococcus aureus (S. aureus, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans, and Porphyromonas gingivalis (P. gingivalis. The PDI efficacy of chitosan hydrogel was examined against periodontal biofilms cultured in this 3D gingival model. We found that the PDI effectiveness was limited due to leaving some of the innermost bacteria alive at the non-illuminated site. Using this 3D gingival model, we further optimized PDI procedures with various adjustments of light energy and irradiation sites. The PDI efficacy of the chitosan hydrogel against periodontal biofilms can significantly improve via four sides of irradiation. In conclusion, this study not only showed the clinical applicability of this chitosan hydrogel but also the importance of the light irradiation pattern in performing PDI for periodontal disease.

  2. Assessment of Photodynamic Inactivation against Periodontal Bacteria Mediated by a Chitosan Hydrogel in a 3D Gingival Model.

    Science.gov (United States)

    Peng, Po-Chun; Hsieh, Chien-Ming; Chen, Chueh-Pin; Tsai, Tsuimin; Chen, Chin-Tin

    2016-11-01

    Chitosan hydrogels containing hydroxypropyl methylcellulose (HPMC) and toluidine blue O were prepared and assessed for their mucoadhesive property and antimicrobial efficacy of photodynamic inactivation (PDI). Increased HPMC content in the hydrogels resulted in increased mucoadhesiveness. Furthermore, we developed a simple In Vitro 3D gingival model resembling the oral periodontal pocket to culture the biofilms of Staphylococcus aureus (S. aureus), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), and Porphyromonas gingivalis (P. gingivalis). The PDI efficacy of chitosan hydrogel was examined against periodontal biofilms cultured in this 3D gingival model. We found that the PDI effectiveness was limited due to leaving some of the innermost bacteria alive at the non-illuminated site. Using this 3D gingival model, we further optimized PDI procedures with various adjustments of light energy and irradiation sites. The PDI efficacy of the chitosan hydrogel against periodontal biofilms can significantly improve via four sides of irradiation. In conclusion, this study not only showed the clinical applicability of this chitosan hydrogel but also the importance of the light irradiation pattern in performing PDI for periodontal disease.

  3. Tumour destruction and proliferation kinetics following periodic, low power light, haematoporphyrin oligomers mediated photodynamic therapy in the mouse tongue.

    Science.gov (United States)

    Pe, M B; Ikeda, H; Inokuchi, T

    1994-05-01

    Photodynamic therapy (PDT) is an experimental modality in the treatment of cancer. It involves photochemical reactions that require the interaction of a photosensitising drug, light and oxygen. The development of an efficient protocol based on assuring oxygen availability through modulation of the incident light power density and its mode of delivery was addressed in this study. An estimated energy dose of 180 J/cm2 of 630 nm light from pulsed Nd:YAG dye laser was delivered 24 h after injection of 10 mg/kg haematoporphyrin oligomers in C3H/HeNCrj mice bearing the transplantable squamous cell carcinoma NR-S1, by either of these light regimens: (1) 5 mJ/cm2/pulse for 30 min, 1 h dark interval, followed by another 30 min exposure to the same power (low power, periodic light regimen) or (2) 15 mJ/cm2/pulse for 20 min (high power, continuous light regimen). Results showed a higher mean percentage area of tumour destruction with the low power, periodic light regimen at 54.34% in contrast to 12.44% of the high power, continuous light regimen 2 days after PDT. Furthermore, the mean bromodeoxyuridine labelling indices of the remaining viable-appearing cancer cells were 27.90 and 42.41, respectively, indicating a smaller tumour growth fraction with the former regimen. These results suggest that use of low power, periodically delivered light increases the antitumour efficacy of PDT.

  4. In vitro study of cell death with 5-aminolevulinic acid based photodynamic therapy to improve the efficiency of cancer treatment

    Science.gov (United States)

    Firdous, S.; Nawaz, M.; Ikram, M.; Ahmed, M.

    2012-03-01

    Photodynamic therapy (PDT) is a kind of photochemo therapeutic treatment that exerts its effect mainly through the induction of cell death. Distinct types of cell death may be elicited by different PDT regimes. In this study, efforts are underway to optimize PDT protocols for improved efficacy and combination of all three PDT mechanisms involved in the different human carcinomas cell narcosis. Our in vitro cell culture experiments with 5-aminolevulanic acid (ALA) a clinically approved photiosensitizer (PS) and 635 nm laser light have yielded promising results, as follow: (1) (human cervical cancer (HeLa) cell line incubated, for 18 h, with 30 μg/ml of 5-ALA, treated with laser light dose of 50 J/cm2 can produce 85% of cell killing (2) human larynx carcinoma (Hep2c) cell line incubated, for 7 h, with 55 μg/ml of 5-ALA, treated with laser light dose of 85 J/cm2 can produce 75% of cell killing (3) human liver cancer (HepG2) cell line incubated, for 22-48 h, with 262 μg/ml of 5-ALA, treated with laser light dose of 120 J/cm2 can produce 95% of cell killing (4) human muscle cancer (RD) cell line incubated, for 47 h, with 250 μg/ml of 5-ALA, treated with laser light dose of 80 J/cm2 can produce 76% of cell killing (5) Human embryonic kidney (HEK293T) cell line incu-bated, for 18 h, with 400 μg/ml of 5-ALA, treated with laser light dose of 40 J/cm2 can produce 82% of cell killing confirming the efficacy of photodynamic therapy.

  5. Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Toshihisa Ishikawa

    2011-09-01

    Full Text Available Photodynamic diagnosis (PDD is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP-binding cassette (ABC transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR analysis to design potent ABCG2-inhibitors.

  6. UV-emitting upconversion-based TiO2 photosensitizing nanoplatform: near-infrared light mediated in vivo photodynamic therapy via mitochondria-involved apoptosis pathway.

    Science.gov (United States)

    Hou, Zhiyao; Zhang, Yuanxin; Deng, Kerong; Chen, Yinyin; Li, Xuejiao; Deng, Xiaoran; Cheng, Ziyong; Lian, Hongzhou; Li, Chunxia; Lin, Jun

    2015-03-24

    Photodynamic therapy (PDT) is a promising antitumor treatment that is based on the photosensitizers that inhibit cancer cells by yielding reactive oxygen species (ROS) after irradiation of light with specific wavelengths. As a potential photosensitizer, titanium dioxide (TiO2) exhibits minimal dark cytotoxicity and excellent ultraviolet (UV) light triggered cytotoxicity, but is challenged by the limited tissue penetration of UV light. Herein, a novel near-infrared (NIR) light activated photosensitizer for PDT based on TiO2-coated upconversion nanoparticle (UCNP) core/shell nanocomposites (UCNPs@TiO2 NCs) is designed. NaYF4:Yb(3+),Tm(3+)@NaGdF4:Yb(3+) core/shell UCNPs can efficiently convert NIR light to UV emission that matches well with the absorption of TiO2 shells. The UCNPs@TiO2 NCs endocytosed by cancer cells are able to generate intracellular ROS under NIR irradiation, decreasing the mitochondrial membrane potential to release cytochrome c into the cytosol and then activating caspase 3 to induce cancer cell apoptosis. NIR light triggered PDT of tumor-bearing mice with UCNPs@TiO2 as photosensitizers can suppress tumor growth efficiently due to the better tissue penetration than UV irradiation. On the basis of the evidence of in vitro and in vivo results, UCNPs@TiO2 NCs could serve as an effective photosensitizer for NIR light mediated PDT in antitumor therapy.

  7. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4+ and CD8+ T cells and can be adoptively transferred to naive recipients.

    Science.gov (United States)

    Yusuf, Nabiha; Katiyar, Santosh K; Elmets, Craig A

    2008-01-01

    Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors but it is also immunosuppressive which may reduce its therapeutic efficacy. The purpose of our study was to elucidate the role of CD4+ and CD8+ T cells in PDT immunosuppression. Using silicon phthalocyanine 4 (Pc4) as photosensitizer, nontumor-bearing CD4 knockout (CD4-/-) mice and their wild type (WT) counterparts were subjected to Pc4-PDT in a manner identical to that used for tumor regression (1 cm spot size, 0.5 mg kg(-1) Pc4, 110 J cm(-2) light) to assess the effect of Pc4-PDT on cell-mediated immunity. There was a decrease in immunosuppression in CD4-/- mice compared with WT mice. We next examined the role of CD8+ T cells in Pc4-PDT-induced immunosuppression using CD8-/- mice following the same treatment regimen used for CD4-/- mice. Similar to CD4-/- mice, CD8-/- mice exhibited less immunosuppression than WT mice. Pc4-PDT-induced immunosuppression could be adoptively transferred with spleen cells from Pc4-PDT treated donor mice to syngenic naive recipients (P PDT-induced immunosuppression but do not affect PDT-induced regression of tumors may prove superior to PDT alone in promoting long-term antitumor responses.

  8. A comparative study of toluidine blue-mediated photodynamic therapy versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus: a randomized clinical controlled trial.

    Science.gov (United States)

    Jajarm, Hasan Hoseinpour; Falaki, Farnaz; Sanatkhani, Majid; Ahmadzadeh, Meysam; Ahrari, Farzaneh; Shafaee, Hooman

    2015-07-01

    Recently, photodynamic therapy (PDT) has been suggested as a new treatment option that is free from side effects for erosive-atrophic oral lichen planus (OLP). The purpose of this study was to compare the effect of toluidine blue-mediated photodynamic therapy (TB-PDT) with local corticosteroids on treatment of erosive-atrophic OLP. In this randomized clinical trial, 25 patients with keratotic-atrophic-erosive oral lichen planus were allocated randomly into two groups. Group 1 (experimental): topical application of toluidine blue with micropipette was applied, and after 10 min, the patients were treated with a 630-nm GaAlAs laser (power density: 10 mW/cm(2)) during two visits. Group 2 (control) used mouthwash diluted with dexamethasone (tab 0/5 in 5 ml water) for 5 min, and then, it was spat out, and after 30 min, the mouth was rinsed with 30 drops of nystatin 100,000 units for 5 min and again spat out. Demographic data, type, and severity of the lesions and pain were recorded before and after treatment and then at the 1-month follow-up visit. Response rate was defined based on changes in intensity of the lesions and pain. In the experimental and control groups, sign scores of changes significantly reduced after treatment respectively (p = 0.021) and (p = 0.002), but between the two groups, no significant difference was observed (p = 0.72). In the experimental (p = 0.005) and control groups (p = 0.001), the intensity of lesions significantly reduced after treatment and there was a significant difference between the two groups (p = 0.001). The mean amount of improvement in pain was significantly greater in the control group compared with the experimental group (p < 0.001) (α = 0.05). Our study showed that TB-PDT with laser was effective in the management of OLP.

  9. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  10. Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in human osteosarcoma cell line MG‑63 through the ROS/JNK signaling pathway.

    Science.gov (United States)

    Tu, Pinghua; Huang, Qiu; Ou, Yunsheng; Du, Xing; Li, Kaiting; Tao, Yong; Yin, Hang

    2016-06-01

    The present study was carried out to investigate the effect and mechanisms of aloe‑emodin (AE)-mediated photodynamic therapy (AE-PDT) on the human osteosarcoma cell line MG-63. After treatment with AE-PDT, the human osteosarcoma cell line MG-63 was tested for levels of viability, autophagy, reactive oxygen species (ROS) and apoptosis and changes in cell morphology with the Cell Counting Kit-8 (CCK‑8), monodansylcadaverine (MDC) and Hoechst staining and transmission electron microscopy. The expression of proteins including LC-3, cleaved caspase-3, Beclin-1, Bcl-2, p-JNK, t-JNK and β-actin was examined with western blotting. AE-PDT significantly inhibited the viability of the MG-63 cells in an AE-concentration- and PDT energy density-dependent manner. Autophagy and apoptosis of MG-63 cells was substantially promoted in the AE-PDT group compared to the control group, the AE alone group and the light emitting diode (LED) alone group. Inhibition of autophagy by 3-methyladenine (3-MA) (5 mM) and chloroquine (CQ) (15 µM) significantly promoted the apoptosis rate and improved the sensitivity of the MG-63 cells to AE-PDT. AE-PDT was found to induce the expression of ROS and p-JNK. ROS scavenger, N-acetyl-L-cysteine (NAC, 5 mM), was able to hinder the autophagy, apoptosis and phosphorylation of JNK, and JNK inhibitor (SP600125, 10 µM) significantly inhibited the autophagy and apoptosis, and attenuated the sensitivity of MG63 cells to AE-PDT. In conclusion, AE-PDT induced the autophagy and apoptosis of human osteosarcoma cell line MG-63 through the activation of the ROS-JNK signaling pathway. Autophagy may play a protective role during the early stage following treatment of AE-PDT.

  11. Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death.

    Science.gov (United States)

    Soler, David C; Ohtola, Jennifer; Sugiyama, Hideaki; Rodriguez, Myriam E; Han, Ling; Oleinick, Nancy L; Lam, Minh; Baron, Elma D; Cooper, Kevin D; McCormick, Thomas S

    2016-06-08

    Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3(+) T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6-59.9%) at Pc 4 doses ranging from 0-300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6-81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300 nM, p PDT exerts an enhanced apoptotic effect on activated CD3(+) T cells that may be exploited in targeting T cell-mediated skin diseases, such as cutaneous T cell lymphoma (CTCL) or psoriasis.

  12. T-cell mediated anti-tumor immunity after photodynamic therapy: Why does it not always work and how can we improve it?

    Science.gov (United States)

    de Freitas, Lucas Freitas; Hamblin, Michael R

    2015-01-01

    Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients. PMID:26062987

  13. Talaporfin-mediated photodynamic therapy for peritoneal metastasis of gastric cancer in an in vivo mouse model: drug distribution and efficacy studies.

    Science.gov (United States)

    Kishi, Kentaro; Yano, Masahiko; Inoue, Masahiro; Miyashiro, Isao; Motoori, Masaaki; Tanaka, Koji; Goto, Kunihito; Eguchi, Hidetoshi; Noura, Shingo; Yamada, Terumasa; Ohue, Masayuki; Ohigashi, Hiroaki; Ishikawa, Osamu

    2010-02-01

    Photodynamic therapy (PDT) is a potential treatment for the peritoneal dissemination of gastric cancer, because its cytotoxicity is limited to superficial lesions. We examined the accumulation of talaporfin in peritoneal metastatic nodules and determined the optimal laser condition for these nodules. We also evaluated the pathological response after therapy. We created a peritoneal metastasis model in nude mice using the MKN-45 EGFP cell line. We evaluated the accumulation of talaporfin in peritoneal metastatic nodules and normal organs by spectrophotometric analysis 2-8 h after i.p. talaporfin. To determine optimal PDT conditions, we treated metastatic nodules and the small intestine using multiple laser doses (2, 5, and 10 J/cm2, respectively). Accumulation of talaporfin was detected in metastatic nodules in higher intensities than in the small intestine. The fluorescent intensity of the peritoneal metastatic nodules gradually decreased dependent on the time interval between the laser treatment and talaporfin administration. Fluorescent intensity in the small intestine decreased more than in the metastatic nodules. The pathological response rates by dose were 52.5% at 2 J/cm2, 43.2% at 5 J/cm2, and 64.4% at 10 J/cm2, respectively, when the laser treatment was used 2 h after talaporfin administration, whereas at 4 h, they were 20.8, 25.5, and 26.2%, respectively. Finally, the recommended treatment conditions were considered to be a 2 J/cm2 laser dose and a 4-h interval in terms of toxicity. Talaporfin-mediated PDT may be an effective treatment modality for patients with advanced gastric adenocarcinoma and metastatic peritoneal nodules.

  14. Influence of methylene blue-mediated photodynamic therapy on the resistance to detachment of streptococcus mutans biofilms from titanium substrata

    Science.gov (United States)

    Sharab, Lina Y.

    In dental settings, as well as in other natural systems, plaque-forming microorganisms develop biofilms in which the microbes become protected via their own phenotypic changes and their polymeric exudates from disinfection by washes and antibiotics. Photodynamic Therapy (PDT) is variably effective against these microorganisms, depending on such factors as whether the bacteria are Gram positive or Gram negative, plaque age and thickness, and internal biofilm oxygen concentration. This investigation applied a novel combination of PDT and water-jet impingement techniques to Streptococcus mutans (ATCC strain 27351)-formed biofilms on commercially pure titanium (cpTi) starting with three different phases (ages) of the bacteria, to examine whether the detachment shear stress --as a signature for the work required for removal of the biofilms- would be affected by prior PDT treatment independently from microbial viability. Biofilms were grown with sucrose addition to Brain Heart Infusion media, producing visible thick films and nearly invisible thin films (within the same piece) having the same numbers of culturable microorganisms, the thicker films having greater susceptibility to detachment by water--jet impingement. Colony-forming-unit (CFU) counts routinely correlated well with results from a spectrophotometric Alamar Blue (AB) assay. Use of Methylene Blue (MB) as a photosensitizer (PS) for PDT of biofilms did not interfere with the AB assay, but did mask AB reduction spectral changes when employed with planktonic organisms. It was discovered in this work that PD-treated microbial biofilms, independently from starting or PS-influenced microorganism viability, were significantly (p<0.05) and differentially more easily delaminated and ultimately removed from their substrata biomaterials by the hydrodynamic forces of water-jet impingement. Control biofilms of varying thickness, not receiving PDT treatment, required between 144 and 228 dynes/cm2 of shear stress to

  15. Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch early cancer lesions: an in vivo study

    Science.gov (United States)

    Hsu, Yih-Chih; Chang, Walter Hong-Shong; Chang, Junn-Liang; Liu, Kuang-Ting; Chiang, Chun-Pin; Liu, Chung-Ji; Chen, Chih-Ping

    2011-03-01

    Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people results in oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when photosan reached its peak level in the lesional epithelial cells after topical application of photosan gel. We found that photosan reached its peak level in cancerous lesions about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose 200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced hamster buccal pouch cancerous lesions.

  16. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  17. Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment using ultra-low doses of near infra-red light.

    Science.gov (United States)

    Vankayala, Raviraj; Lin, Chun-Chih; Kalluru, Poliraju; Chiang, Chi-Shiun; Hwang, Kuo Chu

    2014-07-01

    Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under

  18. Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI

    Science.gov (United States)

    Cao, Jianbo; An, Hengqing; Huang, Xinglu; Fu, Guifeng; Zhuang, Rongqiang; Zhu, Lei; Xie, Jin; Zhang, Fan

    2016-05-01

    Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis

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

    Science.gov (United States)

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

    2016-02-01

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

  20. Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea

    Science.gov (United States)

    Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda

    2003-10-01

    Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.

  1. Comparison between HMME mediated photodynamic therapy using 413nm and 532nm for port wine stains: a mathematical simulation study

    Science.gov (United States)

    Wang, Y.; Gu, Y.; Chen, R.; Xu, L. Q.; Liao, X. H.; Huang, N. Y.; Wang, Y. Y.

    2007-11-01

    Introduction: As it is always difficult to find the optimal combination of photosensitizer and of laser wavelength to achieve selective vascular damage in PWS-PDT, the selective vascular effects of HMME (Hematoporphyrin monomethyl ether) mediated PDT with 413 nm and with 532 nm were compared by mathematical simulation in this study. Materials & Methods: Firstly, distribution of 413 nm, 532 nm light in PWS tissue was simulated by Monte Carlo model. Two energy density groups were set, one is 80mW/cm2x40min for both 413 nm and 532 nm, the other is 80mW/cm2x40min for 532 nm while 80mW/cm2x20min in for 413 nm. Secondly, the productivity of reactive oxygen species (ROS) in target vessels and normal tissue were simulated using a simulation system for PDT of PWS established in our lab, which considering the amount of light and photosensitizer in tissue, the molar extinction coefficient of photosensitizer, and quantum yield of ROS. Concentration of HMME for each wavelength were same. Finally, the productivity of ROS n in target vessels and normal tissue were compared between 413 nm PDT and 532 nm PDT under different energy density. Result: Under the same energy density, ROS productivity in target vessels of 413 nm PDT was significantly higher than that of 532 nm PDT. Moreover, it was still higher at low energy density than that of 532nm PDT with high energy density. Conclusion: HMME mediated PDT using 413 nm has the potential to increase the selective vascular effect of PDT for PWS by shortening treatment time.

  2. Photofrin-mediated photodynamic therapy of chemically-induced premalignant lesions and squamous cell carcinoma of the palatal mucosa in rats

    NARCIS (Netherlands)

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

    1997-01-01

    Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an animal model of chemically-induced epithelial dysplasia and squamous cell carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw Photofrin, and using 100 J/cm(2) incident light at two activation wavelen

  3. 9-Hydroxypheophorbide α-mediated photodynamic therapy induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in Hep-2 cells via ROS-mediated suppression of the ERK pathway.

    Science.gov (United States)

    Zhang, Huankang; Shen, Bo; Swinarska, Joanna T; Li, Wen; Xiao, Kuanlin; He, Peijie

    2014-03-01

    Photodynamic therapy (PDT) is a promising treatment modality for malignant diseases through the generation of reactive oxygen species (ROS). In this study, we assessed the change of migration and invasion of HEp-2 cells after sublethal doses of 9-hydroxypheophorbide α (9-HPbD)-mediated PDT in vitro, and explored the role of ROS in 9-HPbD-PDT-induced anti-metastatic effects in HEp-2 cells. Following PDT, ROS were measured by a fluorescence microscope in both the presence and absence of glutathione (GSH) pretreatment. Wound healing assay, cell migration assay, and matrigel invasion assay were used to evaluate the cellular migration and invasion. Western blot was performed to investigate the signaling pathways that may have been involved. ROS were rapidly generated in 9-HPbD-loaded HEp-2 laryngeal cancer cells by the activation of a diode laser and were significantly inhibited by a 6-h GSH pretreatment. Wound healing assay, cell migration assay, and matrigel invasion assay showed that sublethal PDT significantly suppressed the migration and invasion of HEp-2 cells. GSH decreased the ability of PDT to inhibit the invasion of HEp-2 cells. Western blot analysis showed that PDT significantly inhibited the phosphorylation of MEK1/2 and ERK1/2, and significantly suppressed the expression of MMP-2 and MMP-9 after 24h following the implementation of sublethal PDT, and these efficacies of PDT could be abrogated by GSH pretreatment. 9-HPbD-PDT attenuated the migration and invasion of HEp-2 cells in vitro, which may be related to the down-regulated expression of MMP-2 and MMP-9 via ROS-mediated-inhibition of phosphorylation in the ERK/MEK signaling pathway. Copyright © 2014. Published by Elsevier B.V.

  4. New Photodynamic Therapy Developments

    Science.gov (United States)

    Doiron, Dan

    1988-09-01

    I am going go over photodynamic therapy first, just an overview for those of you not familiar with it, as it is quite different from most of the normal surgical laser applications. Then I will be talking about the various aspects of the technology, and what we feel the market potentials are in the various aspects of the photodynamic therapy.

  5. 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.

  6. Photodynamic therapy with green light for the treatment of vulvar lichen sclerosus - Preliminary results.

    Science.gov (United States)

    Osiecka, B J; Jurczyszyn, K; Nockowski, P; Murawski, M; Ziółkowski, P

    2017-03-01

    The standard treatment for lichen sclerosus (LS) is symptomatic and is primarily based on the chronic use of corticosteroids, sometimes resulting in unsatisfactory effects. Therefore, other non-pharmacological methods are being sought, which are less aggravating for the patient. LS can be treated topically by using photodynamic therapy (PDT) based on 5-aminolevulinic acid (5-ALA). Unfortunately, therapy with the red light is often connected with severe local pain during the illumination. Green light can also be characterised by its ability to turn on photodynamic reactions in cells. The aim of this study was an evaluation into the efficacy and tolerance of 5-ALA-PDT with a green light (540nm±15nm) in 11 patients with chronic LS that were characterised by severe itching. The disease lasted from 1.5 to 4 years. All the patients were treated with three sessions of PDT. Following treatment with PDT, a significant improvement of local status, as well as a reduction of the main symptom (pruritus), were observed. No patient complained of severe pain during the sessions that would have required an interruption of irradiation or local application of analgesics. Our preliminary results of using green light in PDT for superficial skin non-oncological lesions are very promising but require further studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Photodynamic damage study of HeLa cell line using ALA

    Science.gov (United States)

    AlSalhi, M. S.; Atif, M.; AlObiadi, A. A.; Aldwayyan, A. S.

    2011-04-01

    The present study evaluates the photodynamic damage with 5-aminolevulinic acid (5-ALA) using HeLa as experimental model. HeLa cell line was irradiated with red light (He-Ne laser, λ = 632.8 CW nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of HeLa cells were studied. The optimal uptake of photosensitizer ALA in HeLa cells was investigated by means of PpIX fluorescence intensity by exciting the HeLa cell suspension at 450 nm and a detection wavelength set at 690 nm. Cells viability was determined by means of trypan blue solution. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 4 h in vitro incubation. We found that the combination with 5-ALA and laser irradiation leads to time/concentration-dependent increase of cells death and also energy doses-dependent enlarge the cells death. The fluorescence intensity after PDD of carcinoma cells reduce when compared with the control group. The fluorescence emission spectral profiles after PDD of carcinoma cells showed a dip around 425-525 nm when compared with the control group. This may be due to the damage of mitochondria component of cells. The percentage of HeLa cells after PDD shows that the percentage of cells survival rate as function of laser dose (power). Hence it is clear that at 200 μg/ml ALA and 20 mW laser irradiation, more than 70% of HeLa cells were dead after 15 min.

  8. Photosensitizers for photodynamic immune modulation

    Science.gov (United States)

    North, John R.; Boch, Ronald; Hunt, David W. C.; Ratkay, Leslie G.; Simkin, Guillermo O.; Tao, Jing-Song; Richter, Anna M.; Levy, Julia G.

    2000-06-01

    PDT may be an effective treatment for certain immune-mediated disorders. The immunomodulatory action of PDT is likely a consequence of effects exerted at a number of levels including stimulation of specific cell signaling pathways, selective depletion of activated immune cells, alteration of receptor expression by immune and non-immune cells, and the modulation of cytokine availability. QLT0074, a potent photosensitizer that exhibits rapid clearance kinetics in vivo, is in development for the treatment of immune disorders. In comparison to the well-characterized and structurally related photosensitizer verteporfin, lower concentrations of QLT0074 were required to induce apoptosis in human blood T cells and keratinocytes using blue light for photoactivation. Both photosensitizers triggered the stress activated protein kinase (SAPK) and p38 (HOG1) pathways but not extracellularly regulated kinase (ERK) activity in mouse Pam212 keratinocytes. In cell signaling responses, QLT0074 was active at lower concentrations than verteporfin. For all in vitro test systems, the stronger photodynamic activity of QLT0074 was associated with a greater cell uptake of this photosensitize than verteporfin. In mouse immune models, sub-erythemogenic doses of QLT0074 in combination with whole body blue light irradiation inhibited the contact hypersensitivity response and limited the development of adjuvant-induced arthritis. QLT0074 exhibits activities that indicate it may be a favorable agent for the photodynamic treatment of human immune disease.

  9. Photodynamic therapy mediated antiproliferative activity of some metal-doped ZnO nanoparticles in human liver adenocarcinoma HepG2 cells under UV irradiation.

    Science.gov (United States)

    Ismail, Amel F M; Ali, Mamdouh M; Ismail, Laila F M

    2014-09-05

    Photodynamic therapy (PDT) is a promising new modality for the treatment of cancer through generation of reactive oxygen species (ROS). In this work, human liver adenocarcinoma cells HepG2 were treated with zinc oxide nanoparticles (ZnO-NPs), metal-doped-ZnO-NPs: Fe-ZnO-NPs Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs, Silica-coated ZnO-NPs, titanium dioxide nanoparticles (TiO2-NPs), titanium dioxide nano-tubes (TiO2-NTs) and ZnO-NPs/TiO2-NTs nanocomposite under UV irradiation. Doxorubicin was used as a standard drug. The results demonstrated that the ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs showed cytotoxicity against HepG2 cells, with the median growth inhibitory concentrations (IC50) 42.60, 37.20, 45.10, 77.20 and 56.50 μg/ml, respectively, as compared to doxorubicin (IC50: 20.10 μg/ml). Treatment of the cancer cells with ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs resulted in a significant increase in the activity of SOD and the levels of H2O2 and NO than those of control, accompanied with a significant decrease in the activity of CAT and GSH-Px. Also, depletion of reduced GSH, total protein and nucleic acids levels was observed. In conclusion, metal-doped ZnO-NPs may induce antiproliferative effect on HepG2 cells under UV-irradiation due to generation of ROS. Therefore, they could be included in modern clinical trials after in vivo more investigations, using photodynamic therapy technique.

  10. Photodynamic therapy of a 2-methoxyestradiol tumor-targeting drug delivery system mediated by Asn-Gly-Arg in breast cancer

    Directory of Open Access Journals (Sweden)

    Shi J

    2013-04-01

    Full Text Available Jinjin Shi, Zhenzhen Wang, Lei Wang, Honghong Wang, Lulu Li, Xiaoyuan Yu, Jing Zhang, Rou Ma, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People's Republic of ChinaAbstract: Fullerene (C60 has shown great potential in drug delivery. In this study we exploited modified fullerene (diadduct malonic acid-fullerene-Asn-Gly-Arg peptide [DMA-C60-NGR] as an antitumor drug carrier in order to build a new tumor-targeting drug delivery system. We also investigated the synergistic enhancement of cancer therapy using photodynamic therapy (PDT induced by DMA-C60-NGR and 2-methoxyestradiol (2ME. Cytotoxicity tests indicated that DMA-C60-NGR had no obvious toxicity, while our drug delivery system (DMA-C60-2ME-NGR had a high inhibition effect on MCF-7 cells compared to free 2ME. The tumor-targeting drug delivery system could efficiently cross cell membranes, and illumination induced the generation of intracellular reactive oxygen species and DNA damage. Furthermore, DMA-C60-2ME-NGR with irradiation had the highest inhibition effect on MCF-7 cells compared to the other groups. DMA-C60-NGR combined with 2ME showed a good synergistic photosensitization effect for inhibiting the growth of MCF-7 cells, demonstrating that DMA-C60-2ME-NGR may be promising for high treatment efficacy with minimal side effects in future therapy.Keywords: fullerene, drug delivery system, photodynamic therapy, tumor targeting

  11. 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

  12. The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells.

    Science.gov (United States)

    Yang, Pei-Wen; Chiang, Tzu-Hsuan; Hsieh, Ching-Yueh; Huang, Ya-Chuan; Wong, Li-Fan; Hung, Mien-Chie; Tsai, Jui-Chang; Lee, Jang-Ming

    2015-12-01

    Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.

  13. Fluorescence intensity and bright spot analyses using a confocal microscope for photodynamic diagnosis of brain tumors.

    Science.gov (United States)

    Yoneyama, Takeshi; Watanabe, Tetsuyo; Kagawa, Hiroyuki; Hayashi, Yutaka; Nakada, Mitsutoshi

    2017-03-01

    In photodynamic diagnosis using 5-aminolevulinic acid (5-ALA), discrimination between the tumor and normal tissue is very important for a precise resection. However, it is difficult to distinguish between infiltrating tumor and normal regions in the boundary area. In this study, fluorescent intensity and bright spot analyses using a confocal microscope is proposed for the precise discrimination between infiltrating tumor and normal regions. From the 5-ALA-resected brain tumor tissue, the red fluorescent and marginal regions were sliced for observation under a confocal microscope. Hematoxylin and eosin (H&E) staining were performed on serial slices of the same tissue. According to the pathological inspection of the H&E slides, the tumor and infiltrating and normal regions on confocal microscopy images were investigated. From the fluorescent intensity of the image pixels, a histogram of pixel number with the same fluorescent intensity was obtained. The fluorescent bright spot sizes and total number were compared between the marginal and normal regions. The fluorescence intensity distribution and average intensity in the tumor were different from those in the normal region. The probability of a difference from the dark enhanced the difference between the tumor and the normal region. The bright spot size and number in the infiltrating tumor were different from those in the normal region. Fluorescence intensity analysis is useful to distinguish a tumor region, and a bright spot analysis is useful to distinguish between infiltrating tumor and normal regions. These methods will be important for the precise resection or photodynamic therapy of brain tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the athymic nude rat

    Science.gov (United States)

    Varghai, Davood; Covey, Kelly; Sharma, Rahul; Cross, Nathan; Feyes, Denise K.; Oleinick, Nancy L.; Flask, Chris A.; Dean, David

    2008-02-01

    Post-operative verification of the specificity and sensitivity of photodynamic therapy (PDT) is most pressing for deeply placed lesions such as brain tumors. We wish to determine whether Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) can provide a non-invasive and unambiguous quantitative measure of the specificity and sensitivity of brain tumor PDT. Methods: 2.5 x 10 5 U87 cells were injected into the brains of six athymic nude rats. After 5-6 days, the animals received 0.5 mg/kg b.w. of the phthalocyanine photosensitizer Pc 4 via tail-vein injection. On day 7 peri-tumor DCE-MRI images were acquired on a 7T microMRI scanner before and after tail-vein administration of 100 μL gadolinium and 400 μL saline. After this scan the animals received a 30 J/cm2 dose of 672-nm light from a diode laser (i.e., PDT). The DCE-MRI scan protocol was repeated on day 13. Next, the animals were euthanized and their brains were explanted for Hematoxylin and Eosin (H&E) histology. Results: No tumor was found in one animal. The DCE-MRI images of the other five animals demonstrated significant tumor enhancement increase (p tumor necrosis. Discussion: The change in signal detected by DCE-MRI appears to be due to PDT-induced tumor necrosis. This DCE-MRI signal appears to provide a quantitative, non-invasive measure of the outcome of PDT in this animal model and may be useful for determining the safety and effectiveness of PDT in deeply placed tumors (e.g., glioma).

  15. Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

    Science.gov (United States)

    Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

    2007-02-01

    Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PET (μPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

  16. Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with 18F- fluorodeoxy-glucose PET imaging in the Athymic Nude Rat

    Science.gov (United States)

    Varghai, Davood; Cross, Nathan; Spring-Robinson, Chandra; Sharma, Rahul; Feyes, Denise K.; Ahmad, Yusra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

    2007-02-01

    Introduction: We have previously demonstrated the use of phthalocyanine Pc 4 for the photodynamic therapy (PDT) of ectopic human glial tumors in the athymic nude rat brain. We wish to determine whether 18F-fluorodeoxy-glucose ( 18F-FDG) Positron Emission Tomography (PET) imaging can detect the reduction in tumor metabolism that must occur after Pc 4-PDT-induced necrosis. Methods: 2.5 x 10 5 U87 cells were injected into the brains of 12 athymic nude rats. After 7 days of tumor growth, all 12 animals were imaged functionally by 18F-FDG micro-PET (μPET) and structurally by micro-CT and/or micro-MR. These animals received 0.5 mg/kg b.w. Pc 4 via tail-vein injection. One day later the scalp was re-incised and the tumor illuminated with 30 J/cm2 of 672-nm light from a diode laser. The next day these animals were again 18F-FDG μPET imaged. Next, the animals were euthanized and their brains were explanted for H&E histology. Results: Histology showed that tumors in the 6 Pc 4-PDT-treated animals demonstrated necrosis ranging from full to frank (severe). Preliminary analysis showed that 18F-FDG μPET activity in 3 of the 6 non-PDT group (i.e., no tumor necrosis observed) animals was seen to increase 2.28 times following tumor photoirradiation, whereas 18F-FDG μPET activity in 5 of the 6 PDT group (i.e., tumor necrosis observed) animals was seen to increase 1.15 times following tumor photoirradiation. Discussion: The increased 18F-FDG μPET activity in the PDT group was unexpected. We had expected this activity to decrease and are presently investigating the cause of this observation.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage, the inconvenie......Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage...

  18. Daylight photodynamic therapy for actinic keratosis

    DEFF Research Database (Denmark)

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

    2011-01-01

    Photodynamic therapy (PDT) is an attractive therapy for non-melanoma skin cancers including actinic keratoses (AKs) because it allows treatment of large areas; it has a high response rate and results in an excellent cosmesis. However, conventional PDT for AKs is associated with inconveniently long...... 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. Immunosuppressive effects of silicon phthalocyanine photodynamic therapy.

    Science.gov (United States)

    Reddan, J C; Anderson, C Y; Xu, H; Hrabovsky, S; Freye, K; Fairchild, R; Tubesing, K A; Elmets, C A

    1999-07-01

    The purpose of this study was to determine if silicon phthalocyanine 4 (Pc 4), a second-generation photosensitizer being evaluated for the photodynamic therapy (PDT) of solid tumors, was immunosuppressive. Mice treated with Pc 4 PDT 3 days before dinitrofluorobenzene sensitization showed significant suppression of their cell-mediated immune response when compared to mice that were not exposed to PDT. The response was dose dependent, required both Pc 4 and light and occurred at a skin site remote from that exposed to the laser. The immunosuppression could not be reversed by in vivo pre-treatment of mice with antibodies to tumor necrosis factor-alpha or interleukin-10. These results provide evidence that induction of cell-mediated immunity is suppressed after Pc 4 PDT. Strategies that prevent PDT-mediated immunosuppression may therefore enhance the efficacy of this therapeutic modality.

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

    Directory of Open Access Journals (Sweden)

    Lei Xia

    2013-01-01

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

  1. Daylight photodynamic therapy in Scotland.

    Science.gov (United States)

    Cordey, Helen; Valentine, Ronan; Lesar, Andrea; Moseley, Harry; Eadie, Ewan; Ibbotson, Sally

    2017-05-01

    Chronic sun-induced dysplastic skin changes (actinic keratoses) are extremely common in fair-skinned people in Scotland. These changes are a major cause of morbidity and may develop into skin cancer. Actinic keratoses are often extensive and pose a therapeutic challenge as field-directed treatment is required for chronic disease management. One such treatment approach is hospital-based photodynamic therapy, which is a well-established treatment in Scotland for actinic keratoses, using a photosensitiser pro-drug and red LED light irradiation. However, photodynamic therapy using daylight as the activating light source is increasingly and effectively used in continental Europe, but had not been explored in Scotland until we initiated this in 2013. We report our experience of daylight photodynamic therapy in 64 patient-treatment courses and demonstrate that this can be an effective, well-tolerated treatment, which is liked by patients. Our most recent data show that most patients (73%) achieved clearance or at least a good response to treatment and had high levels of satisfaction with daylight photodynamic therapy. Daylight exposure measurements indicated that treatment is feasible in Scotland between April to September. Daylight photodynamic therapy is an important advancement in treatment options for Scottish patients with extensive pre-cancerous field changes and provides opportunities for home-based treatment and increased efficiency of photodynamic therapy services.

  2. Photodynamic treatment of diseases

    Science.gov (United States)

    Thorne, James M.

    1980-09-01

    Certain dyes can be absorbed by biological tissue. If the dye absorbs light there, it can damage the tissue beyond repair. This effect is currently widely used to treat certain skin diseases and will undoubtedly be extended to internal diseases. A limited number of experiments have also shown its effectiveness against cancer in humans. Other dyes in tissue do no damage but merely fluoresce. The characteristics of this fluorescence may, in the future, be used to indicate the site and nature of disease in the body. Current optical technology seems particularly well adapted for use in these emerging areas of medicine. This paper suggests how optical technology, chemistry and clinical medicine may be combined in the photodynamic treatment of disease and forecasts the technological growth rates of the relevant biomedical specialties.

  3. Towards Effective Photothermal/Photodynamic Treatment Using Plasmonic Gold Nanoparticles

    OpenAIRE

    Alla Bucharskaya; Galina Maslyakova; Georgy Terentyuk; Alexander Yakunin; Yuri Avetisyan; Olga Bibikova; Elena Tuchina; Boris Khlebtsov; Nikolai Khlebtsov; Valery Tuchin

    2016-01-01

    Gold nanoparticles (AuNPs) of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT)/photodynamic (PDT) therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. ...

  4. Effect of Hematoporphyrin Monomethyl Ether Mediated Photodynamic Therapy on Mice Contact Hypersensitivity%血卟啉单甲醚光动力学疗法对小鼠接触性超敏反应的抑制效应

    Institute of Scientific and Technical Information of China (English)

    邱海霞; 刘红梅; 顾瑛; 李德生; 曾耀英; 何贤辉; 刘丽红

    2008-01-01

    目的 探讨血卟啉单甲醚光动力学疗法(hematoporphyrin monomethyl ether mediated photodynamic therapy,HMME-PDT)对小鼠接触性超敏反应(contact hypersensitivity,CHS)的影响.方法 雌性BALB/c小鼠按功率密度分为50和100mW/cm2两个实验组,同时设置单纯照光组、单纯光敏剂组、空白对照组以及DNFB组.PDT处理后3 d,各实验组分别以2,4-二硝基氟苯(DNFB)诱发小鼠右耳变应性接触性皮炎,以游标卡尺测量发敏前后右耳的厚度差;对于功率密度为50 mW/cm2组,进一步观察了PDT处理前4 d或PDT处理后1、3和12 d,DNFB发敏前后小鼠右耳的厚度差,并对PDT后3 d组行组织学检查,以目镜网格测微尺计算浸润炎症细胞数量.结果 处理前4d预先以DNFB致敏,PDT对CHS无抑制作用(P>0.05).反之,PDT照射后1、3或12 d再以DNFB致敏,则PDT能对CHS产生显著抑制作用(P<0.01),其抑制率分别为58%,63%,47%.且无论是以50mW/cm2还是以100mW/cm2功率密度的激光照射,这种抑制作用均存在.未经任何干预,DNFB致敏组致敏右耳浸润的单核细胞和中性粒细胞的数量增加,而经PDT处理后,浸润的炎性细胞明显减少,二者之间存在显著性差异(P<0.01).结论 HMME-PDT能对正常小鼠接触性超敏反应产生明显抑制作用,并有短暂持续效应.

  5. 5-氨基酮戊酸光动力学疗法在皮肤科的应用进展%Applied advances of 5-aminolevulinic acid photodynamic therapy in dermatology

    Institute of Scientific and Technical Information of China (English)

    张立坤; 竺炯; 张萍

    2012-01-01

    To explore the mechanism and application of photodynamic therapy using aminolevulinic acid (5-ALA) in skin diseases, and provide reference for the rational use in clinic. Summarize the reported articles of mechanism and clinical application of photodynamic therapy in recent ten years, analysis the mechanism in the photodynamic therapy treatment for various skin disease, sort the types of skin disease cured by photodynamic therapy and the side effect related with photodynamic therapy. Photodynamic therapy have good clinical curative effect in skin cancer, erythema scaly skin neoplasms, psoriasis, viral warts, acne, nevus flammeus, etc. and have fewer adverse reactions. Photodynamic therapy is a safe, efficient treatment of psoriasis, and have great application prospects in skin diseases.%探讨5-氨基酮戊酸(ALA)光动力学疗法(PDT)治疗皮肤病的作用原理及应用范围,为临床合理使用ALA-PDT提供参考依据.对近10余年来文献报道的有关PDT研究进展及其临床应用的文献进行总结和分析,综述ALA-PDT治疗各类皮肤病的作用原理和机制,以及ALA-PDT治疗皮肤病的范围,所引起的不良反应.PDT对皮肤肿瘤、红斑鳞屑性皮肤病、人乳头瘤病毒(HPV)感染性皮肤病、痤疮、鲜红斑痣等均有良好的临床效果,不良反应相对较小,在皮肤科有很大的应用前景.

  6. Photodynamic Effect of Ni Nanotubes on an HeLa Cell Line.

    Directory of Open Access Journals (Sweden)

    Muhammad Hammad Aziz

    Full Text Available Nickel nanomaterials are promising in the biomedical field, especially in cancer diagnostics and targeted therapy, due to their distinctive chemical and physical properties. In this experiment, the toxicity of nickel nanotubes (Ni NTs were tested in an in vitro cervical cancer model (HeLa cell line to optimize the parameters of photodynamic therapy (PDT for their greatest effectiveness. Ni NTs were synthesized by electrodeposition. Morphological analysis and magnetic behavior were examined using a Scanning electron microscope (SEM, an energy dispersive X-ray analysis (EDAX and a vibrating sample magnetometer (VSM analysis. Phototoxic and cytotoxic effects of nanomaterials were studied using the Ni NTs alone as well as in conjugation with aminolevulinic acid (5-ALA; this was performed both in the dark and under laser exposure. Toxic effects on the HeLa cell model were evaluated by a neutral red assay (NRA and by detection of intracellular reactive oxygen species (ROS production. Furthermore, 10-200 nM of Ni NTs was prepared in solution form and applied to HeLa cells in 96-well plates. Maximum toxicity of Ni NTs complexed with 5-ALA was observed at 100 J/cm2 and 200 nM. Up to 65-68% loss in cell viability was observed. Statistical analysis was performed on the experimental results to confirm the worth and clarity of results, with p-values = 0.003 and 0.000, respectively. Current results pave the way for a more rational strategy to overcome the problem of drug bioavailability in nanoparticulate targeted cancer therapy, which plays a dynamic role in clinical practice.

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

    Directory of Open Access Journals (Sweden)

    Hoffmann, Gerd

    2004-10-01

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

  8. [Photodynamic therapy for actinic cheilitis].

    Science.gov (United States)

    Castaño, E; Comunión, A; Arias, D; Miñano, R; Romero, A; Borbujo, J

    2009-12-01

    Actinic cheilitis is a subtype of actinic keratosis that mainly affects the lower lip and has a higher risk of malignant transformation. Its location on the labial mucosa influences the therapeutic approach. Vermilionectomy requires local or general anesthetic and is associated with a risk of an unsightly scar, and the treatment with 5-fluorouracil or imiquimod lasts for several weeks and the inflammatory reaction can be very intense. A number of authors have used photodynamic therapy as an alternative to the usual treatments. We present 3 patients with histologically confirmed actinic cheilitis treated using photodynamic therapy with methyl aminolevulinic acid as the photosensitizer and red light at 630 nm. The clinical response was good, with no recurrences after 3 to 6 months of follow-up. Our experience supports the use of photodynamic therapy as a good alternative for the treatment of actinic cheilitis.

  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. Low Power Photodynamic Therapy for Retinoblastoma Mediated by Reactive Oxidative Damage%低剂量光动力诱导活性氧产生治疗视网膜母细胞瘤

    Institute of Scientific and Technical Information of China (English)

    许善超; 陆翠霞; 周非凡

    2012-01-01

    Retinoblastoma ( RB ) is the most common primary intraocular malignancy of infancy, traditional chemotherapy or brachytherapy may induce secondary sarcoma. Photodynamic therapy ( PDT ), a non-invasive selective therapy may be preferable. In this study, we observed the photodynamic effect of different dosages of PPa on Y79 cells through detecting the ROS production and corresponding cell apoptosis. The results indicated that the ROS production and corresponding cell apoptosis ratio increased obviously with an escalating PPa dosage (0.2 、0.4、0. 6 μmol/L ), it is a primary proof of the feasibility of PPa-based photodynamic therapy for retinoblastoma cells killing.%视网膜母细胞瘤(Retinoblastoma,RB)是一种最常见的儿童眼癌,传统的化疗和放疗可能会诱发二次肿瘤的产生.光动力疗法(photodynamic therapy,PDT)作为一种具有选择性的非入侵疗法在肿瘤治疗中展现了很好的应用前景.本课题通过实验观察了不同浓度焦脱镁叶绿酸-a(PPa)光动力作用对人视网膜母细胞瘤细胞株Y79细胞ROS产率和相应诱导凋亡能力的影响.结果表明,伴随逐步上升的PPa浓度(0.2、0.4、0.6 μmol/L ),Y79细胞的ROS产量和相对的凋亡率都明显上升,初步证明了PPa光动力杀伤视网膜母细胞瘤的可行性.

  11. [Photodynamic therapy in gastroenterology].

    Science.gov (United States)

    Shim, Chan Sup

    2005-03-01

    Photodynamic therapy (PDT) was first used for the treatment of esophageal cancer in early 1980s, Since then, numerous applications have been reported for its use in gastrointestinal tract including Barrett's esophagus, gastric, duodenal, biliary, pancreatic and colorectal lesions. PDT in gastroenterology has made tremendous progress over the last decade but its clear role is yet to be proved. Now, there is an increasing need for less invasive methods of treatment in patients with pre-malignant disease, early cancer or those who are unfit for surgery. It is one of a number of ablative techniques currently under investigation and appears to have a number of potential advantages over other forms of treatment in the alimentary tract. The development of newer potent, highly efficient photosensitizers, as well as endoscopic imaging techniques and light delivery systems, are continuing to expand the clinical uses of PDT. As data from additional clinical trials become available, we will gain a clearer perspective of where PDT fits in the treatment of cancers.

  12. A study on clinical efifcacy of two kinds of concentration of 5-Aminolevulinic acid photodynamic therapy in treatment of moderate to severe acne%两种浓度5-氨基酮戊酸光动力疗法治疗中重度痤疮疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘海波; 王雪松

    2016-01-01

    目的:探讨两种浓度5-氨基酮戊酸光动力疗法(ALA-PDT)治疗中重度痤疮的有效性及安全性。方法:将68例中重度痤疮患者随机分为两组:低浓度组:31例,给予5%ALA-PDT治疗;高浓度组:37例,给予10%ALA-PDT治疗,两组均每2周治疗1次,共治疗3次。在治疗后第2、4、6周对两组患者进行疗效判断和比较,同时记录治疗过程中出现的不良反应。结果:31例接受5%ALA-PDT治疗的患者经3次治疗后,总有效率87.10%;37例接受10%ALA-PDT治疗的患者经3次治疗后,总有效率为94.59%,两组疗效相比无统计学意义(P>0.05)。结论:5%ALA封包组与10%ALA封包组疗效相比无统计学意义,但低浓度组红斑、水肿、色素沉着等不良反应小。%Objective To study the safety and efifcacy of two kinds of concentrations of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) in the treatment of moderate to severe acne. Methods 68 patients with moderate to severe acne were randomly divided into two groups:31 cases in low concentration group were treated with 5%5-ALA followed by red laser irradiation with a photodynamic therapy device;37 patients in high concentration group were treated with 10%5-ALA followed by red laser irradiation with a photodynamic therapy device. Patients in both groups were treated once every two weeks, 3 times totally. The patients were followed up 2, 4, and 6 weeks after the treatment, the therapeutic effects in two groups were compared and the adverse reactions were recorded. Results After 3 times treatments, the total effective rates of low and high concentration groups were respectively 87.1%and 94.59%. There was no signiifcant difference between the two groups (P>0.05). Conclusion The clinical efifcacy has no signiifcant difference between 5%5-ALA group and 10%5-ALA group, but the cases with adverse reactions in 5%5-ALA group, such as erythema, oedema, hyperpigmentation, were less.

  13. Medical complex for photodynamic therapy

    Science.gov (United States)

    Soldatov, Anatoly N.; Domanov, Michail S.; Lyabin, Nikolay A.; Chursin, Alexandr D.; Mirza, Sergey Y.; Sukhanov, Viktor B.; Polunin, Yu. P.; Ivanov, Aleksandr I.; Kirilov, Anatoly E.; Rubanov, Sergey N.

    2002-03-01

    Experimental results of initial testing dye-laser 'MLK-02' pumped by a copper vapor laser 'Kulon-10' are presented. Output parameters obtained are the following: average power - 1 and 1.5 W, efficiency - 17.6 and 18.7% at the wavelengths of 670 and 725 nm, respectively. The laser apparatus is supposed to be used for methods of photodynamic therapy.

  14. Photodynamic therapy in clinical practice

    Directory of Open Access Journals (Sweden)

    E. V. Filonenko

    2016-01-01

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

  15. Photodynamic therapy 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

  16. Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources

    DEFF Research Database (Denmark)

    Lerche, Catharina; Heerfordt, Ida M; Heydenreich, Jakob

    2016-01-01

    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...

  17. 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

  18. 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...

  19. Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections.

    Science.gov (United States)

    Barra, Federica; Roscetto, Emanuela; Soriano, Amata A; Vollaro, Adriana; Postiglione, Ilaria; Pierantoni, Giovanna Maria; Palumbo, Giuseppe; Catania, Maria Rosaria

    2015-08-28

    Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O₂, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores.

  20. Interstitial photodynamic therapy and glioblastoma: light fractionation study on a preclinical model: preliminary results

    Science.gov (United States)

    Leroy, Henri-Arthur; Vermandel, Maximilien; Tétard, Marie-Charlotte; Lejeune, Jean-Paul; Mordon, Serge; Reyns, Nicolas

    2015-03-01

    Background Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a local treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen to form cytotoxic species. Fractionation of light delivery may enhance treatment efficiency by restoring tissue oxygenation. Objectives To evaluate the efficiency of light fractionation using MRI imaging, including diffusion and perfusion, compared to histological data. Materials and Methods Thirty-nine "Nude" rats were grafted with human U87 cells into the right putamen. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomized in three groups: without illumination, with monofractionated illumination and the third one with multifractionated light. Treatment effects were assessed with early MRI including diffusion and perfusion sequences. The animals were eventually sacrificed to perform brain histology. Results On MRI, we observed elevated diffusion values in the center of the tumor among treated animals, especially in multifractionated group. Perfusion decreased around the treatment site, all the more in the multifractionated group. Histology confirmed our MRI findings, with a more extensive necrosis and associated with a rarified angiogenic network in the treatment area, after multifractionated PDT. However, we observed more surrounding edema and neovascularization in the peripheral ring after multifractionated PDT. Conclusion Fractionated interstitial PDT induced specific tumoral lesions. The multifractionated scheme was more efficient, inducing increased tumoral necrosis, but it also caused significant peripheral edema and neovascularization. Diffusion and perfusion MRI imaging were able to predict the histological lesions.

  1. 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...

  2. 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.

  3. Treatment of rheumatoid arthritis using photodynamic therapy

    Science.gov (United States)

    Hendrich, Christian; Diddens, Heyke C.; Nosir, Hany R.; Siebert, Werner E.

    1995-03-01

    The only early therapy of rheumatoid arthritis in orthopedic surgery is a synovectomy, which is restricted to more or less big joints. A laser-synovectomy of small joints is ineffective yet. An alternative method may be photodynamic therapy. In our study we describe the photodynamic effect of Photosan 3 in a cell culture study.

  4. Photodynamic therapy in endodontics: a literature review.

    Science.gov (United States)

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

    2015-03-01

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

  5. 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

  6. Clinical efficacy of photodynamic therapy

    Science.gov (United States)

    Park, Ye-Kyu

    2016-01-01

    Objective The management of cervical intraepithelial neoplasia (CIN) and early invasive cancer of the uterine cervix is very difficult to approach, especially in case of young woman who wants to preserve her fertility. Conization of the cervix may have various kinds of disadvantage. The objective of this clinical retrospective study is to investigate the therapeutic effects and clinical efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic therapy in patients with pre-malignant CIN and malignant invasive cervical cancer. Methods Total number of PDT trial case was 50 cases and total number of patient was 22 patients who registered to PDT clinic. We used photogem sensitizer and 632 nm diode laser in early two cases. After then we performed PDT using photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut, microlens, cylindrical diffuser, and interstitial type optic fibers in order to irradiate the lesions. 240 J/cm2 energy was irradiated to the lesions. Results CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases in the patients with invasive cervical cancer (67%). Conclusion Our data showed that CR rate was fantastic in CIN group (95%). This study suggests that PDT can be recommended as new optimistic management modality on the patients with pre-malignant CIN lesions including carcinoma in situ and relatively early invasive cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in case of invasive cervical cancer. For the young age group who desperately want to preserve their fertility and have a healthy baby, PDT can be a beacon of hope. PMID:27896250

  7. Clinical efficacy of photodynamic therapy.

    Science.gov (United States)

    Park, Ye-Kyu; Park, Choong-Hak

    2016-11-01

    The management of cervical intraepithelial neoplasia (CIN) and early invasive cancer of the uterine cervix is very difficult to approach, especially in case of young woman who wants to preserve her fertility. Conization of the cervix may have various kinds of disadvantage. The objective of this clinical retrospective study is to investigate the therapeutic effects and clinical efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic therapy in patients with pre-malignant CIN and malignant invasive cervical cancer. Total number of PDT trial case was 50 cases and total number of patient was 22 patients who registered to PDT clinic. We used photogem sensitizer and 632 nm diode laser in early two cases. After then we performed PDT using photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut, microlens, cylindrical diffuser, and interstitial type optic fibers in order to irradiate the lesions. 240 J/cm(2) energy was irradiated to the lesions. CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases in the patients with invasive cervical cancer (67%). Our data showed that CR rate was fantastic in CIN group (95%). This study suggests that PDT can be recommended as new optimistic management modality on the patients with pre-malignant CIN lesions including carcinoma in situ and relatively early invasive cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in case of invasive cervical cancer. For the young age group who desperately want to preserve their fertility and have a healthy baby, PDT can be a beacon of hope.

  8. 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.

  9. Photodynamic therapy monitoring with optical coherence angiography

    Science.gov (United States)

    Sirotkina, M. A.; Matveev, L. A.; Shirmanova, M. V.; Zaitsev, V. Y.; Buyanova, N. L.; Elagin, V. V.; Gelikonov, G. V.; Kuznetsov, S. S.; Kiseleva, E. B.; Moiseev, A. A.; Gamayunov, S. V.; Zagaynova, E. V.; Feldchtein, F. I.; Vitkin, A.; Gladkova, N. D.

    2017-01-01

    Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement. PMID:28148963

  10. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  11. Photodynamic therapy for cervical lesions

    Directory of Open Access Journals (Sweden)

    E. V. Grebenkina

    2014-01-01

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

  12. Photodynamic management of bladder cancer

    Science.gov (United States)

    Johansson, A.; Stepp, H.; Beyer, W.; Pongratz, T.; Sroka, R.; Bader, M.; Kriegmair, M.; Zaak, D.; Waidelich, R.; Karl, A.; Hofstetter, A.; Stief, C.; Baumgartner, R.

    2009-06-01

    Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.

  13. Towards Effective Photothermal/Photodynamic Treatment Using Plasmonic Gold Nanoparticles.

    Science.gov (United States)

    Bucharskaya, Alla; Maslyakova, Galina; Terentyuk, Georgy; Yakunin, Alexander; Avetisyan, Yuri; Bibikova, Olga; Tuchina, Elena; Khlebtsov, Boris; Khlebtsov, Nikolai; Tuchin, Valery

    2016-08-09

    Gold nanoparticles (AuNPs) of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT)/photodynamic (PDT) therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. In this review, we summarize our recent theoretical, experimental, and pre-clinical results on light activated interaction of AuNPs with tissues and cells. Specifically, we discuss a combined PPT/PDT treatment of tumors and killing of pathogen bacteria with gold-based nanocomposites and atomic clusters, cell optoporation, and theoretical simulations of nanoparticle-mediated laser heating of tissues and cells.

  14. Towards Effective Photothermal/Photodynamic Treatment Using Plasmonic Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Alla Bucharskaya

    2016-08-01

    Full Text Available Gold nanoparticles (AuNPs of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT/photodynamic (PDT therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. In this review, we summarize our recent theoretical, experimental, and pre-clinical results on light activated interaction of AuNPs with tissues and cells. Specifically, we discuss a combined PPT/PDT treatment of tumors and killing of pathogen bacteria with gold-based nanocomposites and atomic clusters, cell optoporation, and theoretical simulations of nanoparticle-mediated laser heating of tissues and cells.

  15. 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.

  16. Photodynamic therapy with ultrafast lasers

    Science.gov (United States)

    Wachter, Eric A.; Petersen, Mark G.; Dees, Craig

    1999-06-01

    The photodynamic properties of several photosensitive compounds have been evaluated in vivo using simultaneous two-photon excitation (TPE) and multi-photon excitation (MPE). TPE and MPE are effected using a mode-locked laser, such as the mode-locked titanium:sapphire or Nd:YLF laser, the near infrared output of which allows direct promotion of various non-resonant transitions. Such lasers are exceptionally well suited for non-linear activation of exogenous or endogenous PDT agents in biological systems due to their extremely short pulse width, modest pulse energy, and high repetition rate; these features combine to effect efficient PDT activation with minimal potential for non- specific biological damage, improved spatial localization of activation, and enhanced depth of penetration. Results in several murine models are presented.

  17. Photodynamic therapy of acne vulgaris.

    Science.gov (United States)

    Ershova, Ekaterina Y.; Karimova, Lubov N.; Kharnas, Sergey S.; Kuzmin, Sergey G.; Loschenov, Victor B.

    2003-06-01

    Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) was tested for the treatment of acne vulgaris. Patients with acne were treated with ALA plus red light. Ten percent water solution of ALA was applied with 1,5-2 h occlusion and then 18-45 J/cm2 630 nm light was given. Bacterial endogenous porphyrins fluorescence also was used for acne therapy. Treatment control and diagnostics was realized by fluorescence spectra and fluorescence image. Light sources and diagnostic systems were used: semiconductor laser (λ=630 nm, Pmax=1W), (LPhT-630-01-BIOSPEC); LED system for PDT and diagnostics with fluorescent imager (λ=635 nm, P=2W, p=50 mW/cm2), (UFPh-630-01-BIOSPEC); high sensitivity CCD video camera with narrow-band wavelength filter (central wavelength 630 nm); laser electronic spectrum analyzer for fluorescent diagnostics and photodynamic therapy monitoring (LESA-01-BIOSPEC). Protoporphyrin IX (PP IX) and endogenous porphyrins concentrations were measured by fluorescence at wavelength, correspondingly, 700 nm and 650 nm. It was shown that topical ALA is converted into PP IX in hair follicles, sebaceous glands and acne scars. The amount of resulting PP IX is sufficient for effective PDT. There was good clinical response and considerable clearance of acne lesion. ALA-PDT also had good cosmetic effect in treatment acne scars. PDT with ALA and red light assist in opening corked pores, destroying Propionibacterium acnes and decreasing sebum secretion. PDT treatment associated with several adverse effects: oedema and/or erytema for 3-5 days after PDT, epidermal exfoliation from 5th to 10th day and slight pigmentation during 1 month after PDT. ALA-PDT is effective for acne and can be used despite several side effects.

  18. 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.

  19. Is photodynamic therapy an appropriate treatment of feline superficial squamous cell carcinomas? Two case studies in small animal practice

    Science.gov (United States)

    Vinck, Elke; Cagnie, B.; Vinck, H.; Cambier, D.

    2003-12-01

    Oncological research and cancer treatment are more common in human medicine than in veterinary medicine. Nevertheless the latest decennium chemotherapy, radiotherapy and surgery also figure largely in the cancer treatment of pets. For this matter, the present study tried to explore the applicability of Photodynamic Therapy (PDT) as a proper and advantageous alternative for those treatments. PDT using topical 5-aminolaevulinic acid (5-ALA) cream was applied on superficial squamous cell carcinomas (SCC) at the nasal planum of two cats. Five hours after the cream was applied, the photosensitizing agent was removed and the sensitized area was irradiated with a red Light Emitting Diode (LED) contrivance with a wavelength of 660 nm. LED irradiation was administrated during 20 minutes, at a power output of 80 mW, with an energy density outcome of 38 J/cm2. The day after ths irradiation, the tumor area became erythematous and somewhat oedematous. After two days a scab occurred. Long-term post treatment observation showed complete removal of the malign cells related with regain of normal skin structure after three weeks. Follow-up period of one year for the first case and of two months for the second case revealed no recurrence. These promising results indicate that PDT is a possible alternative method to treat superficial skin tumors. Especially when taking into account that chemotherapy and radiotherapy are time-consuming treatments and that surgery (complete removal of the nasal planum) is not an esthetical solution.

  20. 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.

  1. Effects of balanced nutrient soluble fertilizer with 5 - ALA on the growth, flowering and nutrient content of Chinese rose%含5-氨基乙酰丙酸等养分水溶肥料对月季生长、开花及体内养分元素含量的影响

    Institute of Scientific and Technical Information of China (English)

    任忠秀; 聂立水; 张强; 孙兆地; 郝利峰

    2011-01-01

    In order to investigate the co - effects of both plant growth regulator 5 - ALA and balanced nutrient soluble fertilizer on the growth, flowering and nutrient contents of Chinese rose (Rosa hybrida), a pot experiment was conducted. Three treatments were balanced nutrient soluble fertilizer, 5 - ALA solution and balanced nutrient soluble fertilizer with 5 -ALA, while water served as a check. All treatments were applied by foliar spray. There were three replications. The results showed that the application of balanced nutrient soluble fertilizer with 5 - ALA had positive effects in promoting the growth of Chinese rose, increasing the Chinese rose flowering rate and improving the color of Chinese rose flower. Single application of 5 - ALA solution could increase chlorophyll content of per unit area of leaf by about 6. 6% , while single application of balanced nutrient soluble fertilizer could lead to significant decrease in the chlorophyll content of per unit area of leaf. Balanced nutrient soluble fertilizer was more conducive to increase nitrogen content, phosphorus content and potassium content than that of the balanced nutrient soluble fertilizer with 5 - ALA. Nitrogen content, phosphorus content and potassium content of per single plant were increased by applying the three different fertilizers, among them the balanced nutrient soluble fertilizer with S - ALA had the best yield improving effect with total primary nutrient increased by 43. 5%.%选用月季盆栽试验,以等养分水溶肥料、5-氨基乙酰丙酸盐溶液和含5-氨基乙酰丙酸等养分水溶肥料为试验材料,用清水做对照,研究了三者对月季生长、开花及植株体内养分含量的影响.结果表明,含5-氨基乙酰丙酸等养分水溶肥料更有利于月季花、茎、叶的生长,有利于促进月季开花率的增加和花色的改善;5-氨基乙酰丙酸有利于单位叶面积叶绿素含量的增加,叶绿素总量增加6.6%,而等养分水溶肥料使单位

  2. The combination treatment using CO₂ laser and photodynamic therapy for HIV seropositive men with intraanal warts.

    Science.gov (United States)

    Xu, Juan; Xiang, Li; Chen, Jiayuan; He, Qin; Li, Qing; Li, Jing; Wang, Jing

    2013-05-01

    We evaluate the effectiveness of combination treatment using photodynamic therapy after carbon dioxide laser in preventing the recurrence of condylomata acuminata for intraanal warts in HIV positive homosexual men. A retrospective survey of 41 patients referred to the STD clinic of the Fourth People's Hospital of Shenzhen for the treatment of intraanal warts among HIV positive homosexual men between Janurary 2009 and September 2011. The patients who accepted CO₂ laser monotherapy for the same diagnosis were used as the comparison group. After the confirmation of the diagnosis of HIV infection and intraanal warts, the patients were treated with the combination treatment using PDT with 5-ALA thermal gel immediately after CO₂ laser ablation of the warts. PDT was performed with irradiation of 100 J/cm² at an irradiance of 100-150 mW/cm² with a semiconductor laser, wavelength 635 nm. PDT therapy was repeated twice with 2 weekly intervals. Follow up examinations including an anoscopy every 4 weeks after the latest PDT. After 3 cycles of PDT treatments, 39 cases of anoscopy examination showed no new or recurrent lesions. At the end of the sixth months, recurrence occurred in 12(29%) cases. HPV 11 was present in 6 (50%) of these recurrences. HPV 6/11 or 16/18 remains positive in 19 cases (46.3%) and HPV negative in 22 cases. The combination treatment with CO₂ laser and PDT is much more effective in reducing the treatment cycles and the time intervals of the whole treatment for intraanal warts in HIV infected people. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Photodynamic therapy in the treatment of epithelial potentially malignant disorders of the mouth: advantages and disadvantages

    Science.gov (United States)

    Gaimari, G.; Russo, C.; Palaia, G.; Tenore, G.; Del Vecchio, A.; Romeo, U.

    2016-03-01

    Introduction: Leukoplakia is a potentially malignant epithelial lesion with carcinomatous percentages transformation comprehended between 1% and 7% for the homogeneous forms and from 4% to 15% for the non-homogeneous ones. Their removal can be performed by scalpel or laser surgery (excision or vaporization). Photodynamic therapy (PDT) is a bloodless treatment option, based on the involvement of three elements: light, photosensitizer and oxygen. When the molecules of the photosensitizer are activated by a low power laser, energy is transferred to molecular oxygen creating highly reactive radicals of oxygen, that have a cytotoxic effect on target cells. Aim of the study: According to several studies in Literature, it has been decided to evaluate through an initial clinical trial, the efficacy of PDT using topical aminolevulinic acid (5-ALA) activated by a laser diode (λ = 635 nm) to treat potentially oral malignant lesions and to illustrate the advantages and disadvantages derived from the use of this technique. Materials and Methods: Five patients, affected by oral leukoplakia (OL) and oral verrucous leukoplakia (OVL) on the mucosal cheeks, labial commissure, fornix and retromolar areas, have been treated using the PDT. Irradiation time with Diode laser: 1000s. Irradiation mode: Scanning. 5 cycles of 3 minute + final cycle of 100 seconds. Each cycle has been interrupted by pauses of 3 minutes. Results and conclusion: PDT results to be effective in the treatment of OL, especially on OVL. In fact, OVL, due to its irregularity, has got an area of increased retention for the gel that is more difficult to be removed by salivary flow. This could explain the better results obtained in this case rather than in those ones of OL. Furthermore, the advantages have been represented by: less invasivity, high sensitivity for altered tissues, minimal scar tissue, less side effects and no pain during and after operation. In contrast to this, the disadvantages were: longer treatment

  4. 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.

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

    Science.gov (United States)

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

    2017-09-01

    In order to improve the efficacy of photodynamic therapy (PDT), biotin was axially conjugated with silicon(IV) phthalocyanine (SiPc) skeleton to develop a new tumor-targeting photosensitizer SiPc-biotin. The target compound SiPc-biotin showed much higher binding affinity toward BR-positive (biotin receptor overexpressed) HeLa human cervical carcinoma cells than its precursor SiPc-pip. However, when the biotin receptors of HeLa cells were blocked by free biotin, >50% uptake of SiPc-biotin was suppressed, demonstrating that SiPc-biotin could selectively accumulate in BR-positive cancer cells via the BR-mediated internalization. The confocal fluorescence images further confirmed the target binding ability of SiPc-biotin. As a consequence of specificity of SiPc-biotin toward BR-positive HeLa cells, the photodynamic effect was also largely dependent on the BR expression level of HeLa cells. The photodynamic activities of SiPc-biotin against HeLa cells were dramatically reduced when the biotin receptors were blocked by the free biotin (IC50: 0.18μM vs. 0.46μM). It is concluded that SiPc-biotin can selectively damage BR-positive cancer cells under irradiation. Furthermore, the dark toxicity of SiPc-biotin toward human normal liver cell lines LO2 was much lower than that of its precursor SiPc-pip. The targeting photodynamic activity and low dark toxicity suggest that SiPc-biotin is a promising photosensitizer for tumor-targeting photodynamic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Does photodynamic therapy enhance standard antibacterial therapy in dentistry?

    Science.gov (United States)

    Javed, Fawad; Romanos, Georgios E

    2013-11-01

    The aim of this study was to assess whether or not photodynamic therapy enhanced standard antibacterial therapy in dentistry. Photodynamic therapy when used as an adjunct to conventional periodontal therapy kills more bacteria than when conventional periodontal therapy is used alone. To address the focused question, "Does photodynamic therapy enhance killing of oral bacteria?" PubMed/MEDLINE(®) and Google Scholar databases were explored. Original human and experimental studies and studies using photodynamic therapy for killing oral bacteria were included. Letters to the Editor, historic reviews, and unpublished data were excluded. Photodynamic therapy significantly reduces periodontopathogenic bacteria including Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis. Photodynamic therapy kills cariogenic bacteria (such as Streptococcus mutans and Streptococcus sanguis), bacteria associated with infected root canals, and those associated with periimplantitis. Photodynamic therapy, when used as an adjunct to conventional oral disinfection protocols, enhances standard antibacterial therapy in dentistry.

  7. Photodynamic inactivation of mammalian viruses and bacteriophages.

    Science.gov (United States)

    Costa, Liliana; Faustino, Maria Amparo F; Neves, Maria Graça P M S; Cunha, Angela; Almeida, Adelaide

    2012-07-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  8. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  9. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Science.gov (United States)

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  10. 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser therapy in treatment of condyloma acuminatum%5-氨基酮戊酸光动力疗法联合二氧化碳激光治疗尖锐湿疣的疗效观察

    Institute of Scientific and Technical Information of China (English)

    顾俊瑛; 史玉玲; 李秀丽; 李晓建; 刘至昱; 高飞

    2011-01-01

    目的 比较5-氨基酮戊酸光动力疗法(5-aminolevulinic acid-mediated photodynamic therapy,ALA-PDT)和二氧化碳( CO2)激光治疗尖锐湿疣(CA)的临床疗效.方法 将同济大学附属第十人民医院皮肤科2010年4月至2010年12月就治的111例尖锐湿疣患者分为3组,第一组为特殊部位(尿道口、系带或宫颈部位)的疣体患者,共17例,单用ALA-PDT治疗;余94例患者随机分为两组,每组47例,分别采用ALA-PDT联合CO2激光治疗和单一CO2激光治疗.ALA-PDT每周治疗1次,3次为1个疗程.CO2激光治疗根据疣体大小一次或分次清除疣体.3组患者治疗结束后每1、2、3个月分别电话随访一次.结果 单用ALA-PDT组一个疗程结束后的清除率为93.4%(16/17),3个月后总复发率为11.8%(2/17).联合治疗组和CO2激光单一治疗组3个月后的总复发率分别为14.9%(7/47)和55.3%(26/47),差异有统计学意义(x2=16.857,P<0.001).结论 ALA-PDT联合CO2激光治疗CA疗效确切,复发率低;ALA-PDT可有效治疗特殊部位的疣体,临床适用范围广.%Objective To evaluate the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) combined with CO2 laser therapy in treatment of condyloma acuminatum. Methods One hundred and eleven patients with condyloma acuminatum admitted from April to December 2010 were enrolled in the study. Seventeen cases whose condylomas are at urethral orifice, vinculum or cervix uteri were treated with ALA-PDT alone. Other 94 cases were randomly assigned into two groups with 47 in each, who were treated by ALA-PDT combined with CO2 laser therapy or CO2 laser alone, respectively. Results The clearance rate was 93. 4% (16/17) and the relapse rate was 11.8% (2/17) in patients treated with ALA-PDT alone. The relapse rates of ALA-PDT combined with CO2 laser and CO2 laser alone were 14. 9% (7/47 ) and 55. 3% (26/47 ) , respectively (x2 = 16. 857, P < 0. 001). Conclusion ALA-PDT is effective in treatment of condyloma

  11. 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.

  12. Photodynamic therapy of cancer — Challenges of multidrug resistance

    Directory of Open Access Journals (Sweden)

    Zheng Huang

    2015-01-01

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

  13. Porphyrins for photodynamic therapy of cancer

    Science.gov (United States)

    Ion, Rodica-Mariana; Pascu, Mihail-Lucian

    2001-06-01

    Photodynamic therapy (PDT) of cancer is based on the dye- sensitized photooxidation of different biological targets in the tumoral tissue yielding to a photochemically induced cell's death. The effectiveness of this treatment method depends on the photophysical and photochemical properties of the used photosensitizer-drug during the irradiation with visible light (laser beam) and/or the ionizing radiation. The purpose of this paper is to summarize the photodynamic therapy applications: substitution effects, ionization and aggregation processes effects, photodegradation reaction implications, the correlation with some medical applications on human brain cells.

  14. Photodynamic therapy to treat periimplantitis.

    Science.gov (United States)

    Bombeccari, Gian Paolo; Guzzi, Gianpaolo; Gualini, Federico; Gualini, Sara; Santoro, Franco; Spadari, Francesco

    2013-12-01

    : Periimplantitis is a bacterial complication after dental implants implantation. Photodynamic therapy (PDT) implies the use of low-power laser in combination with appropriate photosensitizer to increase the detoxification of the implant surfaces. Little information exists about PDT in the treatment of periimplantitis. A randomized comparative case-control study has been conducted with 20 patients and 20 controls to compare the efficacy of antimicrobial PDT versus surgical therapy in patients with periimplantitis, who have received dental implants with rough surfaces. In the surgery group, mucoperiosteal flap surgery was used with scaling on implant surfaces and debridement of granulation tissue. Microbiologic testing was evaluated before and after intervention treatment, at 12 and 24 weeks in the study subjects. Total anaerobic counts of bacteria did not differ significantly between patients assigned to receive PDT and those assigned to receive surgical therapy (mean, 95.2% and 80.85%, respectively). PDT was associated with a significant decrease in bleeding scores (P = 0.02) as well as inflammatory exudation (P = 0.001). Treatment with PDT in patients with periimplantitis was not associated with major reduction of total anaerobic bacteria on the rough surfaces of dental implants as compared with surgical therapy. A significantly lower proinflammatory index of periimplantitis was observed in the PDT group at 24 weeks of follow-up.

  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. Photodynamic therapy - A strategic review

    Directory of Open Access Journals (Sweden)

    Malik Rajvir

    2010-01-01

    Full Text Available Mechanical removal of the biofilm and adjunctive use of antibacterial disinfectants or various antibiotics have been conventional methods of the periodontitis therapy. There has been an upsurge of bacterial strains becoming resistant due to the injudicious use of antibiotics, recently. As a result there is pronounced interest and keenness in the development of alternate antimicrobial concepts. As the scientific community seeks alternatives to antibiotic treatment, periodontal researchers have found that photodynamic therapy (PDT is advantageous to suppress anaerobic bacteria. Hence, PDT could be an alternative to conventional periodontal therapeutic methods. This review elucidates the evolution and use of photo dynamic therapy. The application of photosensitizing dyes and their excitation by visible light enables effective killing of periodontopathogens. Even though PDT is still in the experimental stages of development and testing, the method may be an adjunct to conventional antibacterial measures in periodontology. PDT application has an adjunctive benefit besides mechanical treatment at sites with difficult access. Necessity for flap operations may be reduced, patient comfort may increase and treatment time decrease. Clinical follow-up studies are needed to confirm the efficacy of the procedure.

  17. New photosensitizers for photodynamic therapy

    Science.gov (United States)

    Abrahamse, Heidi; Hamblin, Michael R.

    2016-01-01

    Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. PMID:26862179

  18. Photodynamic therapy of gastric cancer

    Science.gov (United States)

    Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

    1996-01-01

    Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

  19. Fluorescence endoscopy and photodynamic therapy.

    Science.gov (United States)

    Messmann, H; Endlicher, E; Gelbmann, C M; Schölmerich, J

    2002-10-01

    Fluorescence endoscopy is a new technique which allows a better detection of non-visible malignant or premalignant lesions or, those which are difficult to detect. Exogenously applied sensitisers accumulate selectively in malignant lesions and induce fluorescence after illumination with light of adequate wavelength. However, also endogenous fluorophores, different located in malignant or benign lesions, induce a different autofluorescence in these lesions. Tissue fluorescence can be detected by optical sampling of the mucosa using fluorescence spectroscopy or by generating real time fluorescence images with specialised camera systems. Compared to point fluorescence spectroscopy the latter technique enables the screening of large surface areas of mucosa. Meanwhile, fluorescence endoscopy is a widely used technique in urology employing 5-aminolaevulinic acid sensitisation. In gastroenterology, this technique seems promising for the detection of early cancers or dysplasia in patients with Barrett's oesophagus or ulcerative colitis. Using different sensitisers, photodynamic therapy seems to be a promising option for patients with advanced oesophageal cancer and in the palliative treatment of non-resectable bile duct cancer, furthermore for patients with early gastric cancer and dysplasia in Barrett's oesophagus. Probably, by laser light fractionation or a combination of different sensitisers, an enhanced effect can be expected.

  20. TUMOR-SPECIFIC IMMUNE RESPONSE AFTER PHOTODYNAMIC THERAPY

    Directory of Open Access Journals (Sweden)

    Yu. N. Anokhin

    2016-01-01

    Full Text Available Increased incidence of malignancies requires a search for new therapeutic approaches. E.g., photodynamic therapy (PDT is an effective anti-cancer treatment that involves administration of a photosensitizing dye followed by visible light irradiation of the tumor. Pre-clinical studies have shown that local photodynamic therapy enhances systemic antitumor immunity. Moreover, it is well known that the long-term effects of PDT depend on functioning of intact adaptive immune response. In this context, the immune system plays a fundamental role. Interestingly, the PDT action is associated with stimulation of systemic immune response against a locally treated tumor. In fact, PDT has been shown to effectively stimulate both innate and adaptive immune systems of the host, by triggering the release of various pro-inflammatory and acutephase response mediators thus leading to massive infiltration of the treated site with neutrophils, dendritic cells and other inflammatory cells. PDT efficacy depends, in part, on induction of tumor-specific immune response which is dependent on cytotoxic T lymphocytes and natural killer (NK cells. The set of specific receptors enables NK cells to recognize surface molecules on the target cells. Expression of the latter molecules is indicative of viral infection, tumor formation, or cell stress (e.g., DNA damage. The NK cells are also involved into various biological processes in the organism, playing a critical role in immune surveillance, thus representing a potential tool for cancer therapy. It was shown that the tumor cells have increased sensitivity to NK cell-mediated lytic action following PDT. In this review, we further discuss potential relationships between PDT and antitumor immune response.

  1. 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.

  2. 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

  3. 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,...

  4. [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...

  5. Enhancing photodynamic therapy of refractory solid cancers

    NARCIS (Netherlands)

    Weijer, R.

    2017-01-01

    Photodynamic therapy (PDT) is based on the activation of a photosensitizer by (laser) light to locally produce highly destructive reactive oxygen species. When employed for cancer treatment, PDT is able to induce tumor cell death, microvascular damage, and an anti-tumor immune response. All these

  6. 甲苯胺蓝介导的光动力疗法对大鼠口腔牙周致病菌灭菌效果的研究%Study of the Effect of Toluidine Blue- Mediated Photodynamic Therapy of Periodontal Bacteria from Subgingival Plaques in Rats

    Institute of Scientific and Technical Information of China (English)

    栾秀玲; 秦艳利; 胡艳秋

    2012-01-01

    to host tissues. PLI was from 3 to 1 and SBI was from 4 to 1. Conclusion: Toluidine blue-mediated photodynamic therapy could effectively treat periodontitis in rats and has high potential in clinical application.

  7. An effective zinc phthalocyanine derivative for photodynamic antimicrobial chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-01

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

  8. [Photodynamic therapy for gastric cancer].

    Science.gov (United States)

    Mimura, S; Narahara, H; Uehara, H; Otani, T; Okuda, S

    1996-01-01

    the efficacy of ADL and EDL, the relation between the response (cure or no cure) and irradiated energy intensity (dose: J/cm 2) was evaluated by the depth of cancer invasion and kind of laser used in PDT. A smaller EDL dose was more effective than ADL in terms of photodynamic action.

  9. Photodynamic therapy for recurrent respiratory papillomatosis.

    Science.gov (United States)

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

    2014-06-05

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

  10. Photodynamic injury of isolated crayfish neuron and surrounding glial cells: the role of p53

    Science.gov (United States)

    Sharifulina, S. A.; Uzdensky, A. B.

    2015-03-01

    The pro-apoptotic transcription factor p53 is involved in cell responses to injurious impacts. Using its inhibitor pifithrin- α and activators tenovin-1, RITA and WR-1065, we studied its potential participation in inactivation and death of isolated crayfish mechanoreceptor neuron and satellite glial cells induced by photodynamic treatment, a strong inducer of oxidative stress. In dark, p53 activation by tenovin-1 or WR-1065 shortened activity of isolated neurons. Tenovin-1 and WR-1065 induced apoptosis of glial cells, whereas pifithrin-α was anti-apoptotic. Therefore, p53 mediated glial apoptosis and suppression of neuronal activity after axotomy. Tenovin-1 but not other p53 modulators induced necrosis of axotomized neurons and surrounding glia, possibly, through p53-independent pathway. Under photodynamic treatment, p53 activators tenovin-1 and RITA enhanced glial apoptosis indicating the pro-apoptotic activity of p53. Photoinduced necrosis of neurons and glia was suppressed by tenovin-1 and, paradoxically, by pifithrin-α. Modulation of photoinduced changes in the neuronal activity and necrosis of neurons and glia was possibly p53-independent. The different effects of p53 modulators on neuronal and glial responses to axotomy and photodynamic impact were apparently associated with different signaling pathways in neurons and glial cells.

  11. p53 family members - important messengers in cell death signaling in photodynamic therapy of cancer?

    Science.gov (United States)

    Acedo, Pilar; Zawacka-Pankau, Joanna

    2015-08-01

    TP53 is one of the genes most frequently inactivated in cancers. Mutations in TP53 gene are linked to worse prognosis and shorter overall survival of cancer patients. TP53 encodes a critical tumor suppressor, which dictates cell fate decisions upon stress stimuli. As a sensor of cellular stress, p53 is a relevant messenger of cell death signaling in ROS-driven photodynamic therapy (PDT) of cancer. The significant role of p53 in response to PDT has been reported for several clinically approved photosensitizers. Multiple reports described that wild-type p53 contributes to cell killing upon photodynamic therapy with clinically approved photosensitizers but the mechanism is still not fully understood. This work outlines the diverse functions of p53 family members in cancer cells' susceptibility and resistance to PDT. In summary p53 and p53 family members are emerging as important mediators of cell death signaling in photodynamic therapy of cancer, however the mechanism of cell death provoked during PDT might differ depending on the tissue type and the photosensitizer applied.

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

    Science.gov (United States)

    Lamberti, María Julia; Vittar, Natalia Belén Rumie; Rivarola, Viviana Alicia

    2014-12-10

    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 will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to target tumors. Selective therapies can be established by focusing on distinctive intracellular (receptors, apoptotic pathways, multidrug resistance system, nitric oxide-mediated stress) and environmental (glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity.

  13. Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for magnetically amplified photothermal and photodynamic cancer therapy.

    Science.gov (United States)

    Bhana, Saheel; Lin, Gan; Wang, Lijia; Starring, Hunter; Mishra, Sanjay R; Liu, Gang; Huang, Xiaohua

    2015-06-03

    We present the synthesis and application of a new type of dual magnetic and plasmonic nanostructures for magnetic-field-guided drug delivery and combined photothermal and photodynamic cancer therapy. Near-infrared-absorbing gold nanopopcorns containing a self-assembled iron oxide cluster core were prepared via a seed-mediated growth method. The hybrid nanostructures are superparamagnetic and show great photothermal conversion efficiency (η=61%) under near-infrared irradiation. Compact and stable nanocomplexes for photothermal-photodynamic therapy were formed by coating the nanoparticles with near-infrared-absorbing photosensitizer silicon 2,3-naphthalocyannie dihydroxide and stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. The nanocomplex showed enhanced release and cellular uptake of the photosensitizer with the use of a gradient magnetic field. In vitro studies using two different cell lines showed that the dual mode photothermal and photodynamic therapy with the assistance of magnetic-field-guided drug delivery dramatically improved the therapeutic efficacy of cancer cells as compared to the combination treatment without using a magnetic field and the two treatments alone. The "three-in-one" nanocomplex has the potential to carry therapeutic agents deep into a tumor through magnetic manipulation and to completely eradicate tumors by subsequent photothermal and photodynamic therapies without systemic toxicity.

  14. Cyanines as efficient photosensitizers in photodynamic reaction: photophysical properties and in vitro photodynamic activity.

    Science.gov (United States)

    Kulbacka, J; Pola, A; Mosiadz, D; Choromanska, A; Nowak, P; Kotulska, M; Majkowski, M; Hryniewicz-Jankowska, A; Purzyc, L; Saczko, J

    2011-04-01

    The purpose of the present study was to explore the potential application of cyanines in photodynamic treatment. The photophysical features of four cyanines (KF570, HM118, FBF-749, and ER-139) were investigated by elemental and spectral analyses. Two malignant cell lines (MCF-7/WT and MCF-7/DOX) were used to test the potential for use in the photodynamic therapy. The cytotoxic effects of these dyes were determined by the MTT assay after 4 and 24 h of incubation with the cyanine. KF570 and HM118 were irradiated with red light (630-nm filter) and FBF-749 and ER-139 with green light (435-nm filter). The results showed that the cyanine HM118 demonstrated a major phototoxic effect. It was also noted that the efficiency of photodynamic therapy was higher in the doxorubicin-resistant cell line (MCF-7/DOX).

  15. Photodynamic therapy of cervical intraepithelial neoplasia

    Science.gov (United States)

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

    2014-03-01

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

  16. Second generation photodynamic agents: a review.

    Science.gov (United States)

    Sternberg, E D; Dolphin, D

    1993-10-01

    Over the last decade, laser treatment of neoplastic diseases has become routine. The ability of these light-induced therapies to effect positive results is increased with the utilization of photosensitizing dyes. The approval of Photofrin in Canada as a first generation photodynamic therapeutic agent for the treatment of some forms of bladder cancer is being followed by the development of other agents with improved properties. At this time a number of second generation photosensitizing dyes are under study in phase I/II clinical trials. A review of the status of these trials along with mechanistic aspects is reviewed in this article. In addition, a review of the status of lasers to be utilized for photodynamic therapy gives some indication of which instruments could be considered for this therapy in the future.

  17. Present status of photodynamic procedures in urology

    Science.gov (United States)

    Jocham, Dieter; Thomas, Stephen

    1994-03-01

    Since 1976, photodynamic therapy (PDT) has been used for the treatment of different stages of urothelial bladder tumors. First applications were based on the irradiation of single exophytic tumors using bare fibers for laser irradiation (630 mm) or bright white light generated e.g. from a mercury arc lamp. Clinical results of several centers demonstrated the possibility of destroying single superficially growing tumors. A new approach to the treatment of multifocal growing tumors, including the endoscopically often undetectable carcinoma in situ, was provided by the development of treatment modalities allowing for whole bladder wall irradiation. Photodynamic diagnosis (PDD) is a novel procedure for detecting flat precancerous and malignant lesions undetectable by endoscopy alone on the basis of laser- induced fluorescence.

  18. 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.

  19. INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR METASTATIC PERITONEAL TUMORS

    Directory of Open Access Journals (Sweden)

    E. A. Suleimanov

    2016-01-01

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

  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. δ氨基酮戊酸光动力疗法对体外培养三株嗜角质真菌杀伤效应的实验研究%Antifungal Effect of Delta-Aminolevulinic Acid Mediated Photodynamic Therapy on Three Strains of Kratinophilic Fungi in Vitro

    Institute of Scientific and Technical Information of China (English)

    黄望强; 史赢; 雷铁池

    2012-01-01

    Objective: To evaluate the killing effect of S-Aminolevulinic acid (ALA) -mediated photody-namic therapy on three strains of keratinophilic fungi in vitro and to investigate its mechanism. Methods: Trichophyton rubrum , Trichophyton mentagrophytes, and Candida albicans were inoculated in Sabouraud glucose peptone, for preparing fungi suspensions. The fungi suspensions were treated with different concentrations of ALA (3, 10, 30, 100, and 300 mmol/L) cultures in DMEM containing 2. 5% fetal calf serum. Confocal fluorescence microscope was used to examine proto-porphyrin IX (PpIX) formation. MTT assay was used to determine the inhibitory rates by different concentrations of ALA-PDT. The ult restructure changes of fungi were observed by transmission electron microscopy after the treatment of 100 mmol/L ALA-PDT. Results: After incubated with 100 mmol/L ALA, PpK was shown as brick-red fluorescent signal in the three stains of fungal inside by confocal laser scanning microscope. There is a positive correlation be-tween the concentration of ALA and the inhibition ratio of three strains of fungi (P<0. 05), but when the concentration of ALA increased to 300 mmol/L, the inhibition rate did not increase significantly. Simple laser and simple ALA treatment had no significant inhibition on fungal growth. The structures of cell wall, cell membrane, and organelles in all the three strains of fungi were destroyed at some extent after 100 mmol/L ALA-PDT treatment. Conclusion: 8-Aminolevulini-cacid-mediated photodynamic treatment have a definite killing effect in these, three strains fungi in vitro, which provides a theoretical basis for treatment of onychomycosis.%目的:探讨δ氨基酮戊酸(ALA)光动力学疗法(PDT)对体外培养的三株嗜角质真菌杀伤效应及作用机制.方法:将红色毛癣菌、须癣毛癣菌、白念珠菌三株标准菌株在沙氏葡萄糖琼脂培养基(SDA)活化培养后制备菌悬液,菌悬液与不同浓度ALA(3,10,30,100,300mmol

  2. Pulse mode of laser photodynamic treatment induced cell apoptosis.

    Science.gov (United States)

    Klimenko, Vladimir V; Knyazev, Nickolay A; Moiseenko, Fedor V; Rusanov, Anatoliy A; Bogdanov, Alexey A; Dubina, Michael V

    2016-03-01

    One of the factors limiting photodynamic therapy (PDT) is hypoxia in tumor cells during photodynamic action. PDT with pulse mode irradiation and appropriate irradiation parameters could be more effective in the singlet oxygen generation and tissue re-oxygenation than continuous wave (CW) mode. We theoretically demonstrate differences between the cumulative singlet oxygen concentration in PDT using pulse mode and CW mode of laser irradiation. In vitro experimental results show that photodynamic treatment with pulse mode irradiation has similar cytotoxicity to CW mode and induces mainly cell apoptosis, whereas CW mode induces necrotic cell death. We assume that the cumulative singlet oxygen concentration and the temporal distribution of singlet oxygen are important in photodynamic cytotoxicity and apoptosis initiation. We expect our research may improve irradiation protocols and photodynamic therapy efficiency.

  3. Graphene-based nanovehicles for photodynamic medical therapy.

    Science.gov (United States)

    Li, Yan; Dong, Haiqing; Li, Yongyong; Shi, Donglu

    2015-01-01

    Graphene and its derivatives such as graphene oxide (GO) have been widely explored as promising drug delivery vehicles for improved cancer treatment. In this review, we focus on their applications in photodynamic therapy. The large specific surface area of GO facilitates efficient loading of the photosensitizers and biological molecules via various surface functional groups. By incorporation of targeting ligands or activatable agents responsive to specific biological stimulations, smart nanovehicles are established, enabling tumor-triggering release or tumor-selective accumulation of photosensitizer for effective therapy with minimum side effects. Graphene-based nanosystems have been shown to improve the stability, bioavailability, and photodynamic efficiency of organic photosensitizer molecules. They have also been shown to behave as electron sinks for enhanced visible-light photodynamic activities. Owing to its intrinsic near infrared absorption properties, GO can be designed to combine both photodynamic and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues and future aspects of photodynamic therapy research are addressed in this review.

  4. Topical 5-aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa

    Directory of Open Access Journals (Sweden)

    Linglin Zhang

    2016-01-01

    Full Text Available Acne conglobata (AC, perifolliculitis capitis abscedens et suffodiens (PCAS and hidradenitis suppurativa (HS are uncommon refractory chronic, inflammatory, scarring diseases but cause serious damage to the quality of life. These three diseases are associated with follicular occlusion. Several studies indicated topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT improved follicular occlusion besides acne treatment. So we attempted to apply ALA-PDT to medicine resistant AC, PCAS and HS. Topical ALA-PDT was applied to 10 patients with AC, seven patients with PCAS and three patients with HS for more than three sessions. All the patients completed the dermatology life quality index (DLQI questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment. Adverse effects were recorded at each visit. The results showed 25.5% (5/20, two cases of AC and three cases of PCAS of patients achieved excellent improvement after three sessions of PDT and another 60.0% (12/20, eight cases of AC and four cases of PCAS of patients achieved good improvement. 15.0% (3/20, three cases of HS got poor response (< 20% lesions clearance. Another five cases (three cases of AC and two cases of PCAS also achieved excellent response after 5–7 sessions of PDT. We also found that papular/nodular, cyst/abscess showed higher clearance rate than sinus/fistula (88.5%, 86.1% versus 11.1%. DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients. 5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS. The efficacy increased with more treatment sessions.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Daylight-mediated photodynamic therapy (PDT) is a simple and tolerable treatment of nonmelanoma skin cancer. It is of interest which light intensity is sufficient to prevent accumulation of protoporphyrin IX (PpIX) and effectively treat actinic keratoses (AKs). We compared the efficacy of PDT...... with light-emitting diode (LED) to daylight-mediated PDT with very low-intensity artificial daylight ('daylight') in the treatment of multiple AKs in the face or scalp....

  6. 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.

  7. Photodynamic dosimetry in the treatment of periodontitis

    Science.gov (United States)

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

    2009-06-01

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

  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 skin field cancerization

    DEFF Research Database (Denmark)

    Braathen, L R; Morton, C A; Basset-Seguin, N

    2012-01-01

    in this area. With respect to the skin, this term is used to define the presence of multiple non-melanoma skin cancer, its precursors, actinic keratoses and dysplastic keratinocytes in sun exposed areas. The multiplicity of the lesions and the extent of the area influence the treatment decision. Providing...... at least equivalent efficacy and tolerability, field directed therapies are therefore often more worthwhile than lesion targeted approaches. Photodynamic therapy (PDT) with its selective sensitization and destruction of diseased tissue is one ideal form of therapy for this indication. In the following...... paper the use of PDT for the treatment of field cancerized skin is reviewed and recommendations are given for its use....

  10. Semiconductor quantum dots for photodynamic therapy.

    Science.gov (United States)

    Samia, Anna C S; Chen, Xiaobo; Burda, Clemens

    2003-12-24

    The applicability of semiconductor QDs in photodynamic therapy (PDT) was evaluated by studying the interaction between CdSe QDs with a known silicon phthalocyanine PDT photosensitizer, Pc4. The study revealed that the QDs could be used to sensitize the PDT agent through a fluorescence resonance energy transfer (FRET) mechanism, or interact directly with molecular oxygen via a triplet energy-transfer process (TET). Both mechanisms result in the generation of reactive singlet oxygen species that can be used for PDT cancer therapy.

  11. Progress of Photodynamic Therapy in Gastric Cancer

    OpenAIRE

    Seishiro Mimura; Hiroyuki Narahara; Toru Otani; Shigeru Okuda

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm2 for an argon dye laser and 60 J/cm2 for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm2 in...

  12. 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.

  13. 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.

  14. Photodynamic Therapy and Non-Melanoma Skin Cancer

    Science.gov (United States)

    Griffin, Liezel L.; Lear, John T.

    2016-01-01

    Non-melanoma skin cancer (NMSC) is the most common malignancy among the Caucasian population. Photodynamic therapy (PDT) is gaining popularity for the treatment of basal cell carcinoma (BCC), Bowen’s disease (BD) and actinic keratosis (AK). A topical or systemic exogenous photosensitiser, results in selective uptake by malignant cells. Protoporphyrin IX (PpIX) is produced then activated by the introduction of a light source. Daylight-mediated MAL (methyl aminolaevulinate) PDT for AKs has the advantage of decreased pain and better patient tolerance. PDT is an effective treatment for superficial BCC, BD and both individual and field treatment of AKs. Excellent cosmesis can be achieved with high patient satisfaction. Variable results have been reported for nodular BCC, with improved outcomes following pretreatment and repeated PDT cycles. The more aggressive basisquamous, morphoeic infiltrating subtypes of BCC and invasive squamous cell carcinoma (SCC) are not suitable for PDT. Prevention of “field cancerization” in organ transplant recipients on long-term immunosuppression and patients with Gorlin syndrome (naevoid basal cell carcinoma syndrome) is a promising development. The optimisation of PDT techniques with improved photosensitiser delivery to target tissues, new generation photosensitisers and novel light sources may expand the future role of PDT in NMSC management. PMID:27782094

  15. Photodynamic Therapy and Non-Melanoma Skin Cancer

    Directory of Open Access Journals (Sweden)

    Liezel L. Griffin

    2016-10-01

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

  16. Strategies to potentiate immune response after photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Hamblin, Michael R.

    2017-02-01

    Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not yet advanced to a mainstream cancer treatment. Although PDT has been shown to be an efficient photochemical way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT a great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. Some of these combination approaches use immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen associated molecular patterns. Other approaches use cytokines and growth factors whether directly administered or genetically encoded. A promising approach targets regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised.

  17. Advances in antimicrobial photodynamic inactivation at the nanoscale

    Science.gov (United States)

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

    2017-08-01

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

  18. Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis

    Science.gov (United States)

    Fateye, B.; He, C.; Chen, B.

    2009-06-01

    Vascular targeting photodynamic therapy (vPDT) is currently in clinical trial for prostate cancer (PCa) treatment. In order to study the effect of vPDT on tumor metastasis, GFP-PC3 or PC-3 xenografts were treated with verteporfin (BPD) PDT. Vascular function was assessed by ultrasound imaging; lymph node and lung metastasis were assessed by fluorescence imaging. vPDT significantly reduced tumor blood flow within 30minutes to 2 hours of treatment. Sub-curative treatment resulted in re-perfusion within 2 weeks of treatment and increased lymph node metastasis. With curative doses, no metastasis was observed. In order to identify cellular or matrix factors and cytokines implicated, conditioned medium from BPD PDTtreated endothelial cells was incubated with PC3 cells in vitro. Tumor cell proliferation and migration was assessed. By immunoblotting, we evaluated the change in mediators of intracellular signaling or that may determine changes in tumor phenotype. Low sub-curative dose (200ng/ml BPD) of endothelial cells was associated with ~15% greater migration in PC3 cells when compared with control. This dose was also associated with sustained activation of Akt at Ser 473, an upstream effector in the Akt/ mTOR pathway that has been correlated with Gleason scores in PCa and with survival and metastasis in vitro and in vivo. In conclusion, the study implicates efficacy of PDT of endothelial cells as an important determinant of its consequences on adjacent tumor proliferation and metastasis.

  19. Photodynamic Action of Single-Walled Carbon Nanotubes.

    Science.gov (United States)

    Murakami, Tatsuya

    2017-01-01

    Photodynamic therapy is achieved by the combination of photosensitizers, harmless visible or near-infrared (NIR) light, and molecular oxygen (O2). Photosensitizers transfer their absorbed light energy to O2 to generate a major active species in photodynamic therapy, singlet oxygen. In this review, I will discuss the possibility of single-walled carbon nanotubes as NIR photosensitizers, while explaining the general photophysics and photochemistry underlying photodynamic therapy as well as summarizing recent advances in the purification technologies for single-walled carbon nanotubes to reduce their toxicity concerns.

  20. Clinical use of photodynamic therapy in ocular tumors.

    Science.gov (United States)

    Cerman, Eren; Çekiç, Osman

    2015-01-01

    Although the introduction of intravitreal anti-vascular endothelial growth factor drugs reduced the indications for photodynamic therapy in ophthalmology, it may still be used in various ocular tumors. Although many studies have shown that photodynamic therapy is effective in ocular tumors, the literature consists of case reports and series. In this review, we systematically performed a meta-analysis for the use of photodynamic therapy in circumscribed choroidal hemangioma, diffuse choroidal hemangioma, retinal capillary hemangioma, von Hippel-Lindau angiomatosis, choroidal melanoma, retinal astrocytoma, retinoblastoma, eyelid tumors, conjunctival tumors, and choroidal metastasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy.

    Science.gov (United States)

    Kuo, Wen-Shuo; Chang, Yi-Ting; Cho, Keng-Chi; Chiu, Kuo-Chih; Lien, Chi-Hsiang; Yeh, Chen-Sheng; Chen, Shean-Jen

    2012-04-01

    Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) and gold nanoparticles (Au NPs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs and Au NPs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs and Au NPs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Moreover, the photochemical destruction ability would have a gradually increase depending on different sizes of Au NPs. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PTT and PDT proved to be efficiently killing cancer cells as compared to PTT or PDT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability. As a result, the preparation of Au-based nanomaterials conjugated with ICG as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

  2. Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.

    Science.gov (United States)

    Butzbach, Kathrin; Rasse-Suriani, Federico A O; Gonzalez, M Micaela; Cabrerizo, Franco M; Epe, Bernd

    2016-07-01

    Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within albumin-β-carbolinium conjugate proved to be phototoxic, while the corresponding albumin-β-carbolinium conjugates without FA were nontoxic, both with and without irradiation. An excess of free folate as competitor for the FRα-mediated uptake completely inhibited the photocytotoxicity. Interestingly, the albumin conjugates are devoid of photodynamic activity under cell-free conditions, as shown for DNA as a target. Thus, phototoxicity requires cellular uptake and lysosomal degradation of the conjugates. In conclusion, albumin-folate conjugates appear to be promising vehicles for a tumor cell targeted PDT.

  3. The influence of 5-ALA-IPL-PDT on the secretion of MMP-1 and TGF-β1 in fibroblasts pathway mechanisms%5-氨基酮戊酸联合IPL 光动力疗法对成纤维细胞分泌MMP-1、TGF-β1的影响及信号机制研究

    Institute of Scientific and Technical Information of China (English)

    黄进华; 郭爱元; 陈静; 鲁建云; 向亚平; 左成忻; 杨盛波; 谭丽娜; 康健

    2011-01-01

    目的:研究观察5-氨基酮戊酸(5-ALA)联合强脉冲光(IPL)光动力疗法(5-ALA-IPL-PDT)对成纤维细胞分泌表型的影响及其信号通路机制.方法:成纤维细胞接种至培养板,采用不同浓度的5-ALA处理细胞2 h后给予不同剂量的IPL辐照.免疫印迹法(Western-blot)观察有丝分裂原活化蛋白激酶(MAPK)相关家族成员[细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)、P38]的蛋白磷酸化水平.ELISA法检测转化生长因子(TGF)-β1、基质金属蛋白酶(MMP)-1水平的变化.结果:①与空白组比较,IPL+ALA(0.5 mmol/L)组、IPL+ALA(1.0 mmol/L)组,MMP-1浓度分别增加94.7%和111.4%,而TGF-β1浓度分别降低34.8%和39.1%(P < 0.05);②IPL+ALA(0.5 mmol/L)组与IPL组比较,ERK、P38和JNK分别增加113.1%、36.1%和67.3%(P < 0.05).结论:5-ALA-IPL-PDT可刺激MAPK家族分子(ERK、P38、JNK)的活化,诱导成纤维细胞MMP-1的分泌,而抑制TGF-β1的分泌.%Objectives: To study the influence of 5-ALA-IPL-PDT on the MAPK pathway and the secretion of MMP-1, TGF-(31 in fibroblasts. Methods: The fibroblasts were inoculated onto the culture plates. Two hours before IPL radiation dif ferent doses of 5 -aminolevulinic acid (5-ALA) were added to the plate. The level of MAPK phosphorylation was examined by Western blotting. The levels of TGF-(31 and MMP-1 were assessed with enzyme-linked immunosorbent assay (ELISA). Results: CD Compared with control groups, the expressions of MMP-1 in IPL iO J/cm2)+ALA(0.5 mmol/L) groups and IPL 10 J/cm2)+ALA(1.0 mmol/L) groups were markedly enhanced by 94.7% and 111.4%, While the expressions of TGF-(31 dropped by 34.8% and 39.1%, respectively (P < 0.05). ?Compared with IPL groups, IPL 10 J/cm2)+ALA (0.5 mmol/L) increased the phosphorylation of MAPK(ERK,P38 and JNK), up to 113.1%, 36.1% and 67.3%, respectively. Conclusions: 5-ALA-IPL-PDT stimulates MAPK ( ERK, P38 and JNK) phosphorylation in fibroblasts, a potential mechanism involved in downregulating the

  4. Treatment of ichthyophthiriasis with photodynamically active chlorophyllin.

    Science.gov (United States)

    Häder, D-P; Schmidl, J; Hilbig, R; Oberle, M; Wedekind, H; Richter, P R

    2016-04-01

    Water-soluble chlorophyll (chlorophyllin) exerts pronounced photodynamic activity on fish parasites. In order to determine its potential as a remedy against ectoparasites in fish carps were incubated in water with defined concentrations of chlorophyllin. The main focus of the experiments was on the ciliate Ichthyophthirius multifiliis (Fouquet) which is responsible for considerable losses in livestock in aquaculture. As malachite green, which in the past efficiently cured infected fishes, is banned because of its possible carcinogenicity; no effective remedy is presently available in aquaculture to treat ichthyophthiriasis. Using chlorophyllin, the number of trophonts was significantly reduced (more than 50 %) after 3 h incubation of infested fish at 2 and 4 mg/L and subsequent irradiation with simulated solar radiation. The lack of reinfection after light treatment indicates that also the remaining parasites have lost their multiplication capacity. In the controls (no chlorophyllin and no light, light but no chlorophyllin, or chlorophyllin but no light), no reduction of the I. multifiliis infection was observed. We propose that chlorophyllin (or other photodynamic substances) is a possible effective countermeasure against I. multifiliis and other ectoparasites in aquaculture.

  5. Fighting fish parasites with photodynamically active chlorophyllin.

    Science.gov (United States)

    Häder, D-P; Schmidl, J; Hilbig, R; Oberle, M; Wedekind, H; Richter, P

    2016-06-01

    Water-soluble chlorophyll (chlorophyllin) was used in a phototoxic reaction against a number of fish ectoparasites such as Ichtyobodo, Dactylogyrus, Trichodina, and Argulus. Chlorophyllin is applied to the water at concentrations of several micrograms per milliliter for a predefined incubation time, and afterwards, the parasites are exposed to simulated solar radiation. Application in the dark caused only little damage to the parasites; likewise, light exposure without the addition of the photosensitizer was ineffective. In Ichthyobodo, 2 μg/mL proved sufficient with subsequent simulated solar radiation to almost quantitatively kill the parasites, while in Dactylogyrus, a concentration of about 6 μg/mL was necessary. The LD50 value for this parasite was 1.02 μg/mL. Trichodina could be almost completely eliminated at 2 μg/mL. Only in the parasitic crustacean Argulus, no killing could be achieved by a photodynamic reaction using chlorophyllin. Chlorophyllin is non-toxic, biodegradable, and can be produced at low cost. Therefore, we propose that chlorophyllin (or other photodynamic substances) are a possible effective countermeasure against several ectoparasites in ponds and aquaculture since chemical remedies are either forbidden and/or ineffective.

  6. History of photodynamic therapy in Great Britain.

    Science.gov (United States)

    Mitton, D; Ackroyd, R

    2005-12-01

    Although the concept photodynamic therapy has been recognised for over a century, it is only over the last 25 years that it has been used in Great Britain. The first applications in the UK were in 1981 by John Carruth, who treated patients with advanced ENT and skin cancers. The following year, he and Stephen Bown set up the British Medical Laser Association (BMLA). Since that time, the use of PDT in the UK has slowly expanded in all fields of medicine and surgery. In 1986, Bown set up the National Medical Laser Centre (NMLC) and later collaborated with Liverpool gastroenterologist, Neville Krasner, in animal studies on rat colon. In 1997, Keyvan Moghissi founded the Yorkshire Laser Centre (YLC) and began treating patients with advanced inoperable bronchial and oesophageal cancers. Stan Brown in Leeds set up the Centre for Photobiology and Photodynamic Therapy at the University of Leeds, working in close collaboration with the Yorkshire Cancer Research Centre. Other pioneers include Hugh Barr in Gloucester, Colin Hopper in London, Grant Fullarton in Glasgow and Roger Ackroyd, Malcolm Reed and Nicky Brown in Sheffield. PDT has now been used in the UK in the treatment of skin, oral, ENT, oesophageal, lung, bladder and gynaecological malignancies.

  7. 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.

  8. 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.

  9. Drug Carrier for Photodynamic Cancer Therapy

    Science.gov (United States)

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    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. PMID:26389879

  10. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies

    Directory of Open Access Journals (Sweden)

    Biniam Kidane

    2016-01-01

    Full Text Available Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.

  11. Ozone-photodynamic effect in the experiment in vitro

    Science.gov (United States)

    Loginov, L. E.; Budzinsky, A. A.; Torshina, Nadezgda L.; Posypanova, Anna M.; Volkova, Anna I.

    1996-12-01

    With the purpose of increased photodestruction oncocells we develop a method of ozone-photodynamic therapy. As a target cell for laser processing we are using photosensibilitable erythrocytes of integral blood patient, past seance of ozonetherapy.

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

    CSIR Research Space (South Africa)

    Van Kets, V

    2010-09-01

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

  13. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies.

    Science.gov (United States)

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-21

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.

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

    OpenAIRE

    Е. V. Filonenko; Sokolov, V. V.; Е. S. Karpova

    2013-01-01

    The experience of photodynamic therapy for early gastric cancer is described in the article. The treatment results in 68 patients who were excluded for convenient surgical treatment because of advanced age or severe co-morbidity are represented. 63 patients had single tumor, 5 patients – 2 tumors. Four Russian agents: photogem, photosens, radaсhlorin and alasens, were used for photodynamic therapy. The treatment session was performed under local anesthesia during routine endoscopy with diode ...

  15. [Photodynamic reaction and oxidative stress - influence of the photodynamic effect on the activity antioxidant enzymes].

    Science.gov (United States)

    Romiszewska, Anna; Nowak-Stępniowska, Agata

    2014-01-01

    The interaction of light with a photosensitizer, accumulated in a tissue in the presence of oxygen, leads to formation of reactive oxygen species, mainly of singlet oxygen and free radicals. These factors react with biomolecules producing their oxidized states. Reactive oxygen species, such as singlet oxygen and free radicals are able to damage membranes, DNA, enzymes, structural peptides and other cellular structures leading to cell death. An antioxidant protection of cell is formed by enzymes belonging to the family of oxidoreductases: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). Photodynamic therapy leads to the increased production of oxidizing toxic forms. It is important to analyze impact of PDT on the activity of antioxidant enzymes, such as SOD, CAT, GPx. The activity of antioxidant enzymes during the photodynamic effect is influenced by both the light energy dose and the concentration of photosensitizer. The presence only of the photosensitizer or only the light energy may also result in changes in the activity of these enzymes. The differences in changes in the activity of these enzymes depend on the type of used photosensitizer. A phenomenon of selective accumulation of photosensitizer in tumor tissues is used in the photodynamic method of tumor diagnosis and treatment.

  16. Graphene-based nanovehicles for photodynamic medical therapy

    Directory of Open Access Journals (Sweden)

    Li Y

    2015-03-01

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

  17. 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

  18. 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.

  19. Construction and Evaluation of a Targeted Hyaluronic Acid Nanoparticle/Photosensitizer Complex for Cancer Photodynamic Therapy.

    Science.gov (United States)

    Gao, Shi; Wang, Jingjing; Tian, Rui; Wang, Guohao; Zhang, Liwen; Li, Yesen; Li, Lu; Ma, Qingjie; Zhu, Lei

    2017-09-12

    Photodynamic therapy (PDT) is a novel treatment modality that is under intensive preclinical investigations for a variety of diseases, including cancer. Despite extensive studies in this area, selective and effective photodynamic agents that can specifically accumulate in tumors to reach a therapeutic concentration are limited. Although recent attempts have produced photosensitizers (PSs) complexed with various nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy hamper their utilization. Here, we developed a CD44-targeted nanophotodynamic agent by physically encapsulating a photosensitizer, Ce6, into a hyaluronic acid nanoparticle (HANP), which was hereby denoted HANP/Ce6. Its physical features and capability for photodynamic therapy were characterized in vitro and in vivo. Systemic delivery of HANP/Ce6 resulted in its accumulation in a human colon cancer xenograft model. The tumor/muscle ratio reached 3.47 ± 0.46 at 4 h post injection, as confirmed by fluorescence imaging. Tumor growth after HANP/Ce6 treatment with laser irradiation (0.15 W/cm(2), 630 nm) was significantly inhibited by 9.61 ± 1.09-fold compared to that in tumor control groups, which showed no change in tumor growth. No apparent systemic and local toxic effects on the mice were observed. HANP/Ce6-mediated tumor growth inhibition was accessed and observed for the first time by (18)F-fluoro-2-deoxy-d-glucose positron emission tomography as early as 1 day after treatment and persisted for 14 days within our treatment time window. In sum, our results highlight the imaging properties and therapeutic effects of the novel HANP/Ce6 theranostic nanoparticle for CD44-targeted PDT cancer therapy that may be potentially utilized in the clinic. This HANP system may also be applied for the delivery of other hydrophobic PSs, particularly those that could not be chemically modified.

  20. Photodynamic Cancer Therapy—Recent Advances

    Science.gov (United States)

    Abrahamse, Heidi

    2011-09-01

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

  1. Basic experimental research on methylene blue-mediated photody-namic therapy combined with adriamycin for breast carcinoma%亚甲蓝光动力疗法联合阿霉素治疗乳腺癌的实验研究*

    Institute of Scientific and Technical Information of China (English)

    佟仲生; 刘晓东; 史业辉; 李淑芬; 王忱; 郝春芳

    2013-01-01

      目的:探讨亚甲蓝介导的光动力疗法联合阿霉素对小鼠乳腺癌细胞系4T1的体外及体内抑瘤效应及其相关机制,为临床应用提供理论依据。方法:本研究分为空白对照组、阿霉素组、光动力治疗组及联合治疗组。MTT法检测光动力疗法联合阿霉素对乳腺癌细胞增殖的影响。流式细胞术检测细胞凋亡及坏死情况。Rhodamine123检测线粒体膜电位变化。建立乳腺癌荷瘤小鼠模型,绘制肿瘤生长曲线,观察治疗效果。结果:体外实验表明光动力疗效与光敏剂呈剂量依赖性,而联合阿霉素可以增强抑瘤效应。阿霉素组细胞死亡率较低,光动力治疗组以早期及晚期凋亡为主,联合治疗组以晚期凋亡及坏死为主。与空白对照组比较,光动力治疗组及联合治疗组线粒体膜电位显著降低,差异均有统计学意义(P<0.05),联合治疗组较光动力治疗组线粒体膜电位更低(P<0.05)。体内实验显示光动力疗法可以显著抑制小鼠乳腺癌皮下移植瘤生长,而联合阿霉素可以增强抑瘤作用。结论:亚甲蓝介导的光动力疗法对乳腺癌细胞及移植瘤的生长抑制作用明显,联合阿霉素可增强抑瘤效果。光动力疗法以细胞凋亡为主,其机制可能与降低肿瘤细胞线粒体膜电位相关。%  Objective: This work aimed to investigate the therapeutic efficacy of methylene blue (MB)-mediated photodynamic therapy (PDT) with adriamycin (ADM) on 4T1 mouse mammary carcinoma cells in vitro and in vitro, thereby providing a theoretical ba-sis for clinical applications. Methods: The experimental study was divided into four groups, namely, control (Group One), ADM (Group Two), PDT (Group Three), and therapeutic alliance or PDT+ADM (Group Four). Methyl thiazolyl tetrazolium assay was em-ployed to determine the effects of the combined therapy on the proliferation of breast cancer cells. Cell

  2. A Comprehensive Tutorial on In Vitro Characterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms

    Directory of Open Access Journals (Sweden)

    Tobias Kiesslich

    2013-01-01

    Full Text Available In vitro research performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS intended for application in photodynamic therapy (PDT of cancer or photodynamic inactivation (PDI of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performing in vitro experiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research.

  3. Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.

    Science.gov (United States)

    Chen, Wei-Hua; Lecaros, Rumwald Leo G; Tseng, Yu-Cheng; Huang, Leaf; Hsu, Yih-Chih

    2015-04-01

    Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1α siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1α siRNA nanoparticles effectively reduced HIF1α expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenous injection of the same nanoparticles into human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA accumulation and reduced HIF1α expression in tumor tissues. When combined with photodynamic therapy, HIF1α siRNA nanoparticles enhanced the regression in tumor size resulting in a ~40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1α siRNA or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker studies support this conclusion. Our results show the potential use of LCP nanoparticles for efficient delivery of HIF1α siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

    Science.gov (United States)

    Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

    2011-01-01

    Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154

  6. 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. 

  7. Photodynamic action of hypocrellin A in liposomes

    Institute of Scientific and Technical Information of China (English)

    邹伟; 安静仪; 李滨; 蒋丽金

    1996-01-01

    Hypocrellin A (HA), a perylenequinone derivative, is an efficient phototherapeutic agent. When HA is incorporated into small unilamellar liposomes of egg phosphatidylcholine, it generates 1O2 as demonstrated by 9,10-diphenylanthracene (9,10-DPA) photobleaching and detection of nitroxide radicals with ESR. The 1O2 quantum yield measured is 0.80±0.02. On irradiation of oxygen-saturated solution of HA-liposomes, hydroxyl radical OH is detected using DMPO as the ESR spin trapping agent. Hydroxyl radical is derived from superoxide radical anion O2-. The electron transfer reaction is also studied in deaerated solution. The results suggest that the photodynamic action of HA in lipid membranes proceeds via both Type I and Type II reactions.

  8. [Photodynamic therapy in treatment of chorioid neovascularization].

    Science.gov (United States)

    Avetisov, S E; Budzinskaia, M V; Kiseleva, T N; Kazarian, E E; Gurova, I V; Loshchenov, V B; Shevchik, S A; Kuz'min, S G; Vorozhtsov, G N

    2007-01-01

    The authors studied the effectiveness of photodynamic therapy (PDT) with Photosence, a Russian photosensitizer, in treatment of chorioid neovascularization (CNV) in cases of age-related macular degeneration (ARMD) and pathological myopia (PM). The subjects were 73 patients with CNV suffering from ARMD and PM. The efficiency of PDT and complex conservative therapy was compared using vision acuity measurement, retinal morphometry, and fluorescent eye ground angiography (FEGA), performed before treatment, immediately after treatment, and 1, 3, 6, and 12 months later. The study showed that PDT in patients with CNV, ARMD and PM was more efficient than pharmacotherapy. Vision acuity improved or stabilized, and the parameters of retinal morphometry and FEGA improved as well. The results of the study evidence high efficiency of PDT with Photosence in treatment of CNV with ARMD and PM.

  9. 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.

  10. Interstitial Photodynamic Therapy—A Focused Review

    Science.gov (United States)

    Shafirstein, Gal; Bellnier, David; Oakley, Emily; Hamilton, Sasheen; Potasek, Mary; Beeson, Karl; Parilov, Evgueni

    2017-01-01

    Multiple clinical studies have shown that interstitial photodynamic therapy (I-PDT) is a promising modality in the treatment of locally-advanced cancerous tumors. However, the utilization of I-PDT has been limited to several centers. The objective of this focused review is to highlight the different approaches employed to administer I-PDT with photosensitizers that are either approved or in clinical studies for the treatment of prostate cancer, pancreatic cancer, head and neck cancer, and brain cancer. Our review suggests that I-PDT is a promising treatment in patients with large-volume or thick tumors. Image-based treatment planning and real-time dosimetry are required to optimize and further advance the utilization of I-PDT. In addition, pre- and post-imaging using computed tomography (CT) with contrast may be utilized to assess the response. PMID:28125024

  11. 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.

  12. 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.

  13. Progress of photodynamic therapy in gastric cancer.

    Science.gov (United States)

    Mimura, S; Narahara, H; Otani, T; Okuda, S

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm(2) for an argon dye laser and 60 J/cm(2) for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm(2) in area to 4 cm in diameter, i.e. 13 cm(2) by employing a new excimer dye laser model, which could emit 4mJ/pulse with 80 Hz pulse frequency. (4) The depth of cancer invasion which could be treated by PDT was increased from about 4 mm, i.e. the superficial part of the submucosal layer (SM-1) to more than 10 mm in depth, i.e. the proper muscular layer. These improvements owe much to the pulse laser, the photodynamic action induced by which permits deeper penetration than that of a continuous wave laser. (5) We employed a side-viewing fiberscope for gastric PDT to irradiate the lesion from an angle of 90 degrees . (6) We designed a simple cut quartz fiber for photoradiation with a spiral spring thickened toward the end. (7) We developed an endoscopic device for photoradiation in PDT which achieves accurate and efficient irradiation. As a result of these improvements a higher cure rate was obtained even with a lower light dose of irradiation.

  14. Synthesis and in vitro photodynamic therapy of chlorin derivative 13(1)-ortho-trifluoromethyl-phenylhydrazone modified pyropheophorbide-a.

    Science.gov (United States)

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

    2017-03-01

    Photodynamic therapy (PDT) is entering the mainstream of the cancer treatments recently. Pyropheophorbide-a (Pa), as a degradation product of chlorophyll-a, has been shown to be a potent photosensitizer in photodynamic therapy. In this paper, we investigated the in vitro photodynamic therapy of 13(1)-ortho-trifluoromethyl-phenylhydrazone modified pyropheophorbide-a (PHPa) against human HeLa cervical cancer cell line, together with ultraviolet-visible spectra, fluorescence emission spectra, stability in various solvents, and single oxygen quantum yield. The results indicated that PHPa not only showed a greater molar extinction coefficient reached 4.55×10(4) Lmol(-1)cm(-1), the long absorption wavelength (681nm) as we expected that makes it potential in deep tumor treatment, but also showed better stability in near neutral phosphate buffers (pH 7.4) and culture medium, as well as higher single oxygen quantum yield (ФD=40.5%) in DMF solutions. Moreover, cell experiments suggested that PHPa could be uptaken by HeLa cells successfully, and has low dark toxicity without irradiation, but remarkable photo-cytotoxicity (IC50, 1.92±0.59μM) that the inhibition rate of HeLa cells could increase up 91.4% at 30μM of PHPa after irradiation. In addition, morphological changes of HeLa cells further demonstrated that PHPa can induce damage and apoptotic cell death. Furthermore, the mechanism of photochemical processes was investigated by using specific quenching agent sodium azide (SA) and D-mannitol (DM), respectively, which showed the formation of singlet oxygen (Type II reaction mechanism) may play a predominant role, Type I and Type II photodynamic reactions could occur simultaneously in this PHPa mediated PDT process. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Comparing clinical effects of photodynamic therapy as a novel method with topical corticosteroid for treatment of Oral Lichen Planus.

    Science.gov (United States)

    Bakhtiari, Sedigheh; Mojahedi, Seyyed Masoud; Azari-Marhabi, Saranaz; Namdari, Mahshid; Rankohi, Zahra Elmi

    2017-06-29

    Oral lichen planus is an autoimmune disorder with several challenges in treatment. Photodynamic therapy has been proposed as a new treatment option for the disease. The present study compared the clinical effects of the photodynamic therapy and dexamethasone mouthwash in the treatment of oral lichen planus lesions. In this randomized clinical trial, 30 patients with oral lichen planus were included.15 patients were treated with 5% methylene blue mediated photodynamic therapy using Fotosan device for 30seconds (630nm wavelength and 7.2-14.4J/CM2 dose) for 4 sessions in the days 1,4,7,14. In another group, the treatment was done on 15 patients by 0.5mg tab dexamethasone solution in 5cc water, rinsed 4 times in a day within two weeks. The sign score, symptoms scores (pain), clinical severity and treatment efficacy were measured at the days 15,30,60,90 after beginning of the treatment. The results were subjected to Mann-whitney U test in both groups. No significant difference existed between two modalities regarding the treatment efficacy index, sign score, symptom score and clinical severity on the 15, 30, 60 and 90 post-treatment days. Decreases in patient's symptoms were statistically significant in both groups. Photodynamic therapy was as effective as the dexamethasone mouth wash in the treatment of oral lichen planus It could be used as a safe modality in the treatment of oral lichen planus lesions without identified side effects. Copyright © 2017. Published by Elsevier B.V.

  16. Cellular changes, molecular pathways and the immune system following photodynamic treatment.

    Science.gov (United States)

    Skupin-Mrugalska, P; Sobotta, L; Kucinska, M; Murias, M; Mielcarek, J; Düzgüneş, N

    2014-01-01

    Photodynamic therapy (PDT) is a novel medical technique involving three key components: light, a photosensitizer molecule and molecular oxygen, which are essential to achieve the therapeutic effect. There has been great interest in the use of PDT in the treatment of many cancers and skin disorders. Upon irradiation with light of a specific wavelength, the photosensitizer undergoes several reactions resulting in the production of reactive oxygen species (ROS). ROS may react with different biomolecules, causing defects in many cellular structures and biochemical pathways. PDT-mediated tumor destruction in vivo involves cellular mechanisms with photodamage of mitochondria, lysosomes, nuclei, and cell membranes that activate apoptotic, necrotic and autophagic signals, leading to cell death. PDT is capable of changing the tumor microenvironment, thereby diminishing the supply of oxygen, which explains the antiangiogenic effect of PDT. Finally, inflammatory and immune responses play a crucial role in the long-lasting consequences of PDT treatment. This review is focused on the biochemical effects exerted by photodynamic treatment on cell death signaling pathways, destruction of the vasculature, and the activation of the immune system.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy.

    Science.gov (United States)

    Schneider, Raphaël; Schmitt, Frédéric; Frochot, Céline; Fort, Yves; Lourette, Natacha; Guillemin, François; Müller, Jean-François; Barberi-Heyob, Muriel

    2005-04-15

    Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by 1H NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates 1 and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates 1 and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm2, respectively.

  2. 5-氨基酮戊酸介导的光动力疗法预防兔耳瘢痕增生的初步探讨%Prevention of hypertrophic scars by 5 -aminolaevulinic acid-mediated photodynamic therapy in a rabbit ear model

    Institute of Scientific and Technical Information of China (English)

    胡丽; 李昕; 黄惠真; 李伟

    2014-01-01

    目的:探讨5-氨基酮戊酸介导的光动力疗法抑制兔耳瘢痕增生的效果。方法建立兔耳增生性瘢痕模型后,将108个增生性瘢痕块随机分为4组:空白对照组、单纯激光组、单纯5-氨基酮戊酸组及5-氨基酮戊酸介导的光动力治疗组。5-氨基酮戊酸介导的光动力治疗组在局部注射5-氨基酮戊酸后5 h 行半导体激光照射,波长635 nm,功率密度100 mW/cm2,照射20 min。治疗后观察3周瘢痕的生长情况,测量瘢痕厚度及红斑指数,取材后行 HE 染色,观察真皮层厚度的变化,计算各组瘢痕增生指数, Masson 染色观察胶原纤维排列情况,TUNEL 染色观察成纤维细胞凋亡情况。结果5-氨基酮戊酸介导的光动力治疗组瘢痕厚度与红斑指数较其他3组均降低(P <0.05);真皮层厚度明显变薄,瘢痕增生指数较其他3组明显降低(P <0.05);Masson 染色显示,5-氨基酮戊酸介导的光动力治疗组真皮层内胶原纤维较其他3组减少,且排列整齐有序;TUNEL 染色显示,5-氨基酮戊酸介导的光动力治疗组成纤维细胞凋亡数量较其他3组明显增多(P <0.05)。结论应用5-氨基酮戊酸介导的光动力疗法可以预防兔耳瘢痕增生。%Objective To investigate the effects of 5 - aminolaevulinic acid- mediated photodynamic therapy (ALA-PDT)on hypertrophic scars in a rabbit ear model.Methods The acute model of dermal hypertrophic scar was established in the rabbit ears.Totally 108 scar wounds were randomly divided into 4 groups:the blank control group,the laser treatment group,the ALA injection group and the ALA-PDT group.In the ALA-PDT group,5 h after intra-dermal injection of ALA,the scars were irradia-ted at 635 nm wavelength, 100 mW/cm2 for 20 min.Three weeks after treatment,the scars thickness and erythema index were measured,and the specimens were harvested for histological analysis by HE and Masson staining.Results The thickness,erythema index and the scar elevation

  3. 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.

  4. 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.

  5. Sono-photodynamic combination therapy: a review on sensitizers.

    Science.gov (United States)

    Sadanala, Krishna Chaitanya; Chaturvedi, Pankaj Kumar; Seo, You Mi; Kim, Jeung Mo; Jo, Yong Sam; Lee, Yang Koo; Ahn, Woong Shick

    2014-09-01

    Cancer is characterized by the dysregulation of cell signaling pathways at several steps. The majority of current anticancer therapies involve the modulation of a single target. A tumor-targeting drug-delivery system consists of a tumor detection moiety and a cytotoxic material joined directly or through a suitable linker to form a conjugate. Photodynamic therapy has been used for more than 100 years to treat tumors. One of the present goals of photodynamic therapy research is to enhance the selective targeting of tumor cells in order to reduce the risk and extension of unwanted side-effects, caused by normal cell damage. Sonodynamic therapy is a promising new treatment for patients with cancer. It treats cancer with ultrasound and sonosensitive agents. Porphyrin compounds often serve as photosensitive and sonosensitive agents. The combination of these two methods makes cancer treatment more effective. The present review provides an overview of photodynamic therapy, sonodynamic therapy, sono-photodynamic therapy and the four sensitizers which are suitable candidates for combined sono-photodynamic therapy. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Comparison microbial killing efficacy between sonodynamic therapy and photodynamic therapy

    Science.gov (United States)

    Drantantiyas, Nike Dwi Grevika; Astuti, Suryani Dyah; Nasution, Aulia M. T.

    2016-11-01

    Biofilm is a way used by bacteria to survive from their environmental conditions by forming colony of bacteria. Specific characteristic in biofilm formation is the availability of matrix layer, known as extracellular polymer substance. Treatment using antibiotics may lead bacteria to be to resistant. Other treatments to reduce microbial, like biofilm, can be performed by using photodynamic therapy. Successful of this kind of therapy is induced by penetration of light and photosensitizer into target cells. The sonodynamic therapy offers greater penetrating capability into tissues. This research aimed to use sonodynamic therapy in reducing biofilm. Moreover, it compares also the killing efficacy of photodynamic therapy, sonodynamic therapy, and the combination of both therapeutic schemes (known as sono-photodynamic) to achieve higher microbial killing efficacy. Samples used are Staphylococcus aureus biofilm. Treatments were divided into 4 groups, i.e. group under ultrasound treatment with variation of 5 power levels, group of light treatment with exposure of 75s, group of combined ultrasound-light with variation of ultrasound power levels, and group of combined lightultrasound with variation of ultrasound power levels. Results obtained for each treatment, expressed in % efficacy of log CFU/mL, showed that the treatment of photo-sonodynamic provides greater killing efficacy in comparison to either sonodynamic and sono-photodynamic. The photo-sonodynamic shows also greater efficacy to photodynamic. So combination of light-ultrasound (photo-sonodynamic) can effectively kill microbial biofilm. The combined therapy will provide even better efficacy using exogenous photosensitizer.

  7. Mitochondria-targeting for improved photodynamic therapy

    Science.gov (United States)

    Ngen, Ethel J.

    Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus

  8. Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release of Damage-Associated Molecular Patterns (DAMPs) in human HeLa cells.

    Science.gov (United States)

    Panzarini, Elisa; Inguscio, Valentina; Fimia, Gian Maria; Dini, Luciana

    2014-01-01

    The new concept of Immunogenic Cell Death (ICD), associated with Damage Associated Molecular Patterns (DAMPs) exposure and/or release, is recently becoming very appealing in cancer treatment. In this context, PhotoDynamic Therapy (PDT) can give rise to ICD and to immune response upon dead cells removal. The list of PhotoSensitizers (PSs) able to induce ICD is still short and includes Photofrin, Hypericin, Foscan and 5-ALA. The goal of the present work was to investigate if Rose Bengal Acetate (RBAc), a powerful PS able to trigger apoptosis and autophagy, enables photosensitized HeLa cells to expose and/or release pivotal DAMPs, i.e. ATP, HSP70, HSP90, HMGB1, and calreticulin (CRT), that characterize ICD. We found that apoptotic HeLa cells after RBAc-PDT exposed and released, early after the treatment, high amount of ATP, HSP70, HSP90 and CRT; the latter was distributed on the cell surface as uneven patches and co-exposed with ERp57. Conversely, autophagic HeLa cells after RBAc-PDT exposed and released HSP70, HSP90 but not CRT and ATP. Exposure and release of HSP70 and HSP90 were always higher on apoptotic than on autophagic cells. HMGB1 was released concomitantly to secondary necrosis (24 h after RBAc-PDT). Phagocytosis assay suggests that CRT is involved in removal of RBAc-PDT generated apoptotic HeLa cells. Altogether, our data suggest that RBAc has all the prerequisites (i.e. exposure and/or release of ATP, CRT, HSP70 and HSP90), that must be verified in future vaccination experiments, to be considered a good PS candidate to ignite ICD. We also showed tha CRT is involved in the clearance of RBAc photokilled HeLa cells. Interestingly, RBAc-PDT is the first cancer PDT protocol able to induce the translocation of HSP90 and plasma membrane co-exposure of CRT with ERp57.

  9. Photodynamic inactivation of prions by disulfonated hydroxyaluminium phthalocyanine.

    Science.gov (United States)

    Janouskova, Olga; Rakusan, Jan; Karaskova, Marie; Holada, Karel

    2012-11-01

    Sulfonated phthalocyanines (Pcs) are cyclic tetrapyrroles that constitute a group of photosensitizers. In the presence of visible light and diatomic oxygen, Pcs produce singlet oxygen and other reactive oxygen species that have known degradation effects on lipids, proteins and/or nucleic acids. Pcs have been used successfully in the treatment of bacterial, yeast and fungal infections, but their use in the photodynamic inactivation of prions has never been reported. Here, we evaluated the photodynamic activity of the disodium salt of disulfonated hydroxyaluminium phthalocyanine (PcDS) against mouse-adapted scrapie RML prions in vitro. PcDS treatment of RML brain homogenate resulted in a time- and dose-dependent inactivation of prions. The photodynamic potential of Pcs offers a new way to inactivate prions using biodegradable compounds at room temperature and normal pressure, which could be useful for treating thermolabile materials and liquids.

  10. Influence of bacterial interactions on the susceptibility to photodynamic inactivation

    Science.gov (United States)

    Upadya, M. H.; Tegos, G.; Hamblin, M.; Kishen, A.

    2009-06-01

    Photodynamic therapy has emerged as a possible supplement to the existing protocols for endodontic disinfection. Microbes are known to gain significant ecological advantage when they survive as coaggregates and biofilms in an infected tissue. Such microbial coaggregates and biofilms have been confirmed to play a key role in the pathogenicity of many infections. So far, not many studies have correlated the efficacy of antimicrobial photodynamic inactivation (APDI) to the different modes of bacterial growth. This study aims to evaluate the APDI of 3 strains of Enterococcus faecalis in planktonic phase, in a co-aggregated suspension and in a 4-day old biofilm. The results showed that the biofilm mode of growth offered the greatest resistance to APDI and the inclusion of an efflux pump inhibitor significantly increased the APDI of biofilm bacteria. From this study, we conclude that APDI of bacteria in biofilms is the most challenging and that the use of bacterial efflux pump inhibitors enhances its photodynamic antibiofilm efficacy.

  11. 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.

  12. Photodynamic therapy in treatment of cutaneous and choroidal melanoma.

    Science.gov (United States)

    Kawczyk-Krupka, Aleksandra; Bugaj, Andrzej M; Latos, Wojciech; Zaremba, Katarzyna; Sieroń, Aleksander

    2013-12-01

    Melanoma is a malignant, the most aggressive and dreaded skin cancer. This form of cancer arises from melanocytes and may grow rapidly and metastasize. Melanoma predominantly occurs in skin, but could also be found in the mouth, iris and retina of the eye. Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. It is highly resistant to traditional chemotherapy and radiotherapy, although modern biological therapies are showing some promise. Photodynamic therapy (PDT), as a novel effective modality of the treatment of skin cancers, opens up new possibilities in melanoma treatment also. Many experimental photodynamic therapy studies were performed. The results of many experiments indicate that that photodynamic therapy may be a promising tool for adjuvant treatment in advanced melanoma. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. [Photophysical properties and photodynamic activity of nanostructured aluminium phthalocyanines].

    Science.gov (United States)

    Udartseva, O O; Lobanov, A V; Andeeva, E R; Dmitrieva, G S; Mel'nikov, M Ia; Buravkova, L B

    2014-01-01

    We developed water-soluble supramolecular complexes of aluminium phthalocyanine based on mesoporous silica nanoparticles and polyvinylpirrolidone containing rare photoactive nanoaggregates. Radiative lifetimes, extinction coefficients and energy of electronic transitions of isolated and associated metal phthalocyanine complexes were calculated. Nontoxic concentrations of synthesized nanocomposite photosensibilizers were in vitro determined. In present study we compared photodynamic treatment efficacy using different modifications of aluminium phthalocyanine (Photosens®, AlPc-nSiO2 and AlPc-PVP). Mesenchymal stromal cells were used as a model for photodynamic treatment. Intracellular accumulation of aluminium phthalocyanine based on mesoporous silica nanoparticles AlPc-nSiO2 was the most efficient. Illumination of phthalocyanine-loaded cells led to reactive oxygen species generation and subsequent apoptotic cell death. Silica nanoparticles provided a significant decrease of effective phthalocyanine concentration and enhanced cytotoxicity of photodynamic treatment.

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

    Directory of Open Access Journals (Sweden)

    Yu-Chao Chang

    2013-03-01

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

  15. Photodynamic therapy of cervical intraepithelial neoplasia using hexaminolevulinate and methylaminolevulinate

    Science.gov (United States)

    Soergel, Philipp; Staboulidou, Ismini; Hertel, Herrmann; Schippert, Cordula; Hillemanns, Peter

    2009-06-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer. Previous studies indicated that photodynamic therapy (PDT) represents an effective treatment modality in CIN. In 28 patients with CIN 1 - 3, 1 - 2 cycles of PDT were conducted using hexaminolevulinate (HAL) or methylaminolevulinate (MAL) and a special light delivery system. After 6 months, biopsies were obtained to assess response. The overall response rate for complete or partial response was 65%. Photodynamic therapy using new ALA esters is effective and may offer unique advantages in the therapy of CIN.

  16. Photodynamic antibacterial effect of graphene quantum dots.

    Science.gov (United States)

    Ristic, Biljana Z; Milenkovic, Marina M; Dakic, Ivana R; Todorovic-Markovic, Biljana M; Milosavljevic, Momir S; Budimir, Milica D; Paunovic, Verica G; Dramicanin, Miroslav D; Markovic, Zoran M; Trajkovic, Vladimir S

    2014-05-01

    Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.

  17. Novel Photodynamics in Phytochrome & Cyanobacteriochrome Photosensory Proteins

    Science.gov (United States)

    Larsen, Delmar

    2015-03-01

    The photodynamics of recently characterized phytochrome and cyanobacteriochrome photoreceptors are discussed. Phytochromes are red/far-red photosensory proteins that utilize the photoisomerization of a linear tetrapyrrole (bilin) chromophore to detect the red to far-red light ratio. Cyanobacteriochromes (CBCRs) are distantly related cyanobacterial photosensors with homologous bilin-binding GAF domains, but exhibit greater spectral diversity. The excited-state mechanisms underlying the initial photoisomerization in the forward reactions of the cyanobacterial photoreceptor Cph1 from Synechocystis, the RcaE CBCR from Fremyella diplosiphon, and Npr6012g4 CBCR from Nostoc punctiforme were contrasted via multipulse pump-dump-probe transient spectroscopy. A rich excited-state dynamics are resolved involving a complex interplay of excited-state proton transfer, photoisomerization, multilayered inhomogeneity, and reactive intermediates, and Le Chatelier redistribution. NpR6012g4 exhibits a high quantum yield for its forward photoreaction (40%) that was ascribed to the activity of hidden, productive ground-state intermediates via a ``second chance initiation dynamics'' (SCID) mechanism. This work was supported by a grant from the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, United States Department of Energy (DOE DE-FG02-09ER16117).

  18. 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.

  19. 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.

  20. 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.

  1. 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) ).

  2. 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.

  3. Photodynamic antimicrobial polymers for infection control.

    Directory of Open Access Journals (Sweden)

    Colin P McCoy

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

  4. 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.

  5. Preliminary study of verteporfin photodynamic therapy in a canine prostate model

    Science.gov (United States)

    Huang, Zheng; Hetzel, Fred; Dole, Ken; Luck, David; Beckers, Jill; Maul, Don

    2009-06-01

    Photodynamic therapy (PDT) mediated with verteporfin was investigated as an alternative modality for the treatment of prostate cancer. Materials and Methods: Vertoporfin-mediated photodynamic effects on the prostate and its adjacent structures (underlying colon and bladder) were evaluated in a healthy canine model. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (689 nm) and 1-cm cylindrical diffuser fibers at various light doses and drug-light intervals (DLI) to activate the IV administrated photosensitizer (0.5 or 2 mg/kg). The sensitivity of the adjacent tissues to Vertoporfin-PDT was determined by superficially irradiating the serosal surface of the bladder and colon with a microlens fiber. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathological examination. Results: Histopathological examinations confirmed that verteporfin PDT could destroy a clinically significant volume of prostatic tissue in the animal model. At the drug dose of 0.5 mg/kg, the light irradiation of 100 J/cm could induce a lesion diameter of 2 cm at DLI of 15 min and 1.2 cm at DLI of 3 hrs, respectively. This implies a strong influence of DLI on the lesion volume. The shorter DLI might produce stronger vascular effect and therefore more severe tissue damage. The colon was more sensitive to verteporfin PDT than the bladder. At the possible light dose level caused by light scattering during intra-prostate irradiation, the damage to the bladder and colon were superficial and minimal. Conclusions: The preliminary results clearly demonstrate that verteporfin PDT could be an effective means to destroy prostate gland and its usefulness for the treatment of prostate cancer is worth further investigation.

  6. 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.

  7. Redox Proteomics Sheds Light on Photodynamic Treatment of Cancer

    NARCIS (Netherlands)

    Tsaytler, P.A.

    2009-01-01

    Cancer is the second most common cause of death among humans in the world, exceeded only by heart disease. One of the promising modalities for the treatment of cancer is photodynamic therapy (PDT). It is based on the concept that (1) certain light-sensitive compounds (photosensitizers) can be locali

  8. Photodynamic therapy for actinic keratosis in organ transplant patients

    DEFF Research Database (Denmark)

    Basset-Seguin, N; Baumann Conzett, K; Gerritsen, M J P

    2013-01-01

    of the immunosuppressant drugs. Conventional therapies for AK, using curettage, cryotherapy, surgical excision, topical therapies and photodynamic therapy (PDT), are often less effective, and may be inappropriate, for treating the greater numbers and extent of lesions in OTRs. Moreover, there are no specific protocols...

  9. 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

  10. Pathogen inactivation in cellular blood products by photodynamic treatment

    NARCIS (Netherlands)

    Trannoy, Laurence Liliane

    2010-01-01

    The safety of blood transfusion can be increased by introducing methods that eliminate blood-borne pathogens such as viruses and bacteria. In this thesis, the use of photodynamic treatment (PDT) to inactivate pathogens in cellular blood products is described. Various photosensitizers, from phenothia

  11. 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

  12. 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

  13. Active and passive control of zinc phthalocyanine photodynamics

    NARCIS (Netherlands)

    Sharma, D.; Huijser, J.M.; Savolainen, J.; Steen, G.W.; Herek, J.L.

    2013-01-01

    In this work we report on the ultrafast photodynamics of the photosensitizer zinc phthalocyanine (ZnPc) and manipulation thereof. Two approaches are followed: active control via pulse shaping and passive control via strategic manipulation in the periphery of the molecular structure. The objective of

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

    Directory of Open Access Journals (Sweden)

    Yogesh Doshi

    2010-01-01

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

  15. Photodynamic activity of tetraazachlorin derivate studied in vivo

    Directory of Open Access Journals (Sweden)

    V. I. Ivanova-Radkevich

    2013-01-01

    Full Text Available The results of investigation for photodynamic activity of new tetraazachlorin derivate – tetramethyltribenzotetraazachlorin, synthesized in Research Institute of Organic Intermediates and Dyes. The study was performed on female mice of СВА line. The tumor model was transferred solid ascetic sarcoma S-37. The samples of photosensitizer, previously solubilized in 10% aqueou s solution ofCremophor EL, injected to mice intravenously on the 7th day of tumor growth in dose of 1–2 mg/kg. Two hours later the irradiation of sensitized tumor using light emitting diode device in a maximal wavelength of 755 nm (light power density – 50 mW/cm2, maximal total light dose – 300 J/cm2 was performed. The efficacy of photodynamic therapy was assessed by growth inhibition rates in the study group comparing with control group. The study showed that photodynamic therapy with investigated sample in dose of 2 mg/kg and light dose of 300 J/cm2 significantly inhibited the tumor growth (inhibition rate of 70–80% within 20 days, indicating prospectivity of subsequent investigations of tetraazachlorin as photosensitizer for photodynamic therapy of malignant tumors. 

  16. Light delivery and light dosimetry for photodynamic therapy

    NARCIS (Netherlands)

    W.M. Star (W.)

    1990-01-01

    markdownabstractAbstract Photodynamic therapy (PDT) has attracted attention because it was considered to be a selective form of cancer treatment causing minimal damage to normal tissues. This is not exactly true, because the ratio between the photosensitizer concentrations in tumour and surroundin

  17. Redox Proteomics Sheds Light on Photodynamic Treatment of Cancer

    NARCIS (Netherlands)

    Tsaytler, P.A.|info:eu-repo/dai/nl/304837679

    2009-01-01

    Cancer is the second most common cause of death among humans in the world, exceeded only by heart disease. One of the promising modalities for the treatment of cancer is photodynamic therapy (PDT). It is based on the concept that (1) certain light-sensitive compounds (photosensitizers) can be

  18. Photodynamic therapy in the treatment of vulvar lichen sclerosus.

    Science.gov (United States)

    Maździarz, Agnieszka; Osuch, Beata; Kowalska, Magdalena; Nalewczyńska, Agnieszka; Śpiewankiewicz, Beata

    2017-09-01

    Vulvar lichen sclerosus is a chronic and incurable disease that causes various unpleasant symptoms and serious consequences. The purpose of the study was to assess the effectiveness of photodynamic therapy in the treatment of vulvar lichen sclerosus. Participants in the study included 102 female patients aged 19-85 suffer from vulvar lichen sclerosus. The patients underwent photodynamic therapy (PDT). In the course of PDT the 5% 5- aminolevulinic acid was used in gel form. The affected areas were irradiated with a halogenic lamp PhotoDyn 501 (590-760nm) during a 10-min radiation treatment. The treatment was repeated weekly for 10 weeks. PDT has brought about a good therapeutic effect (complete or partial clinical remission), with 87.25% improvement rate in patients suffering from lichen sclerosus. The greatest vulvoscopic response was observed in the reduction of subepithelial ecchymoses and teleangiectasia (78.95%), and the reduction of erosions and fissures (70.97%). A partial remission of lichenification with hyperkeratosis was observed in 51.61% of cases. The least response was observed in the atrophic lesions reduction (improvement in 37.36% of cases). Our patients suffering from vulvar lichen sclerosus demonstrated positive responses to photodynamic therapy and the treatment was well tolerated. Photodynamic therapy used to treat lichen sclerosus yields excellent cosmetic results. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. New strategies to enhance photodynamic therapy for solid tumors

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    Е. V. Filonenko

    2013-01-01

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

  1. Mechanisms of Resistance to Photodynamic Therapy

    Science.gov (United States)

    Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

    2013-01-01

    Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

  2. 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...

  3. 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

    Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 +/- 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser irradiation. The AHP@MNPs can target tumors via CD44 receptor-mediated endocytosis, which have enhanced tumor therapeutic effects through photodynamic/hyperthermia-combined treatment without any drugs. We successfully detected tumors implanted in mice via magnetic resonance imaging and optical imaging. Furthermore, we demonstrated the photodynamic/hyperthermia-combined therapeutic efficacy of AHP@MNPs with synergistically enhanced efficacy against cancer.Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 +/- 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser

  4. Photodynamic therapy for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Friedberg, Joseph S; Glatstein, Eli; Stevenson, James P; Sterman, Daniel H; Hahn, Stephen M; Cengel, Keith A

    2012-02-01

    Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.

  5. Enhancement of photodynamic therapy effect by temporally inhibiting infarction with anticoagulant heparin

    Science.gov (United States)

    Yang, Liyong; Zhao, Hongyou

    2008-12-01

    Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.

  6. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3

    Science.gov (United States)

    Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M.; Busch, Theresa M.; Cengel, Keith A.

    2012-01-01

    Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT-mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT-mediated activation of EGFR were also observed in response to BPD-mediated PDT in multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and was observed to occur in response to porfimer sodium-mediated PDT. In addition, we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR association and that inhibiting STAT3 signaling prior to PDT leads to increased PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to increased PDT cytotoxicity through a mechanism that involves increased apoptotic cell death. Taken together, these results demonstrate that PDT stimulates the nuclear accumulation of both EGFR and STAT3 and that targeting these survival pathways is a potentially promising strategy that could be adapted for clinical trials of PDT for patients with serosal spread of malignancy. PMID:22986230

  7. Synthesis and characterization of doxorubicin modified ZnO/PEG nanomaterials and its photodynamic action.

    Science.gov (United States)

    Hariharan, R; Senthilkumar, S; Suganthi, A; Rajarajan, M

    2012-11-05

    The aim of this study is to investigate a new strategy of combined application of ZnO/PEG nanospheres with anticancer drug of doxorubicin (DOX) in photodynamic therapy (PDT). We were able to fabricate ZnO/PEG nanospheres as the drug carrier of DOX in drug delivery system. The combination of DOX-ZnO/PEG nanocomposites induced the remarkable improvement in the anti-tumor activity, which has been demonstrated by antibacterial activity, drug release and DNA cleavage study. Furthermore, the possible mechanism was explored by optical spectroscopic studies and EPR - spin trapping technique. It was noted that the photodynamic activity of the non-cytotoxic DOX loaded ZnO/PEG nanocomposite could considerably increase cancer cell injury mediated by reactive oxygen species (ROS) under UV irradiation. In our observations demonstrated that ZnO/PEG nanosphere could obviously increase the intracellular concentration of DOX and enhance its potential anti-tumor efficiency, indicating that ZnO/PEG nanosphere could act as an efficient drug delivery carrier importing DOX into target cancer cells. Nearly 91% of loaded drug was released within 26 h of incubation of conjugates in vitro in an acidic environment. It suggests that there is an efficient drug release of DOX from DOX-ZnO/PEG nanocomposite. DOX loaded on ZnO/PEG nanomaterials showed antibacterial activity was more pronounced with Gram-positive than Gram-negative bacteria under visible light. DOX-ZnO/PEG nanocomposites were effective against HeLa cell lines under in vitro condition and photocleavage of DNA. This result indicated that ZnO/PEG nanomaterials can be used as a nanocarrier for drug delivery system for PDT.

  8. A cell-targeted photodynamic nanomedicine strategy for head and neck cancers.

    Science.gov (United States)

    Master, Alyssa; Malamas, Anthony; Solanki, Rachna; Clausen, Dana M; Eiseman, Julie L; Sen Gupta, Anirban

    2013-05-06

    Photodynamic therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. To this end, we report on a cell-targeted nanomedicine approach for the photosensitizer silicon phthalocyanine-4 (Pc 4), by packaging it within polymeric micelles that are surface-decorated with GE11-peptides to promote enhanced cell-selective binding and receptor-mediated internalization in EGFR-overexpressing H&N cancer cells. Using fluorescence spectroscopy and confocal microscopy, we demonstrate in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N SCC-15 cells. We further demonstrate that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, we demonstrate that the EGFR-targeted Pc 4-nanoformulation results in significant intratumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise toward a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas.

  9. A Cell-targeted Photodynamic Nanomedicine Strategy for Head & Neck Cancers

    Science.gov (United States)

    Master, Alyssa; Malamas, Anthony; Solanki, Rachna; Clausen, Dana M.; Eiseman, Julie L.; Gupta, Anirban Sen

    2013-01-01

    Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. To this end, we report on a cell-targeted nanomedicine approach for the photosensitizer silicon phthalocyanine-4 (Pc 4), by packaging it within polymeric micelles that are surface-decorated with GE11-peptides to promote enhanced cell-selective binding and receptor-mediated internalization in EGFR-overexpressing H&N cancer cells. Using fluorescence spectroscopy and confocal microscopy, we demonstrate in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N SCC-15 cells. We further demonstrate that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, we demonstrate that the EGFR-targeted Pc 4-nanoformulation results in significant intra-tumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas. PMID:23531079

  10. 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

  11. Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy

    Science.gov (United States)

    Pansa, María Florencia; Vera, Renzo Emanuel; Fernández-Zapico, Martín Ernesto; Rumie Vittar, Natalia Belén; Rivarola, Viviana Alicia

    2017-01-01

    Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT. Here, we aimed to examine whether a relationship exists between PDT outcome and ROS-involvement in the resistance mechanism in photosensitized cancer cells. In order to recapitulate tumor architecture of the respective original tumor, we developed a multicellular three-dimensional spheroid system comprising a normoxic periphery, surrounding a hypoxic core. Using Me-ALA, a prodrug of the PS PpIX, in human colorectal spheroids we demonstrate that HIF-1 transcriptional activity was strongly up-regulated and mediates PDT resistant phenotype. RNAi knockdown of HIF-1 impairs resistance to PDT. Oxidative stress-mediated activation of ERK1/2 followed PDT was involved on positive modulation of HIF-1 transcriptional activity after photodynamic treatment. ROS scavenging and MEK/ERK pathway inhibition abrogated the PDT-mediated HIF-1 upregulation. Together our data demonstrate that resistance to PDT is in part mediated by the activation of a ROS-ERK1/2-HIF-1 axis, thus, identifying novel therapeutic targets that could be used in combination with PDT. PMID:28545088

  12. Photodynamic effects of new silicon phthalocyanines: in vitro studies utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources.

    Science.gov (United States)

    Zaidi, S I; Agarwal, R; Eichler, G; Rihter, B D; Kenney, M E; Mukhtar, H

    1993-08-01

    Photodynamic therapy (PDT) of cancer is a modality that relies upon the irradiation of tumors with visible light following selective uptake of a photosensitizer by the tumor tissue. There is considerable emphasis to define new photosensitizers suitable for PDT of cancer. In this study we evaluated six phthalocyanines (Pc) for their photodynamic effects utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources. Of the newly synthesized Pc, two showed significant destruction of cytochrome P-450 and monooxygenase activities, and enhancement of lipid peroxidation, when added to microsomal suspension followed by irradiation with approximately 675 nm light. These two Pc named SiPc IV (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) and SiPc V (HOSiPc-OSi[CH3]2[CH2]3N[CH3]3+I-) showed dose-dependent photodestruction of cytochrome P-450 and monooxygenase activities in liver microsomes, and photoenhancement of lipid peroxidation, lipid hydroperoxide formation and lipid fluorescence in microsomes and erythrocyte ghosts. Compared to chloroaluminum phthalocyanine tetrasulfonate, SiPc IV and SiPc V produced far more pronounced photodynamic effects. Sodium azide, histidine, and 2,5-dimethylfuran, the quenchers of singlet oxygen, afforded highly significant protection against SiPc IV- and SiPc V-mediated photodynamic effects. However, to a lesser extent, the quenchers of superoxide anion, hydrogen peroxide and hydroxyl radical also showed some protective effects. These results suggest that SiPc IV and SiPc V may be promising photosensitizers for the PDT of cancer.

  13. 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.

  14. 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.

  15. Phototherapy, photodynamic therapy and lasers in the treatment of acne.

    Science.gov (United States)

    Degitz, Klaus

    2009-12-01

    Modern acne therapy uses anticomedogenic, antimicrobial, antiinflammatory,and antiandrogenic substances. As an additional approach in recent years, treatments have been developed based on the application of electromagnetic radiation. Visible light or infrared wave lengths are utilized by most techniques, including blue light lamps, intense pulsed light, photodynamic therapy and lasers. This review evaluates the various methods with regard to efficacy and their current role in the management of acne. Although UV radiation has been frequently used to treat acne, it is now regarded as obsolete due to the unfavorable risk-benefit ratio. Visible light, especially of blue wavelengths, appears to be suitable for the treatment of mild to moderate inflammatory acne. Photodynamic therapy is effective, but, due to considerable immediate side effects, it is best reserved for selected situations. Despite promising observations, intense pulsed light and lasers have to be evaluated in further studies, before they can be recommended.

  16. Responses of Cancer Cells Induced by Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Toshihiro Kushibiki

    2013-01-01

    Full Text Available Photodynamic therapy (PDT involves the administration of a photosensitizer, followed by local irradiation of tumor tissues using a laser of an appropriate wavelength to activate the photosensitizer. Since multiple cellular signaling cascades are concomitantly activated in cancer cells exposed to the photodynamic effect, understanding the responses of cancer cells to PDT will aid in the development of new interventions. This review describes the possible cell-death signaling pathways initiated by PDT. In addition, we describe our latest findings regarding the induction of expression of miRNAs specific to apoptosis in cancer cells and the induction of antitumor immunity following PDT against cancer cells. A more detailed understanding of the molecular mechanisms related to PDT will potentially improve long-term survival of PDT treated patients.

  17. 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.

  18. In vivo uptake and photodynamic activity of porphycenes

    Science.gov (United States)

    Kimel, Sol; Gottfried, Varda; Davidi, Ronit; Averbuj, Claudia

    1994-03-01

    Novel porphyrinoid photosensitizers are currently being considered for use in photodynamic therapy (PDT) of cancer. This class of sensitizers combines high absorption characteristics at the therapeutic wavelengths ((lambda) > 600 nm) and good tumor targeting properties. We have investigated the in-vivo uptake and photodynamic damage of several porphycenes. Our model system was the chick chorioallantoic membrane (CAM) which we have adapted for use in PDT studies. The CAM assay allows fast screening of novel drugs and obtaining statistically relevant results with minute quantities of the drug. Sensitizers were `trapped' in EPC (egg phosphatidylcholine) or in DPPC (dipalmitoyl phosphatidylcholine); their efficiencies were independent of the vehicle used for application of the sensitizer. The efficiencies of various porphycenes in PDT, as a function of drug and light dose, compare well with those of standard porphyrins and phthalocyanines.

  19. 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.

  20. 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.

  1. Routine experimental system for defining conditions used in photodynamic therapy and fluorescence photodetection of (non-) neoplastic epithelia

    Science.gov (United States)

    Lange, Norbert; Vaucher, Laurent; Marti, Alexandre; Etter, Anne-Lise; Gerber, Patrick; van den Bergh, Hubert; Jichlinski, Patrice; Kucera, Pavel

    2001-04-01

    A common method to induce enhanced short-term endogenous porphyrin synthesis and accumulation in cell is the topical, systemic application of 5-aminolevulinic acid or one of its derivatives. This circumvents the intravenous administration of photosensitizers normally used for photodynamic therapy (PDT) of fluorescence photodetection. However, in the majority of potential medical indications, optimal conditions with respect to the porphyrin precursor or its pharmaceutical formulation have not yet been found. Due to ethical restrictions and animal right directives, the number of available test objects is limited. Hence, definition and use of nonanimal test methods are needed. Tissue and organ cultures are a promising approach in replacing cost intensive animal models in early stages of drug development. In this paper, we present a tissue culture, which can among others be used routinely to answer specific questions emerging in the field of photodynamic therapy and fluorescence photodetection. This technique uses mucosae excised from sheep paranasal sinuses or pig bladder, which is cultured under controlled conditions. It allows quasiquantative testing of different protoporphyrin IX precursors with respect to dose-response curves and pharmacokinetics, as well as the evaluation of different incubation conditions and/or different drug formulations. Furthermore, this approach, when combined with the use of electron microscopy and fluorescence-based methods, can be used to quantitatively determine the therapeutic outcome following protoporphyrin IX-mediated PDT.

  2. Gold nanoparticles enhance methylene blue-induced photodynamic therapy: a novel therapeutic approach to inhibit Candida albicans biofilm.

    Science.gov (United States)

    Khan, Shakir; Alam, Fahad; Azam, Ameer; Khan, Asad U

    2012-01-01

    This article explores the novel gold nanoparticle-enhanced photodynamic therapy of methylene blue against recalcitrant pathogenic Candida albicans biofilm. Physiochemical (X-ray diffraction, ultraviolet-visible absorption, photon cross-correlation, FTIR, and fluorescence spectroscopy) and electron microscopy techniques were used to characterize gold nanoparticles as well as gold nanoparticle-methylene blue conjugate. A 38.2-J/cm(2) energy density of 660-nm diode laser was applied for activation of gold nanoparticle-methylene blue conjugate and methylene blue against C. albicans biofilm and cells. Antibiofilm assays, confocal laser scanning, and electron microscopy were used to investigate the effects of the conjugate. Physical characteristics of the gold nanoparticles (21 ± 2.5 nm and 0.2 mg/mL) and methylene blue (20 μg/mL) conjugation were confirmed by physicochemical and electron microscopy techniques. Antibiofilm assays and microscopic studies showed significant reduction of biofilm and adverse effect against Candida cells in the presence of conjugate. Fluorescence spectroscopic study confirmed type I photo toxicity against biofilm. Gold nanoparticle conjugate-mediated photodynamic therapy may be used against nosocomially acquired refractory Candida albicans biofilm.

  3. Modulation of tumor response to photodynamic therapy in severe combined immunodeficient (SCID) mice by adoptively transferred lymphoid cells

    Science.gov (United States)

    Korbelik, Mladen; Krosl, Gorazd; Krosl, Jana; Dougherty, Graeme J.

    1996-04-01

    Photodynamic treatment, consisting of intravenous injection of PhotofrinR (10 mg/kg) followed by exposure to 110 J/cm2 of 630 plus or minus 10 nm light 24 hours later, cured 100% of EMT6 tumors (murine mammary sarcoma) growing in syngeneic immunocompetent BALB/C mice. In contrast, the same treatment produced no cures of EMT6 tumors growing in either nude or SCID mice (immunodeficient strains). EMT6 tumors growing in BALB/C and SCID mice showed no difference in either the level of PhotofrinR accumulated per gram of tumor tissue, or the extent of tumor cell killing during the first 24 hours post photodynamic therapy (PDT). In an attempt to improve the sensitivity to PDT of EMT6 tumors growing in SCID mice, these hosts were given either splenic T lymphocytes or whole bone marrow from BALB/C mice. The adoptive transfer of lymphocytes 9 days before PDT was successful in delaying tumor recurrence but produced no cures. A better improvement in PDT response was obtained with tumors growing in SCID mice reconstituted with BALB/C bone marrow (tumor cure rate of 63%). The results of this study demonstrate that, at least with the EMT6 tumor model, antitumor immune activity mediated by lymphoid cell populations makes an important contribution to the curative effect of PDT.

  4. 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.

  5. 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.

  6. Photodynamic action on some pathogenic microorganisms of oral cavity

    Science.gov (United States)

    Ovchinnikov, Ilya S.; Tuchin, Valery V.

    2001-10-01

    The work is devoted to an analysis of pre-clinical and clinical experiments on photodynamic action of HeNe laser radiation in aggregate with a cation thiazinium dye Methylene Blue (MB) on a mix of pathogenic and conditionally pathogenic aerobic bacteria being activators of pyoinflammatory diseases of oral cavity. Concentration of photosensitizes at which there is no own bactericidal influence on dying microflora, and parameters of influence at which the efficiency of irradiated microflora defeat reaches 99 % are determined.

  7. Improvement of photodynamic activity of aluminium sulphophthalocyanine due to biotinylation

    Science.gov (United States)

    Meerovich, Irina G.; Jerdeva, Victoria V.; Derkacheva, Valentina M.; Meerovich, Gennadii A.; Lukyanets, Eugeny A.; Kogan, Eugenia A.; Savitsky, Alexander P.

    2003-09-01

    The photodynamic activity of dibiotinylated aluminium sulphophthalocyanine in vitro and in vivo were studied. It was obtained that in vitro dibiotinylated aluminium sulphophthalocyanine provides the effective damage of small cell lung carcinoma OAT-75. In vivo dibiotinylated aluminium sulphophthalocyanine causes destruction of tumor (Erlich carcinoma), results in total necrosis of tumor tissue and expresses vascular damage (trombosis and destruction of vascular walls) even in concentration 0.25 mg/kg of a body weight.

  8. Main stages of development of photodynamic therapy in Russia

    Directory of Open Access Journals (Sweden)

    E. F. Stranadko

    2015-01-01

    Full Text Available The main stages of development and establishment of photodynamic therapy (PDT in Russia are described in the article. Brief description of photosensitizers approved for clinical use in Russia including fotogem, photosens, alasens, radachlorine and fotoditazin is represented. Their physical and chemical and spectral characteristics, drug formulations, results of pre-clinical studies and post-marketing experience are shown. Main research centers dealing with PDT are listed. 

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

    Science.gov (United States)

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

    2016-03-22

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

  10. 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.

  11. Main stages of development of photodynamic therapy in Russia

    OpenAIRE

    E. F. Stranadko

    2015-01-01

    The main stages of development and establishment of photodynamic therapy (PDT) in Russia are described in the article. Brief description of photosensitizers approved for clinical use in Russia including fotogem, photosens, alasens, radachlorine and fotoditazin is represented. Their physical and chemical and spectral characteristics, drug formulations, results of pre-clinical studies and post-marketing experience are shown. Main research centers dealing with PDT are listed. 

  12. 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.

  13. Role of inflammatory cytokines in the response of solid cancers to photodynamic therapy

    Science.gov (United States)

    Korbelik, Mladen; Sun, Jinghai; Cecic, Ivana; Dougherty, Graeme J.

    2001-04-01

    Photodynamic therapy (PDT) elicits a strong acute inflammatory response that has both local and systemic (acute phase response) attributes. The insult mediated by PDT-induced oxidative stress at the targeted site triggers a complex multifactorial response engaging host defence mechanisms associated with the inflammatory process to participate in the eradication of the treated tumor. Inflammatory cytokines are important mediators of critical events in this process as they regulate the activity of inflammatory, endothelial and other cells. The initial stimulus for enhanced production and release of cytokines likely originates from several types of events, such as activated transcription factors and complement deposition. The PDT-induced complement activation appears to be directly linked to the enhanced expression of various cytokines, including chemokines such as KC (in mouse models), and classic inflammatory cytokines such as IL-1β, TNF-α , IL-6 and IL-10. A variety of interventions that modulate the activity of particular cytokines performed in conjunction with PDT were shown to influence the therapy outcome. The treatments such as using blocking antibodies and local or systemic cytokine delivery may either reduce or dramatically improve the curative effect of PDT. The inflammatory and related cytokines that at present appear particularly interesting and merit further investigation for use as adjuvants to PDT are IL-3, IL-8, IL-15, TNF-α, IFN-γ, G-CSF and GM-CSF.

  14. Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

    2005-01-01

    In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

  15. Photodynamic control of human pathogenic parasites in aquatic ecosystems using chlorophyllin and pheophorbid as photodynamic substances.

    Science.gov (United States)

    Wohllebe, S; Richter, R; Richter, P; Häder, D P

    2009-02-01

    When used at low concentrations and added to the water body, water-soluble chlorophyllin (resulting from chlorophyll after removal of the phytol) and pheophorbid (produced from chlorophyllin by acidification) are able to kill mosquito larvae and other small animals within a few hours under exposure of solar radiation. Under laboratory conditions, the use of chlorophyllin/pheophorbid as photodynamic substances for pest control in water bodies promises to be not only effective and ecologically beneficial but also cheap. The LD50 (50% of mortality in the tested organisms) value in Culex sp. larvae was about 6.88 mg/l, in Chaoborus sp. larvae about 24.18 mg/l, and in Daphnia 0.55 mg/l. The LD50 values determined for pheophorbid were 8.44 mg/l in Culex, 1.05 mg/l in Chaoborus, and 0.45 mg/l in Daphnia, respectively. In some cases, chlorophyllin and pheophorbid were also found to be (less) active in darkness. The results presented in this paper show that chlorophyllin is about a factor of 100 more effective than methylene blue or hematoporphyrine, which were tested earlier for the same purpose. It is also much cheaper and, as a substance found in every green plant, it is 100% biodegradable.

  16. 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.

  17. Optimized Photodynamic Therapy with Multifunctional Cobalt Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kyong-Hoon Choi

    2017-06-01

    Full Text Available Photodynamic therapy (PDT has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and determine the influence of light parameters on the photosensitizing agent. In particular, much more knowledge concerning the importance of fluence and exposure time is required to gain a better understanding of the photodynamic efficacy. In the present study, we synthesized novel folic acid-(FA and hematoporphyrin (HP-conjugated multifunctional magnetic nanoparticles (CoFe2O4-HPs-FAs, which were characterized as effective anticancer reagents for PDT, and evaluated the influence of incubation time and light exposure time on the photodynamic anticancer activities of CoFe2O4-HPs-FAs in prostate cancer cells (PC-3 cells. The results indicated that the same fluence at different exposure times resulted in changes in the anticancer activities on PC-3 cells as well as in reactive oxygen species formation. In addition, an increase of the fluence showed an improvement for cell photo-inactivation. Therefore, we have established optimized conditions for new multifunctional magnetic nanoparticles with direct application for improving PDT for cancer patients.

  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. 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.

  1. A basic study of intraoperative photodynamic therapy for lung cancer : photodynamic therapy for lymphogenous metastases in nude rats

    OpenAIRE

    MIZUTANI,Eiki; Inoue, Hidenori; Shimada,Osamu; Matsubara,Hirochika; Kobayashi, Masami; Matsumoto,Masahiko

    2013-01-01

    Background: We designed a new photodynamic therapy (PDT) protocol in which Pheophorbide a (Pba) accumulates in the lymph nodes following local administration around lung cancer tumors, followed by lobectomy and irradiation of the lymph nodes with lasers. As the fi rst step, we evaluated whether administering PDT for metastatic lymph nodes is possible in a rat model.Materials and Methods: Human lung squamous cell carcinoma (RERF-LC-AI) cells were subcutaneously injected into the foot pads of n...

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

    Science.gov (United States)

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

    2017-12-01

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

  3. Efficacy of 5-Aminolevulinic Acid Photodynamic Therapy in treatment of nasal inverted papilloma.

    Science.gov (United States)

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao

    2013-12-01

    Evaluate the efficacy of 5-Aminolevulinic Acid Photodynamic Therapy (PDT) in medical treatment of nasal inverted papilloma (NIP). Three patients with nasal inverted papilloma were treated with 5-Aminolevulinic Acid Photodynamic Therapy at our department from April to September 2012. The efficacy and adverse effects of 5-Aminolevulinic Acid Photodynamic Therapy were evaluated during 6-8 months of follow-up medical examination. After treated with 5-Aminolevulinic Acid Photodynamic Therapy, the nasal inverted papillomas were removed. No recurrence was found during the 6-8 months of follow-up medical examination. The major adverse effects were mild erosion, pain, and exudation. 5-Aminolevulinic Acid Photodynamic Therapy appears to be an effective treatment of nasal inverted papilloma. It can clear the papilloma lesions and is well tolerated by the patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Internal heavy atom effect of Au(III) and Pt(IV) on hypocrellin A for enhanced in vitro photodynamic therapy of cancer.

    Science.gov (United States)

    Zhou, Lin; Ge, Xuefeng; Liu, Jihua; Zhou, Jiahong; Wei, Shaohua; Li, Fuyou; Shen, Jian

    2013-10-01

    Hypocrellin A (HA), an a natural perylene quinine photosensitizers (PSs), can chelate with heavy metal ions, including Au(III) and Pt(IV), to form a 1:2 complex, which exhibits enhanced (1)O2 generation quantum yield through the increased intersystem crossing efficiency mediated by internal heavy atom effect. Besides, the chelate process greatly improved the water solubility of HA. Comparative studies with HA and complexes have demonstrated that the heavy-atom effect on HA molecules enhances the efficiency of in vitro photodynamic (PDT) efficacy.

  5. Photodynamic inactivation of microorganisms present on complete dentures. A clinical investigation. Photodynamic disinfection of complete dentures.

    Science.gov (United States)

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

    2012-01-01

    The aim of this study was to evaluate the effectiveness of photodynamic therapy (PDT) for the disinfection of complete dentures. Biofilm samples were collected from dentures of 60 denture users who were randomly divided into four experimental groups (n = 15 each): subjects whose maxillary dentures were sprayed with 50 and 100 mg/l of Photogem® suspension (groups P50S and P100S) and patients whose maxillary dentures were treated with 50 and 100 mg/l of Photogem® gel (groups P50G and P100G). Dentures with photosensitizers were left in the dark for 30 min (pre-irradiation time) and then irradiated with blue LED light at 37.5 J/cm(2) (26 min). Denture samples were taken with sterile cotton swab before (left side surfaces) and after (right side surfaces) PDT. All microbial material was diluted and plated on selective media for Candida spp., Staphylococcus mutans spp., streptococci and a non-selective media. After incubation (48 h/37°C), the number of colony-forming units (cfu/ml) was counted. Microorganisms grown on selective media were identified using biochemical methods before and after PDT. The data were submitted to McNemar and Kruskal-Wallis tests (α = 0.05). No growth after PDT was observed in 60, 53, 47, and 40% of dentures from P100G, P50G, P100S, and P50S groups, respectively. When evidence of microorganisms' growth was observed, PDT regimens eliminated over 90% of microorganisms on dentures. This clinical study showed that PDT was effective for disinfecting dentures.

  6. Influence of CaNa2 EDTA on topical 5-aminolaevulinic acid photodynamic therapy

    Institute of Scientific and Technical Information of China (English)

    刘辉峰; 徐世正; 张春荣

    2004-01-01

    Background We asssessed whether the CaNa2 EDTA could improve the accumulation of protoporphyrin Ⅸ (PpⅨ) and photosensitisation in HEp-2 cells as well as the depth of treatment of skin cancers on the topical 5-Aminolaevulinic acid (5-ALA) PDT.Methods HEp-2 cells were incubated with 5-ALA (0-1mmol/L) and CaNa2EDTA (0-1mmol/L) for 4 hours, intracellular protoporphyrin Ⅸ content was quantified by extraction, and cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light. In comparison with the pictures before and after treatment, depth of treatment could be determined using a Acuson Sequioa 512 phase-array system in paired experiments.Results PpⅨ accumulation increased with increasing extracellular concentrations of ALA (0-1mmol/L). Adding 1mmol/L of CaNa2EDTA increased 30% PpⅨ accumulation over the same period of incubation in the concentration of 1mmol/L ALA. Significant difference was observed between the 5-ALA alone group and 5-ALA combined CaNa2 EDTA group in the PpⅨ accumulation (P<0.01). Cell viability after exposure to light decreased with adding CaNa2 EDTA, a statistical difference in a same fluence above 1.2 J/cm2 between two groups was demonstrated (P<0.05, P<0.01 respectively). Depth of treatment of skin cancers were increased in CaNa2 EDTA-treated group.conclusion CaNa2 EDTA could improve the PpⅨ accumulation and photosensitisation in HEp-2 cells. Clinically, CaNa2 EDTA could increase the depth of treatment in the cutaneous cancers.

  7. The Effect of HMME-Mediated Photodynamic Therapy on Streptococcus Mutans of Cariogenic Bacteria and Caries Morphology%血卟啉单甲醚光动力疗法对致龋变形链球菌及龋损表面形态的影响

    Institute of Scientific and Technical Information of China (English)

    李敏; 邹朝晖; 张蕾; 马莹莹; 阴慧娟

    2011-01-01

    目的:探讨以血卟啉单醚(HMME)为光敏剂的光动力疗法(PDT)在龋病预防中的作用.方法:采用变形链球菌接种Wistar大鼠磨牙,给予致龋饲料,建立龋病模型.将大鼠分为5组,分别用10 ng/L HMME-PDT(A组)、20ng/L HMME-PDT(B组)、40 ng/L HMME-PDT(C组)、0.2 g/L氟化钠水溶液(D组)和生理盐水(E组)处理各组大鼠磨牙,每周1次,连续4周,记录大鼠口腔变形链球菌生长情况.处死大鼠后用扫描电镜观察各组磨牙龋损区的表面形态.结果:第1周和第2周各组菌落数差异均无统计学意义(P>0.05),第3周B组、C组菌落数低于E组,C组低于D组.(P<0.05).第4周A组、B组和C组菌落数均低于E组(P<0.05或P<0.01),C组菌落数低于A组、B组和D组(P<0.05),扫描电镜观察发现C组与D组龋损破坏程度最轻且表面相对平滑.结论:PDT具有抑制龋病的作用,将为龋病的预防提供一种新的有效途径.%Objective: To study the role of photodynamic therapy (PDT) using hematoporphyrin monomethyl ether (HMME) as photosensitizer in the prevention of dental caries by establishing the caries of rat model. Methods: The molars of Wistar rats were inoculated with Streptococcus mutans (S. mutans). Rats were fed with caries - inducing diet to establish the rat model of caries. Rats were divided into five groups. Molars of rats were treated with 10 ng/L HMME-PDT (group A), 20 ng/L HMME-PDT (group B), 40 ng/L HMME-PDT (group C), 0.2 g/L sodium fluoride as positive control (group D) and 0.9% sterile physiological saline as negative control (group E) once a week for four weeks. The changes of S. mutans were recorded every week. The rats were then killed. The surface morphology of dental caries of rats was observed by scanning electron microscope. Results: The colony count in each group were no significant difference in the first and second weeks (P > 0.05). The colony counts were significantly reduced in group B and C compared with those of group E in the third

  8. 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.

  9. Successful treatment of oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy--report of 3 cases.

    Science.gov (United States)

    Chang, Yu-Chao; Yu, Chuan-Hang

    2014-06-01

    Our previous study showed successful treatment of a large oral verrucous hyperplasia (OVH) with topical 5-aminolevulinic acid-mediated photodynamic therapy combined with cryotherapy (ALA-PDT). In this case series, we extended this combined method for another three OVH lesions in three different patients. The clinical procedure was conducted as follows: the OVH lesions were irradiated with a 635-nm laser 1.5h after topical application of 20% ALA on the lesion for a total of 1000 s, which consisted of five 3-min and one 100-s irradiations separated by five 3-min rests. Cryogun cryotherapy was then performed on the lesion after ALA-PDT. The tumor was cleared after 1-6 treatments. No recurrence of the lesion was found after a follow-up period of 6-24 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    Science.gov (United States)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2011-03-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  11. Effect of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells.

    Science.gov (United States)

    Jiang, Yuan; Leung, Albert Wingnang; Wang, Xinna; Zhang, Hongwei; Xu, Chuanshan

    2014-07-01

    In the present study, we investigated effects of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells in vitro. Human ovarian cancer HO-8910 cell as a cancer model cell was incubated with hypocrellin B at a concentration of 2.5 μM for 5 h and irradiated by light from a light-emitting diodes (LED) source. Cell apoptosis was analyzed by flow cytometry with annexin V/propidium iodide (PI) staining and nuclear staining 6 h after hypocrellin B photoirradiation. Cell adhesion was assessed using the 3-(4, 5-dimthylthiazol-2-yl)-2, 5 diphenyl-tetrazolium bromide (MTT) assay 4 h after photodynamic treatment. Cell migration was measured 48 h after photodynamic treatment. Flow cytometry with annexin V/PI staining showed that early apoptotic and late apoptotic (necrotic) rates following photodynamic therapy with hypocrellin B markedly increased to 16.40% and 24.67%, respectively. Nuclear staining found nuclear condensation and typical apoptotic body in the treated cells. The number of cell migration was significantly decreased to 183 ± 28 after photodynamic therapy with hypocrellin B (p photodynamic action of hypocrellin B was 53.2 ± 1.8%, significantly higher than 2.7 ± 2.1% of light treatment alone and 1.0 ± 0.4% of hypocrellin B treatment alone (p photodynamic therapy with hypocrellin B remarkably induced apoptosis and inhibited adhesion and migration of cancer cells in vitro.

  12. Efficient photodynamic therapy on human retinoblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Jan Walther

    Full Text Available Photodynamic therapy (PDT has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma.

  13. Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

    Science.gov (United States)

    Walther, Jan; Schastak, Stanislas; Dukic-Stefanovic, Sladjana; Wiedemann, Peter; Neuhaus, Jochen; Claudepierre, Thomas

    2014-01-01

    Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma. PMID:24498108

  14. 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.

  15. Fast and effective: intense pulse light photodynamic inactivation of bacteria.

    Science.gov (United States)

    Maisch, Tim; Spannberger, Franz; Regensburger, Johannes; Felgenträger, Ariane; Bäumler, Wolfgang

    2012-07-01

    The goal of this study was to investigate the photodynamic toxicity of TMPyP (5, 10, 15, 20-Tetrakis (1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate) in combination with short pulses (ms) of an intense pulse light source within 10 s against Bacillus atrophaeus, Staphylococcus aureus, Methicillin-resistant S. aureus and Escherichia coli, major pathogens in food industry and in health care, respectively. Bacteria were incubated with a photoactive dye (TMPyP) that is subsequently irradiated with visible light flashes of 100 ms to induce oxidative damage immediately by generation of reactive oxygen species like singlet oxygen. A photodynamic killing efficacy of up to 6 log(10) (>99.9999%) was achieved within a total treatment time of 10 s using a concentration range of 1-100 μmol TMPyP and multiple light flashes of 100 ms (from 20 J cm(-2) up to 80 J cm(-2)). Both incubation of bacteria with TMPyP alone or application of light flashes only did not have any negative effect on bacteria survival. Here we could demonstrate for the first time that the combination of TMPyP as the respective photosensitizer and a light flash of 100 ms of an intense pulsed light source is enough to generate sufficient amounts of reactive oxygen species to kill these pathogens within a few seconds. Increasing antibiotic resistance requires fast and efficient new approaches to kill bacteria, therefore the photodynamic process seems to be a promising tool for disinfection of horizontal surfaces in industry and clinical purposes where savings in time is a critical point to achieve efficient inactivation of microorganisms.

  16. Adjuvant Intraoperative Photodynamic Therapy in Head and Neck Cancer

    Science.gov (United States)

    Rigual, Nestor R.; Shafirstein, Gal; Frustino, Jennifer; Seshadri, Mukund; Cooper, Michele; Wilding, Gregory; Sullivan, Maureen A.; Henderson, Barbara

    2015-01-01

    IMPORTANCE There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. OBJECTIVES To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. INTERVENTIONS Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. MAIN OUTCOMES AND MEASURES Adverse events and highest laser light dose. RESULTS Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. PMID:23868427

  17. 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.

  18. Photodynamic therapy in colorectal cancer treatment--The state of the art in preclinical research.

    Science.gov (United States)

    Kawczyk-Krupka, Aleksandra; Bugaj, Andrzej M; Latos, Wojciech; Zaremba, Katarzyna; Wawrzyniec, Katarzyna; Kucharzewski, Marek; Sieroń, Aleksander

    2016-03-01

    Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer (CRC). This review aims to give a general overview of preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment to emphasize their potential in study of PDT mechanism, safety and efficiency to translate these results into clinical benefit in CRC treatment. Literature on in vitro preclinical photodynamic studies related to CRC cells and animal studies of photodynamic effects related to CRC treatment with the fallowing medical subject headings search terms: colorectal cancer, photodynamic therapy, photosensitizer(s), in vitro, cell culture(s), in vivo, animal experiment(s). The articles were selected by their relevance to the topic. The majority of preclinical studies concerning possibility of PDT application in colon and rectal cancer is focused on phototoxic action of photosensitizers toward cultured colorectal tumor cells in vitro. The purposes of animal experiments are usually elucidation of mechanisms of observed photodynamic effects in scale of organism, estimation of PDT safety and efficiency and translation of these results into clinical benefit. In vitro photodynamic studies and animal experiments can be useful for studies of mechanisms and efficiency of photodynamic method as a start point on PDT clinical research. The primary disadvantage of in vitro experiments is a risk of over-interpretation of their results during extrapolation to the entire CRC. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. 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.

  20. PHOTODYNAMIC THERAPY: A LIGHT OF HOPE IN FIGHT AGAINST CANCER

    OpenAIRE

    Samanamú Ch., Christian; Pontificia Universidad Católica del Perú,Lima,Perú.; Ninán, Oscar; Pontificia Universidad Católica del Perú; Universidad Nacional Mayor de San Marcos,Lima,Perú.; Santiago C., Julio; Universidad Nacional Mayor de San Marcos; Instituto Peruano de Energía Nuclear,Lima,Perú.

    2014-01-01

    Currently, photodynamic therapy is one of the most promising for the treatment of cancer treatments. This article describes the basic principles of this therapy are explained and a review of the main types of existing photosensitizers currently is performed, with emphasis on those derived from porphyrins and phthalocyanines. En la actualidad, la terapia fotodinámica es uno de los tratamientos más promisorios para el tratamiento del cáncer. En este artículo se explican los principios básico...

  1. Spectroscopic evaluation of photodynamic therapy of the intraperitoneal cavity

    Science.gov (United States)

    Finlay, Jarod C.; Sandell, Julia L.; Zhu, Timothy C.; Lewis, Robert; Cengel, Keith A.; Hahn, Stephen M.

    2015-01-01

    We present the results of spectroscopic measurements of diffuse reflectance and fluorescence before and after photodynamic therapy of healthy canine peritoneal cavity. Animals were treated intra-operatively after iv injection of the benzoporphyrin derivative (BPD). The small bowel was treated using a uniform light field projected by a microlenstipped fiber. The cavity was then filled with scattering medium and the remaining organs were treated using a moving diffuser. Diffuse reflectance and fluorescence measurements were made using a multi-fiber optical probe positioned on the surface of various tissues within the cavity before and after illumination. The measured data were analyzed to quantify hemoglobin concentration and oxygenation and sensitizer concentration. PMID:26028798

  2. Spectroscopic evaluation of photodynamic therapy of the intraperitoneal cavity

    Science.gov (United States)

    Finlay, Jarod C.; Sandell, Julia L.; Zhu, Timothy C.; Lewis, Robert; Cengel, Keith A.; Hahn, Stephen M.

    2010-02-01

    We present the results of spectroscopic measurements of diffuse reflectance and fluorescence before and after photodynamic therapy of healthy canine peritoneal cavity. Animals were treated intra-operatively after iv injection of the benzoporphyrin derivative (BPD). The small bowel was treated using a uniform light field projected by a microlens-tipped fiber. The cavity was then filled with scattering medium and the remaining organs were treated using a moving diffuser. Diffuse reflectance and fluorescence measurements were made using a multi-fiber optical probe positioned on the surface of various tissues within the cavity before and after illumination. The measured data were analyzed to quantify hemoglobin concentration and oxygenation and sensitizer concentration.

  3. In vitro photodynamic inactivation of Sporothrix schenckii complex species.

    Science.gov (United States)

    Nunes Mario, Débora Alves; Denardi, Laura Bedin; Brayer Pereira, Daniela Isabel; Santurio, Janio Morais; Alves, Sydney Hartz

    2014-10-01

    Photodynamic therapy has been applied successfully against cutaneous and subcutaneous mycoses. We applied methylene blue as a photosensitizing agent and light emitting diode (InGaAlP) against Sporothrix schenckii complex species in an in vitro assay. The viability of the conidia was determined by counting colony-forming units. Methylene blue in conjunction with laser irradiation was able to inhibit the growth of all tested samples. The in vitro inhibition of Sporothrix spp. isolates by laser light deserves in vivo experimental and clinical studies since it may be a promising treatment for cutaneous and subcutaneous sporotrichosis.

  4. 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. 

  5. 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...... 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources

    Directory of Open Access Journals (Sweden)

    Catharina M. Lerche

    2016-02-01

    Full Text Available 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.

  11. 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.

  12. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Du, Kevin L; Both, Stefan; Friedberg, Joseph S; Rengan, Ramesh; Hahn, Stephen M; Cengel, Keith A

    2010-09-01

    Intensity modulated radiation therapy (IMRT) has recently been proposed for the treatment of malignant pleural mesothelioma (MPM). Here, we describe our experience with a multimodality approach for the treatment of mesothelioma, incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an intraoperative adjuvant to surgical debulking. The median radiation dose to the planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our series, 1 patient experienced respiratory failure secondary to radiation pneumonitis that did not require mechanical ventilation. Multimodality therapy combining surgery with increased doses of radiation using IMRT, and newer treatment modalities such as PDT , appears safe. Future prospective analysis will be needed to demonstrate efficacy of this approach in the treatment of malignant mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are needed and provide the promise of improved local control and quality of life in a carefully chosen multidisciplinary approach.

  13. [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.

  14. The role of Ca 2+-related signaling in photodynamic injury of nerve and glial cells

    Science.gov (United States)

    Lobanov, A. V.; Petin, Y. O.; Uzdensky, A. B.

    2007-05-01

    Photodynamic therapy (PDT) inhibited and irreversibly abolished firing, caused necrosis of neurons, necrosis, apoptosis and proliferation of glial cells in the isolated crayfish stretch receptor. The role in these processes of the central components of Ca 2+-mediated signaling pathway: phospholipase C, calmodulin, calmodulin-dependent kinase II, and protein kinase C was studied using their inhibitors: ET-18, fluphenazine, KN-93, or staurosporine, respectively. ET-18 reduced functional inactivation of neurons, necrosis and apoptosis of glial cells. Fluphenazine and KN-93 reduced PDT-induced necrosis of neurons and glial cells. Staurosporine enhanced PDT-induced glial apoptosis. PDTinduced gliosis was prevented by KN-93 and staurosporine. Therefore, phospholipase C participated in neuron inactivation and glial necrosis and apoptosis. Calmodulin and calmodulin-dependent kinase II were involved in PDT-induced necrosis of neurons and glial cells but not in glial apoptosis. Protein kinase C protected glia from apoptosis and participated in PDT-induced gliosis and loss of neuronal activity. These data may be used for modulation of PDT of brain tumors.

  15. 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.

  16. MoO3-x quantum dots for photoacoustic imaging guided photothermal/photodynamic cancer treatment.

    Science.gov (United States)

    Ding, Dandan; Guo, Wei; Guo, Chongshen; Sun, Jianzhe; Zheng, Nannan; Wang, Fei; Yan, Mei; Liu, Shaoqin

    2017-02-02

    A theranostic system of image-guided phototherapy is considered as a potential technique for cancer treatment because of the ability to integrate diagnostics and therapies together, thus enhancing accuracy and visualization during the treatment. In this work, we realized photoacoustic (PA) imaging-guided photothermal (PT)/photodynamic (PD) combined cancer treatment just via a single material, MoO3-x quantum dots (QDs). Due to their strong NIR harvesting ability, MoO3-x QDs can convert incident light into hyperthermia and sensitize the formation of singlet oxygen synchronously as evidenced by in vitro assay, hence, they can behave as both PT and PD agents effectively and act as a "dual-punch" to cancer cells. In a further study, elimination of solid tumors from HeLa-tumor bearing mice could be achieved in a MoO3-x QD mediated phototherapeutic group without obvious lesions to the major organs. In addition, the desired PT effect also makes MoO3-x QDs an exogenous PA contrast agent for in vivo live-imaging to depict tumors. Compared with previously reported theranostic systems that put several components into one system, our multifunctional agent of MoO3-x QDs is exempt from unpredictable mutual interference between components and ease of leakage of virtual components from the composited system.

  17. 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.

  18. Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.

    Science.gov (United States)

    Weijer, Ruud; Clavier, Séverine; Zaal, Esther A; Pijls, Maud M E; van Kooten, Robert T; Vermaas, Klaas; Leen, René; Jongejan, Aldo; Moerland, Perry D; van Kampen, Antoine H C; van Kuilenburg, André B P; Berkers, Celia R; Lemeer, Simone; Heger, Michal

    2017-03-01

    Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). The post-PDT survival pathways and metabolism were studied following sublethal (LC50) and supralethal (LC90) PDT. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly HIF-1-, NF-кB-, AP-1-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. PDT-subjected SK-ChA-1 cells downregulated proteins associated with EGFR signaling, particularly at LC90. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor-associated cell types that transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, tumor cells sublethally afflicted by PDT are a major therapeutic culprit. Our multi-omic analysis further unveiled multiple druggable targets for pharmacological co-intervention.

  19. 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.

  20. 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.

  1. Topical photodynamic therapy of squamous cell carcinomas in a hairless mouse model

    Science.gov (United States)

    Wang, Hong-Wei; Lv, Ting; Li, Jing-Jing; Tu, Qingfeng; Huang, Zheng; Wang, Xiu-Li

    2013-02-01

    Objectives: To examine therapeutic effects of 5-aminolevulinate (ALA)-mediated photodynamic therapy (PDT) on UVB-induced cutaneous squamous cell carcinomas (SCCs) in a mouse model. Materials and methods: Cutaneous SCCs were established by UVB (280-320 nm) irradiation of hairless mice. In situ fluorescence measurement was used to monitor PpIX formation after the topical application of various concentrations of ALA cream to determine the optimal ALA dose. Therapeutic responses of SCCs to multiple sessions of ALA PDT were examined histologically and quantitatively. TUNEL staining was used to examine apoptosis caused by PDT. Results: After repeated exposure for 18 to 22 weeks (4-5 days/week), multiple nodular and verrucous hyperplasia lesions of various sizes developed at the exposed area. After four sessions of ALA PDT (8% ALA, 3 h incubation, 30 J/cm2 at 20 mW/cm2) a total of 84% of complete response was achieved for small SCCs (1-4 mm, thickness <2.5 mm). TUNEL staining showed that PDT-induced apoptotic cells were distributed evenly from the basal to stratum corneum layers. Conclusions: Topical ALA PDT can trigger apoptosis in SCCs, inhibit SCC growth, and reduce the size and number of tumors in the hairless mouse model. The true clinical value of ALA PDT for the treatment of cutaneous SCC deserves further investigation.

  2. Apoptosis of gastric cancer cell line MKN45 by photodynamic treatment with photofrin.

    Science.gov (United States)

    Takahira, Kenichiro; Sano, Munetaka; Arai, Hajime; Hanai, Hiroyuki

    2004-01-01

    The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the gastric cancer cell line MKN45 with focus on the mechanism of apoptosis. Gastric cancer cells (MKN45) were incubated with Photofrin for up to 24 h before exposure to He-Cd laser (441 nm, 1 J/cm2). Cell viability was assessed by the methyl-tetra-zolium assay after exposure to light. A 95% cell death (LD95) was measured with 10 microg/ml of Photofrin. DNA ladder formation and chromatin condensation were seen within 60 min. Caspase-3-like and caspase-9-like activities increased from 15 min after exposure to light. Reduction of rhodamine 123 uptake started at 30 min. Caspase-inhibitor VAD-fmk (10 mM) inhibited apoptosis, but did not influence cell viability. In conclusion, Photofrin-mediated PDT in the gastric cancer cell line MKN45 induces apoptosis within 60 min, and mitochondrial damage is likely as the first event of apoptosis.

  3. 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.

  4. Two-photon photodynamic properties of TBO-AuNR-in-shell nanoparticles (Conference Presentation)

    Science.gov (United States)

    Wu, Cheng-Han; Yeh, Chen-Sheng; Cheng, Fong-Yu; Tsai, Zen-Uong; Liu, Tzu-Ming

    2016-03-01

    Photodynamic therapy (PDT) is a light-activated chemotherapeutic treatment that utilizes singlet oxygen and reactive oxygen species induced oxidative reactions to react with surrounding biological substrates, which either kills or irreversibly damages malignant cells. We used multiphoton nonlinear optical microscopy to observe the photo-dynamic effects of TBO-AuNR-in-shell NPs. Excited by femtosecond Cr:forsterite laser operating at 1230nm, singlet oxygen were generated through a plasmon-enhanced two-photon nonlinear optical process. For cells took up NPs, this photodynamic effect can kill the cell. From nonlinear optical microscopy images, we found they shrunk after 3 minutes of illumination.

  5. Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer.

    Science.gov (United States)

    Zhang, Shaojuan; Yang, Ling; Ling, Xiaoxi; Shao, Pin; Wang, Xiaolei; Edwards, W Barry; Bai, Mingfeng

    2015-12-01

    Photodynamic therapy (PDT) has been proven to be a minimally invasive and effective therapeutic strategy for cancer treatment. It can be used alone or as a complement to conventional cancer treatments, such as surgical debulking and chemotherapy. The mitochondrion is an attractive target for developing novel PDT agents, as it produces energy for cells and regulates apoptosis. Current strategy of mitochondria targeting is mainly focused on utilizing cationic photosensitizers that bind to the negatively charged mitochondria membrane. However, such an approach is lack of selectivity of tumor cells. To minimize the damage on healthy tissues and improve therapeutic efficacy, an alternative targeting strategy with high tumor specificity is in critical need. Herein, we report a tumor mitochondria-specific PDT agent, IR700DX-6T, which targets the 18kDa mitochondrial translocator protein (TSPO). IR700DX-6T induced apoptotic cell death in TSPO-positive breast cancer cells (MDA-MB-231) but not TSPO-negative breast cancer cells (MCF-7). In vivo PDT study suggested that IR700DX-6T-mediated PDT significantly inhibited the growth of MDA-MB-231 tumors in a target-specific manner. These combined data suggest that this new TSPO-targeted photosensitizer has great potential in cancer treatment. Photodynamic therapy (PDT) is an effective and minimally invasive therapeutic technique for treating cancers. Mitochondrion is an attractive target for developing novel PDT agents, as it produces energy to cells and regulates apoptosis. Current mitochondria targeted photosensitizers (PSs) are based on cationic molecules, which interact with the negatively charged mitochondria membrane. However, such PSs are not specific for cancerous cells, which may result in unwanted side effects. In this study, we developed a tumor mitochondria-targeted PS, IR700DX-6T, which binds to translocator protein (TSPO). This agent effectively induced apoptosis in TSPO-positive cancer cells and significantly

  6. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity.

    Science.gov (United States)

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-02-23

    The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer-methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  7. Treatment of spontaneously occurring veterinary tumors with photodynamic therapy

    Science.gov (United States)

    Panjehpour, Masoud; Legendre, Alfred; Sneed, Rick E.; Overholt, Bergein F.

    1992-06-01

    Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and/or a cylindrical diffuser. The light dose was 100 J/cm2 superficially or 300 J/cm interstitially. Eleven photodynamic therapy treatments in seven cats and one dog were performed. Two cats received a second treatment in approximately sixty days after the initial treatment. The superficial dose of light was increased to 200 J/cm2 for the second treatment. While the longest follow-up is twelve months, the responses are encouraging. The dog had a complete response. Among the cats, three showed complete response, three showed partial response and one showed no response. One cat expired two days post treatment. It is early to evaluate the response in two cats that received second treatments. Photodynamic therapy with chloroaluminum phthalocyanine tetrasulfonate was effective in treating squamous cell carcinoma in pet animals.

  8. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

    Directory of Open Access Journals (Sweden)

    Monika Dabrzalska

    2017-02-01

    Full Text Available The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB. As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  9. Photodynamic inactivation of contaminated blood with Staphylococcus aureus

    Science.gov (United States)

    Corrêa, Thaila Q.; Inada, Natalia M.; Pratavieira, Sebastião.; Blanco, Kate C.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-03-01

    The presence of bacteria in the bloodstream can trigger a serious systemic inflammation and lead to sepsis that cause septic shock and death. Studies have shown an increase in the incidence of sepsis over the years and it is mainly due to the increased resistance of microorganisms to antibiotics, since these drugs are still sold and used improperly. The bacterial contamination of blood is also a risk to blood transfusions. Thus, bacteria inactivation in blood is being studied in order to increase the security of the blood supply. The purpose of this study was to decontaminate the blood using the photodynamic inactivation (PDI). Human blood samples in the presence of Photogem® were illuminated at an intensity of 30 mW/cm2, and light doses of 10 and 15 J/cm2. Blood counts were carried out for the quantitative evaluation and blood smears were prepared for qualitative and morphological evaluation by microscopy. The results showed normal viability values for the blood cells analyzed. The light doses showed minimal morphological changes in the membrane of red blood cells, but the irradiation in the presence of the photosensitizer caused hemolysis in red blood cells at the higher concentrations of the photosensitizer. Experiments with Staphylococcus aureus, one of the responsible of sepsis, showed 7 logs10 of photodynamic inactivation with 50 μg/mL and 15 J/cm2 and 1 log10 of this microorganism in a co-culture with blood.

  10. Pulmonary decontamination for photodynamic inactivation with extracorporeal illumination

    Science.gov (United States)

    Geralde, Mariana C.; Leite, Ilaiáli S.; Inada, Natalia M.; Grecco, Clóvis; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Infectious pneumonia is a major cause of morbidity and mortality, despite advances in diagnostics and therapeutics in pulmonary infections. One of the major difficulties associated with the infection comes from the high rate of antibiotic resistant microorganisms, claiming for the use of alternative techniques with high efficiency and low cost. The photodynamic inactivation (PDI) is emerging as one of the great possibilities in this area, once its action is oxidative, not allowing microorganism develops resistance against the treatment. PDI for decontamination pulmonary has potential for treatment or creating better conditions for the action of antibiotics. In this study, we are developing a device to implement PDI for the treatment of lung diseases with extracorporeal illumination. To validate our theory, we performed measurements in liquid phantom to simulate light penetration in biological tissues at various fluency rates, the temperature was monitored in a body of hairless mice and the measurements of light transmittance in this same animal model. A diode laser emitting at 810 nm in continuous mode was used. Our results show 70% of leakage at 0.5 mm of thickness in phantom model. The mouse body temperature variation was 5.4 °C and was observed light transmittance through its chest. These results are suggesting the possible application of the extracorporeal illumination using infrared light source. Based on these findings, further studies about photodynamic inactivation will be performed in animal model using indocyanine green and bacteriochlorin as photosensitizers. The pulmonary infection will be induced with Streptococcus pneumoniae and Klebsiella pneumoniae.

  11. Photodynamic research at Baylor University Medical Center Dallas, Texas

    Science.gov (United States)

    Gulliya, Kirpal S.; Matthews, James Lester; Sogandares-Bernal, Franklin M.; Aronoff, Billie L.; Judy, Millard M.

    1993-03-01

    We received our first CO2 laser at Baylor University Medical Center in December 1974, following a trip to Israel in January of that year. Discussion with the customs office of the propriety of charging an 18% import tax lasted for nine months. We lost that argument. Baylor has been using lasers of many types for many procedures since that time. About ten years ago, through the kindness of Tom Dougherty and Roswell Park, we started working with photodynamic therapy, first with hematoporphyrin I and later with dihematoporphyrin ether (II). In February 1984, we were invited to a conference at Los Alamos, New Mexico, U.S.A. on medical applications of the free electron laser as part of the Star Wars Program. A grant application from Baylor was approved that November, but funding did not start for many months. This funding contributed to the development of a new research center as part of Baylor Research Institute. Many of the projects investigated at Baylor dealt with applications of the free electron laser (FEL), after it became available. A staff was assembled and many projects are still ongoing. I would like to outline those which are in some way related to photodynamic therapy.

  12. Applications of photothermic methods in photodynamic therapy investigations

    Science.gov (United States)

    Frąckowiak, D.; Dudkowiak, A.; Wiktorowicz, K.

    2003-06-01

    The applications of steady state photoacoustic and time resolved photothermal methods are carried out in our laboratory. Based on these methods, the selection of optimal sensitizers for photodynamic therapy and photodynamic diagnosis of cancer were described. Additionally, in order to establish the fate of absorbed energy, the absorption and fluorescence spectra were measured. All spectra were measure using natural and/or linearly polarized light because of polarized spectroscopy delivers information about the sample structures. Spectral and photochemical properties of selected sensitizers (merocyanines, porphyrines and phthalocyanines) were investigated. All dyes were first investigated in model systems (fluid solutions or rigid matrix) and later incorporated into resting or stimulated cells as well as into cancer cells delivered from cell lines. Stimulated cells could serve as models of malignant tissue and the properties of these cells at various procedures of stimulation were compared. It was shown that steady state photoacoustic, which is less perturbed by scattering than absorption, is very useful in the establishment of the efficiency of sensitizer incorporation into cells whereas a time resolved photothermal method (laser induced optoacoustic spectroscopy) enabled the establishment of a yield of dye triplet states generation. The triplet states are very active in photochemical reactions. Therefore, on the basis of their yield, it is possible to predict the efficiency of light induced lesions of malignant cells.

  13. Direct phosphorescent detection of primary event of photodynamic action

    Science.gov (United States)

    Losev, Anatoly P.; Knukshto, Valentin N.; Zhuravkin, Ivan N.

    1994-07-01

    Highly phosphorescent photosensitizer Pd-tetra (o-methoxy-p-sulfo) phenyl porphyrin (Pd-MSPP) was used to follow the primary events of photodynamic action - quenching of triplet states by free oxygen in different systems: water solutions of proteins, cells and tissues in vivo and in vitro. The photosensitizer forms complexes with proteins in solutions and biosystems showing remarkable hypsochromic shifts of band and an increase of the quantum yield and lifetime of phosphorescence at the binding to proteins. In absence of oxygen the lifetime of phosphorescence is almost single exponential, and depends on the energy of lowest triplet state of the sensitizer. The photochemical quenching of the triplets by cell components is negligible. In presence of free oxygen the quenching of the sensitizer triplets takes place. The emission spectrum of singlet oxygen with maximum 1271 nm was recorded in water protein solutions and quantum yield of sensitized luminescence was measured. In the systems studied, oxygen consumption was detected and oxygen concentration was estimated in the course of photodynamics by an increase in photosensitizer phosphorescence lifetime, using laser flash photolysis technique. At least two exponential kinetics of the phosphorescence decay shows that the distribution of the free oxygen is not uniform in tissues.

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

    Directory of Open Access Journals (Sweden)

    A. L. Akopov

    2015-01-01

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

  15. 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.

  16. Simultaneous two-photon excitation of photodynamic therapy agents

    Science.gov (United States)

    Wachter, Eric A.; Partridge, W. P., Jr.; Fisher, Walter G.; Dees, Craig; Petersen, Mark G.

    1998-07-01

    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 I and type II photodynamic therapy (PDT) agents are examined. In general, while SPE and TPE selection rules may be somewhat different, the excited state photochemical properties are equivalent for both modes of excitation. In vitro promotion of a two-photon photodynamic effect is demonstrated using bacterial and human breast cancer models. These results suggest that use of TPE may be beneficial for PDT, since the technique allows replacement of visible or ultraviolet excitation with non- damaging near infrared light. Further, a comparison of possible excitation sources for TPE indicates that the titanium:sapphire laser is exceptionally well suited for non- linear excitation of PDT agents in biological systems due to its extremely short pulse width and high repetition rate; these features combine to effect efficient PDT activation with minimal potential for non-specific biological damage.

  17. Upconversion nanoparticles for photodynamic therapy and other cancer therapeutics.

    Science.gov (United States)

    Wang, Chao; Cheng, Liang; Liu, Zhuang

    2013-01-01

    Photodynamic therapy (PDT) is a non-invasive treatment modality for a variety of diseases including cancer. PDT based on upconversion nanoparticles (UCNPs) has received much attention in recent years. Under near-infrared (NIR) light excitation, UCNPs are able to emit high-energy visible light, which can activate surrounding photosensitizer (PS) molecules to produce singlet oxygen and kill cancer cells. Owing to the high tissue penetration ability of NIR light, NIR-excited UCNPs can be used to activate PS molecules in much deeper tissues compared to traditional PDT induced by visible or ultraviolet (UV) light. In addition to the application of UCNPs as an energy donor in PDT, via similar mechanisms, they could also be used for the NIR light-triggered drug release or activation of 'caged' imaging or therapeutic molecules. In this review, we will summarize the latest progresses regarding the applications of UCNPs for photodynamic therapy, NIR triggered drug and gene delivery, as well as several other UCNP-based cancer therapeutic approaches. The future prospects and challenges in this emerging field will be also discussed.

  18. Photodynamic therapy in gastrointestinal cancer: a realistic option?

    Science.gov (United States)

    Barr, H

    2000-02-01

    Photodynamic therapy is now a useful and practical option of the local treatment of gastrointestinal cancers. There is increasing screening and surveillance of patients at risk of oesophageal and gastric cancers. The early detection of disease is often unhelpful if an elderly or frail patient needs to be subjected to radical resectional surgery. Photodynamic therapy can eradicate and cure early mucosal disease following a single endoscopic treatment. If the disease is more advanced good local control and palliation is often possible. Overall, palliation can often be achieved using simpler methods which are highly effective and not associated with the problems of prolonged photosensitisation. It is rapidly becoming clear that the ideal indication is for the treatment of dysplastic lesions in the oesophagus associated with columnar-lined oesophagus (Barrett's oesophagus). In these circumstances a heterogeneous field change often with multifocal dysplasia or cancer can be widely eradicated. Similar areas of squamous dysplasia in the upper oesophagus can be treated. At present a major complication of stricture formation is associated with the use of some photosensitisers. The treatment of cancer at the ampulla of Vater and choriocarcinoma is also proving very effective. The treatment can be performed at endoscopy and is well tolerated and safe.

  19. Photodynamic effect of aluminium and zinc tetrasulfophthalocyanines on melanoma cancer cells

    CSIR Research Space (South Africa)

    Maduray, K

    2010-06-01

    Full Text Available Aluminium and zinc tetrasulfophthalocyanines were activated with a 672nm wavelength laser to investigate the photodynamic effects on melanoma cancer, dermal fibroblast and epidermal keratinocyte cells. Aluminium tetrasulfophthalocyanine was more...

  20. Effect of mixed-sulfonated aluminium phthalocyanine on human skin fibroblasts for photodynamic therapy

    CSIR Research Space (South Africa)

    Ndhundhuma, IM

    2008-08-01

    Full Text Available Photodynamic therapy (PDT) can be defined as the combination of a light sensitive drug known as a photosensitizer and visible light of specific wavelength. PDT is carried out by administration of photosensitizer either systemically, locally...

  1. Electrochemical microsensor system for cancer research on photodynamic therapy in vitro

    Science.gov (United States)

    Marzioch, J.; Kieninger, J.; Sandvik, J. A.; Pettersen, E. O.; Peng, Q.; Urban, G.

    2016-10-01

    An electrochemical microsensor system to investigate photodynamic therapy of cancer cells in vitro was developed and applied to monitor the cellular respiration during and after photodynamic therapy. The redox activity and therefore influence of the photodynamic drug on the sensor performance was investigated by electrochemical characterization. It was shown, that appropriate operation conditions avoid cross-sensitivity of the sensors to the drug itself. The presented system features a cell culture chamber equipped with microsensors and a laser source to photodynamically treat the cells while simultaneous monitoring of metabolic parameter in situ. Additionally, the optical setup allows to read back fluorescence signals from the photosensitizer itself or other marker molecules parallel to the microsensor readings.

  2. Implications of photophysical and physicochemical factors on successful application of photodynamic therapy.

    Science.gov (United States)

    Paul, Shubhajit; Heng, Paul Wan Sia; Chan, Lai Wah

    2017-03-06

    Photodynamic therapy is an evolving treatment modality for cancer owing to its non-invasive approach. This mode of therapy depends on the dynamic interaction of light, oxygen and a photoactive drug to induce oxidative damage to affected cells. This apparently simple technique could be complicated by several factors, mainly contributed by the nature of the physicochemical properties of the photoactive drug, variation in light source and exposure time, as well as tumor physiological environment. This review covers a brief history on the use of various fluorophores in photodynamic therapy, successful marketed formulations and the factors affecting the treatment modalities. The potential of nanostructures as effective delivery carriers with improved photodynamic efficacy is also elaborated. A thorough understanding of the chemistry of photoactive drugs, characteristics of the delivery carriers and light irradiation parameters will enable optimal efficacy of photodynamic therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Enhanced photodynamic antitumor effect on gastric cancer by a novel photosensitive stealth liposome.

    Science.gov (United States)

    Namiki, Yoshihisa; Namiki, Tamami; Date, Masataka; Yanagihara, Kazuyoshi; Yashiro, Masakazu; Takahashi, Hiroshi

    2004-07-01

    Lipophilic photosensitizers hold potential for cancer photodynamic therapy. We sought to develop a novel photosensitive stealth liposome (PSSL) which incorporating a lipophilic photosensitizer into its lipid bilayer and to examine its photoactivity. We prepared PSSL composed of lipophilic chlorin e6 (Ce6) ester, dilauroylphosphatidylcholine, dioleoylphosphatidylethanolamine and distearoyl-phosphoethanolamine-N-[poly (ethylene glycol) 2000] and evaluated its photodynamic effect against gastric cancer cell lines and tumor-bearing nude mice models. In gastric cancer cell lines, LC(80) of PSSL was a maximum of 53 times as low as that of Ce6 sodium salt (Ce6-Na). PSSL completely destroyed all tumors in animal models and tumor recurrence levels were minimal (1.5 +/- 0.9%). PSSL achieved greater photodynamic effects in gastric cancer cell lines and in murine models than Ce6-Na. PSSL holds promise for photodynamic therapy for gastric cancer.

  4. Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin.

    Science.gov (United States)

    Huang, Liyi; Szewczyk, Grzegorz; Sarna, Tadeusz; Hamblin, Michael R

    2017-02-23

    It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or fungi. However, the aPDI activity of PF against Gram-negative bacteria is accepted to be extremely low. Here we report that the nontoxic inorganic salt potassium iodide (KI) at a concentration of 100 mM when added to microbial cells (10(8)/mL) + PF (10 μM hematoporphyrin equivalent) + 415 nm light (10 J/cm(2)) can eradicate (>6 log killing) five different Gram-negative species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii), whereas no killing was obtained without KI. The mechanism of action appears to be the generation of microbicidal molecular iodine (I2/I3(-)) as shown by comparable bacterial killing when cells were added to the mixture after completion of illumination and light-dependent generation of iodine as detected by the formation of the starch complex. Gram-positive methicillin-resistant Staphylococcus aureus is much more sensitive to aPDI (200-500 nM PF), and in this case potentiation by KI may be mediated mainly by short-lived iodine reactive species. The fungal yeast Candida albicans displayed intermediate sensitivity to PF-aPDI, and killing was also potentiated by KI. The reaction mechanism occurs via singlet oxygen ((1)O2). KI quenched (1)O2 luminescence (1270 nm) at a rate constant of 9.2 × 10(5) M(-1) s(-1). Oxygen consumption was increased when PF was illuminated in the presence of KI. Hydrogen peroxide but not superoxide was generated from illuminated PF in the presence of KI. Sodium azide completely inhibited the killing of E. coli with PF/blue light + KI.

  5. Repeated applications of photodynamic therapy on Candida glabrata biofilms formed in acrylic resin polymerized.

    Science.gov (United States)

    de Figueiredo Freitas, Lírian Silva; Rossoni, Rodnei Dennis; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2017-04-01

    Previous studies have been suggested that photodynamic therapy (PDT) can be used as an adjuvant treatment for denture stomatitis. In this study, we evaluated the effects of multiple sessions of PDT on Candida glabrata biofilms in specimens of polymerized acrylic resin formed after 5 days. Subsequently, four applications of PDT were performed on biofilms in 24-h intervals (days 6-9). Also, we evaluated two types of PDT, including application of laser and methylene blue or light-emitting diode (LED) and erythrosine. The control groups were treated with physiological solution. The effects of PDT on biofilm were evaluated after the first and fourth application of PDT. The biofilm analysis was performed by counting the colony-forming units. The results showed that between the days 6 and 9, the biofilms not treated by PDT had an increase of 5.53 to 6.05 log (p = 0.0271). Regarding the treatments, after one application of PDT, the biofilms decreased from 5.53 to 0.89 log. When it was done four applications, the microbial reduction ranged from 6.05 log to 0.11 log. We observed that one application of PDT with laser or LED caused a reduction of 3.36 and 4.64 compared to the control groups, respectively (p = 0.1708). When it was done four applications of PDT, the reductions achieved were 1.57 for laser and 5.94 for LED (p = 0.0001). It was concluded that repeated applications of PDT on C. glabrata biofilms showed higher antimicrobial activity compared to single application. PDT mediated by LED and erythrosine was more efficient than the PDT mediated by laser and methylene blue.

  6. 5-Aminolevulinic acid induced photodynamic inactivation on Staphylococcus aureus and Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Chien-Ming Hsieh

    2014-09-01

    Full Text Available The aim of the present study was to develop a simple and fast screening technique to directly evaluate the bactericidal effects of 5-aminolevulinic acid (ALA-mediated photodynamic inactivation (PDI and to determine the optimal antibacterial conditions of ALA concentrations and the total dosage of light in vitro. The effects of PDI on Staphylococcus aureus and Pseudomonas aeruginosa in the presence of various concentrations of ALA (1.0 mM, 2.5 mM, 5.0 mM, 10.0 mM were examined. All bacterial strains were exponentially grown in the culture medium at room temperature in the dark for 60 minutes and subsequently irradiated with 630 ± 5 nm using a light-emitting diode (LED red light device for accumulating the light doses up to 216 J/cm2. Both bacterial species were susceptible to the ALA-induced PDI. Photosensitization using 1.0 mM ALA with 162 J/cm2 light dose was able to completely reduce the viable counts of S. aureus. A significant decrease in the bacterial viabilities was observed for P. aeruginosa, where 5.0 mM ALA was photosensitized by accumulating the light dose of 162 J/cm2. We demonstrated that the use of microplate-based assays—by measuring the apparent optical density of bacterial colonies at 595 nm—was able to provide a simple and reliable approach for quickly choosing the parameters of ALA-mediated PDI in the cell suspensions.

  7. Comparison of continuous versus pulsed photodynamic antimicrobial therapy for inhibition of fungal keratitis isolates in vitro (Conference Presentation)

    Science.gov (United States)

    Nolan, Nicholas; Durkee, Heather A.; Aguilar, Mariela C.; Arboleda, Alejandro; Relhan, Nidhi; Martinez, Anna; Rowaan, Cornelis; Gonzalez, Alex; Alawa, Karam A.; Amescua, Guillermo; Flynn, Harry W.; Miller, Darlene; Parel, Jean-Marie A.

    2017-02-01

    Fungal keratitis can lead to pain and impaired vision. Current treatment options include antifungal agents and therapeutic penetrating keratoplasty. An emerging option for the management of keratitis is photodynamic antimicrobial therapy (PDAT) which uses a photosensitizer rose bengal activated with green light. Utilizing a pulsed irradiation, rather than the standard continuous irradiation may have a similar antimicrobial effect with less total energy. This study is to compare pulsed and continuous rose bengal mediated PDAT for inhibition of six fungal isolates on agar plates: Fusarium solani, Fusarium keratoplasticum, Aspergillus fumigatus, Candida albicans, Paecilomyces variotti, and Pseudoallescheria boydii. Isolates were mixed with 0.1% rose bengal and exposed to three irradiation conditions: (1) 30-minute continuous (10.8J/cm2), (2) 15-minute continuous (5.4J/cm2), (3) 30-minute pulsed (5.4J/cm2). Plates were photographed at 72 hours and analyzed with custom software. At 72 hours, 30-minute continuous rose bengal mediated PDAT inhibited all six fungal species. Fungal inhibition was analogous between 30-minute continuous and 30-minute pulsed test groups, with the exception of A. fumigatus. The 15-minute continuous irradiation was less effective when compared to both 30-minute continuous and 30-minute pulsed groups. These in vitro results demonstrate the potential strength of pulsed rose bengal mediated PDAT as an adjunct treatment modality for fungal keratitis.

  8. Therapeutic effect of photodynamic therapy combined with targeted delivery of silencing vascular endothelial growth factor (Conference Presentation)

    Science.gov (United States)

    Hsu, Yih-Chih

    2016-03-01

    Photodynamic therapy is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates tumours oxygen-independent hypoxic conditions. Vascular endothelial growth factor (VEGF) is one of the primary factors that affect tumor angiogenesis. Another emerging treatment to cure cancer is the use of interference RNA to silence a specific mRNA sequence. Such treatment requires a delivery system such as liposomes. The nanoparticle size measured was about 30 nm. Cellular uptake study was performed to verify that the nanoparticles have a sigma receptor mediated pathway. Non-targeted LCP NPs did not show significant difference with or without haloperidol but has a lower intensity as than targeted LCP NPs. These results confirm that LCP NPs have a receptor mediated pathway. Cell viability was found to decrease at 25 nM of transfected VEGF siRNA. Combined therapy of PDT and VEGF siRNA showed significant response as compared with PDT and gene therapy alone. In vivo toxicity assay with mice treated with targeted LCP NPs containing control siRNA or VEGF siRNA and non-targeted LCP NPs containing VEGF siRNA did not show any significant difference with the PBS injected group which suggests that there is no toxicity with the dose. It suggests that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.

  9. Inactivation of pathogenic bacteria in food matrices: high pressure processing, photodynamic inactivation and pressure-assisted photodynamic inactivation

    Science.gov (United States)

    Cunha, A.; Couceiro, J.; Bonifácio, D.; Martins, C.; Almeida, A.; Neves, M. G. P. M. S.; Faustino, M. A. F.; Saraiva, J. A.

    2017-09-01

    Traditional food processing methods frequently depend on the application of high temperature. However, heat may cause undesirable changes in food properties and often has a negative impact on nutritional value and organoleptic characteristics. Therefore, reducing the microbial load without compromising the desirable properties of food products is still a technological challenge. High-pressure processing (HPP) can be classified as a cold pasteurization technique, since it is a non-thermal food preservation method that uses hydrostatic pressure to inactivate spoilage microorganisms. At the same time, it increases shelf life and retains the original features of food. Photodynamic inactivation (PDI) is also regarded as promising approach for the decontamination of food matrices. In this case, the inactivation of bacterial cells is achieved by the cytotoxic effects of reactive oxygens species (ROS) produced from the combined interaction of a photosensitizer molecule, light and oxygen. This short review examines some recent developments on the application of HPP and PDI with food-grade photosensitizers for the inactivation of listeriae, taken as a food pathogen model. The results of a proof-of-concept trial of the use of high-pressure as a coadjutant to increase the efficiency of photodynamic inactivation of bacterial endospores is also addressed.

  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. Device for fluorescent control and photodynamic therapy of age-related macula degeneration

    Science.gov (United States)

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

    2004-07-01

    Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

  13. The potential role of functional inhibition of T regulatory cells by anti-TGFβ antibody in photodynamic therapy of renal cancer

    Science.gov (United States)

    Mroz, Pawel; Hamblin, Michael R.

    2011-03-01

    Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of inducing tumor-directed immune response. We hypothesized that PDT could be combined with anti-transforming growth factor (TGF) beta antibody that does not significantly affect the population of cytotoxic T lymphocytes (CTL) but at the same time, has the potential to decrease the immunosuppressive effects of regulatory T-cells (Treg) mediated by TGF beta. This hypothesis was tested with aTGF-beta antibody combined with BPD-mediated PDT in a BALB/c renal cell carcinoma model. Evidence of positive benefits of the combination therapy over individual treatments alone was obtained.

  14. Development of Singlet Oxygen Luminescence Kinetics during the Photodynamic Inactivation of Green Algae.

    Science.gov (United States)

    Bornhütter, Tobias; Pohl, Judith; Fischer, Christian; Saltsman, Irena; Mahammed, Atif; Gross, Zeev; Röder, Beate

    2016-04-13

    Recent studies show the feasibility of photodynamic inactivation of green algae as a vital step towards an effective photodynamic suppression of biofilms by using functionalized surfaces. The investigation of the intrinsic mechanisms of photodynamic inactivation in green algae represents the next step in order to determine optimization parameters. The observation of singlet oxygen luminescence kinetics proved to be a very effective approach towards understanding mechanisms on a cellular level. In this study, the first two-dimensional measurement of singlet oxygen kinetics in phototrophic microorganisms on surfaces during photodynamic inactivation is presented. We established a system of reproducible algae samples on surfaces, incubated with two different cationic, antimicrobial potent photosensitizers. Fluorescence microscopy images indicate that one photosensitizer localizes inside the green algae while the other accumulates along the outer algae cell wall. A newly developed setup allows for the measurement of singlet oxygen luminescence on the green algae sample surfaces over several days. The kinetics of the singlet oxygen luminescence of both photosensitizers show different developments and a distinct change over time, corresponding with the differences in their localization as well as their photosensitization potential. While the complexity of the signal reveals a challenge for the future, this study incontrovertibly marks a crucial, inevitable step in the investigation of photodynamic inactivation of biofilms: it shows the feasibility of using the singlet oxygen luminescence kinetics to investigate photodynamic effects on surfaces and thus opens a field for numerous investigations.

  15. Chlorin e6 conjugated copper sulfide nanoparticles for photodynamic combined photothermal therapy.

    Science.gov (United States)

    Bharathiraja, Subramaniyan; Manivasagan, Panchanathan; Moorthy, Madhappan Santha; Bui, Nhat Quang; Lee, Kang Dae; Oh, Junghwan

    2017-09-01

    The photo-based therapeutic approaches have attracted tremendous attention in recent years especially in treatment and management of tumors. Photodynamic and photothermal are two major therapeutic modalities which are being applied in clinical therapy. The development of nanomaterials for photodynamic combined with photothermal therapy has gained significant attention for its treatment efficacy. In the present study, we designed chlorin e6 (Ce6) conjugated copper sulfide (CuS) nanoparticles (CuS-Ce6 NPs) through amine functionalization and the synthesized nanoparticles act as a dual-model agent for photodynamic therapy and photothermal therapy. CuS-Ce6 NPs showed enhanced photodynamic effect through generation of singlet oxygen upon 670nm laser illumination. The same nanoparticles exerted thermal response under an 808nm laser at 2W/cm(2). The fabricated nanoparticles did not show any cytotoxic effect toward breast cancer cells in the absence of light. In vitro cell viability assay showed a potent cytotoxicity in photothermal and photodynamic treatment. Rather than singular treatment, the photodynamic combined photothermal treatment showed an enhanced cytotoxic effect on treated cells. In addition, the CuS-Ce6 NPs exert a photoacoustic signal for non-invasive imaging of treated cells in tissue-mimicking phantom. In conclusion the CuS-Ce6 NPs act as multimodal agent for photo based imaging and therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Investigation of photodynamic therapy optimization for port wine stain using modulation of photosensitizer administration methods.

    Science.gov (United States)

    Wang, Ying; Zuo, Zhaohui; Liao, Xiaohua; Gu, Ying; Qiu, Haixia; Zeng, Jing

    2013-12-01

    To raise photosensitizer concentration level during the photodynamic therapy process, two new methods of photosensitizer administration were investigated. The first method involves the slow intravenous injection of photosensitizer throughout the first 15 min of irradiation, and the second method involves 30 min fomentation before photosensitizer injection and irradiation. The fluorescence spectra of port wine stain skin were monitored and the therapeutic effect correlated index was calculated with a previously published spectral algorithm. Thirty cases were divided into group A (slow injection of photosensitizer during the first 15 min), group B (fomentation), and group C (control group, traditional injection method), with 10 cases in each group. To analyze the effect of these two new methods, the change of therapeutic effect correlated index values of two photodynamic therapy sessions for each patient were calculated, and the photodynamic therapy outcome was compared. The results showed that the change of therapeutic effect correlated index in group A was slightly more remarkable than that in the control group. The change of therapeutic effect correlated index in group B was similar to that in the control group. Slow injection of photosensitizer during photodynamic therapy has a potential to increase photosensitizer concentration level during photodynamic therapy. However, fomentation before photodynamic therapy has no such potential. There is a need for new methods to be attempted.

  17. Simple, reliable and fast spectrofluorometric method for determination of plasma Verteporfin (Visudyne) levels during photodynamic therapy for choroidal neovascularization.

    Science.gov (United States)

    Aquaron, R; Forzano, O; Murati, J L; Fayet, G; Aquaron, C; Ridings, B

    2002-12-01

    Photodynamic therapy with Verteporfin, a potent photosensitizer dye, is a very effective treatment for age related macular degeneration due to choroidal neovascularization. Photodynamic therapy offers the potential for selective tissue injury in part attributable to preferential localization of Verteporfin, administrated by intravenous infusion, to the choroidal neovascularization complex and irradiation of the complex with non-laser thermal light at 690 nm resulting in at least temporary thrombosis and vessel closure. Verteporfin is a benzoporphyrin derivative monoacid ring A formulated as a unilamellar liposome. In the blood Verteporfin is associated with lipoprotein fractions and is rapidly cleared via a receptor-mediated uptake mechanism due the high expression of LDL receptors in neovascular tissues. Verteporfin was undetectable in plasma 24 hr after infusion of the recommended dose: 6 mg/m2 of body surface area. The main side effect is photosensitivity of skin which is usually short-lived (24-48 hr) with a low incidence (2.3%). As skin photosensitivity depends on circulating rather than tissue drug levels, we investigate the possibility of developing a simple, fast and reliable spectrofluorometric method to measure plasma Verteporfin levels. Fluorescence emission spectrum (550-750 nm) of 1:10 saline diluted plasma with lambda exc=430 nm showed a characteristic emission peak at 692 nm, the height being proportional to the Verteporfin levels. The sensitivity is around 100 ng/ml and the pharmacokinetics of Verteporfin has been studied from 0 to 5 hr after infusion in six patients older than 65 years with age-related macular degeneration.

  18. Photodynamic inactivation of Candida albicans by a tetracationic tentacle porphyrin and its analogue without intrinsic charges in presence of fluconazole.

    Science.gov (United States)

    Quiroga, Ezequiel D; Mora, S Jimena; Alvarez, M Gabriela; Durantini, Edgardo N

    2016-03-01

    The photodynamic inactivation mediated by 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and 5,10,15,20-tetrakis[4-(3-N,N,N-trimethylaminepropoxy)phenyl]porphyrin (TAPP(4+)) were compared in Candida albicans cells. A strong binding affinity was found between these porphyrins and the yeast cells. Photosensitized inactivation of C. albicans increased with both photosensitizer concentration and irradiation time. After 30 min irradiation, a high photoinactivation (∼5 log) was found for C. albicans treated with 5 μM porphyrin. Also, the photoinactivation of yeast cells was still elevated after two washing steps. However, the photocytotoxicity decreases with an increase in the cell density from 10(6) to 10(8) cells/mL. The high photodynamic activity of these porphyrins was also established by growth delay experiments. This C. albicans strain was susceptible to fluconazole with a MIC of 1.0 μg/mL. The effect of photosensitization and the action of fluconazole were combined to eradicate C. albicans. After a PDI treatment with 1 μM porphyrin and 30 min irradiation, the value of MIC decreased to 0.25 μg/mL. In addition, a complete arrest in cell growth was found by combining both effects. TAPP was similarly effective to photoinactivate C. albicans than TAPP(4+). This porphyrin without intrinsic positive charges contains basic amino groups, which can be protonated at physiological pH. Moreover, an enhancement in the antifungal action was found using both therapies because lower doses of the agents were required to achieve cell death.

  19. Investigation of photodynamic effect caused by MPPa-PDT on breast cancer Investigation of photodynamic effect caused by MPPa-PDT

    Science.gov (United States)

    Tian, Y. Y.; Hu, X. Y.; Leung, W. N.; Yuan, H. Q.; Zhang, L. Y.; Cui, F. A.; Tian, X.

    2012-10-01

    Breast cancer is the common malignant tumor, the incidence increases with age. Photodynamic therapy (PDT) is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. Pyropheophorbide-a methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. We are exploring the photodynamic effect caused by MPPa-PDT on breast cancer. The in vitro and in vivo experiments indicate that MPPa is a comparatively ideal photosensitizer which can induce apoptosis in breast cancer.

  20. Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA

    Directory of Open Access Journals (Sweden)

    Yutaka Yonemura

    2017-03-01

    Full Text Available In the past, peritoneal metastasis (PM was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS, therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA could improve detection of small PM.

  1. 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.

  2. 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.

  3. Photodynamic therapy in the prophylactic management of bladder cancer

    Science.gov (United States)

    Nseyo, Unyime O.; Lundahl, Scott L.; Merrill, Daniel C.

    1991-06-01

    Nine patients were treated with red light whole bladder photodynamic therapy (WBPDT): five had mucosal involvement (Ta) and four submucosal invasion (T1). Patients received slow intravenous injection with 2mg/kg body weight of photofrin 48-72 hours before undergoing global light treatment via a 22-French cystoscope with a 400-micron quartz fiber bulb (isotropic) tip fiber. Three months after PDT, eight of the patients had normal cystoscopy, and negative biopsy and urine cytology. Two patients who had recurrences at six and twelve months were retreated with a higher dose (20 J/cm2). They had no increased morbidity and no evidence of recurrent disease six months later. WBPDT should be considered as an important alternative treatment for patients who have recurrent or refractory superficial bladder cancer.

  4. 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.

  5. TransOral Robotic Photodynamic Therapy for the Oropharynx

    Science.gov (United States)

    Quon, Harry; Finlay, Jarod; Cengel, Keith; Zhu, Timothy; O’Malley, Bert; Weinstein, Gregory

    2015-01-01

    Photodynamic therapy (PDT) has been used for head and neck carcinomas with little experience in the oropharynx due to technical challenges in achieving adequate exposure. We present the case of a patient with a second right tonsil carcinoma following previous treatment with transoral robotic surgery (TORS) and postoperative chemoradiation for a left tonsil carcinoma. Repeat TORS for the right tonsil carcinoma reviewed multiple positive surgical margins. The power output from the robotic camera was modified to facilitate safe intraoperative three dimensional visualization of the tumor bed. The robotic arms facilitated clear exposure of the tonsil and tongue base with stable administration of the fluence. Real-time measurements confirmed stable photobleaching with augmentation of the prescribed light fluence secondary to light scatter in the oropharynx. We report a potential new role using TORS for exposure and accurate PDT in the oropharynx. PMID:21333937

  6. Photodynamic properties of vital dyes for vitreoretinal surgery.

    Science.gov (United States)

    Brockmann, Tobias; Steger, Claudia; Dawczynski, Jens

    2012-01-01

    The purpose of this study was to evaluate photodynamic properties of indocyanine green (ICG), brilliant blue G (BBG) and trypan blue (TB) as currently used vital dyes for chromovitrectomy. Under consideration of intraoperative illumination intensities and dye concentrations, a simulative in vitro investigation was set up. Therefore, standardized dilutions of original ICG, BBG and TB vials were irradiated at a wavelength of 366 nm with an intensity of 14 µW/cm2 between 0 and 48 h. After this, all samples were measured spectroscopically in a 220- to 750-nm bandwidth. Analyzing the vital dyes over the time course, an exponential photolysis was observed for ICG, whereas BBG and TB presented photostable properties. Regarding ICG, 5% of the concentration was degraded to toxic metabolites every 20 min. For this reason, our study provides evidence that intraocular dye concentrations and modern endoillumination systems alone cannot fully prevent ICG photodegradation.

  7. Treatment of experimental murine arthritis with transdermal photodynamic therapy

    Science.gov (United States)

    Ratkay, Leslie G.; Chowdhary, R. K.; Neyndorff, Herma C.; Levy, Julia G.; Waterfield, J. D.

    1995-03-01

    Photodynamic therapy (PDT) using benzoporphyrin derivative, monoacid ring A (BPD), and transdermal light was able to significantly treat symptoms of adjuvant-enhanced arthritis in MRL-lpr mice. Clinical and histological evaluation showed that PDT was able to modify the progression of adjuvant-enhanced arthritis up to 10 days after induction. When PDT was used on arthritic joints displaying swelling, it prevented further deterioration of clinical symptoms (76%, 16/21). However, it did not significantly effect the histopathologic parameters. As we have previously reported that mitogen activated MRL-lpr splenocytes were shown to be more susceptible to in vitro PDT we postulate that our findings reflect a selective destruction of adjuvant activated lymphocytes in the circulation and/or joints. The application of PDT to eliminate activated cells responsible for the inflammatory reaction at the arthritic site may have significant clinical implications for the treatment of rheumatoid arthritis.

  8. Light protection of the skin after photodynamic therapy reduces inflammation

    DEFF Research Database (Denmark)

    Petersen, B; Wiegell, S R; Wulf, H C

    2014-01-01

    BACKGROUND: Photodynamic therapy (PDT) is followed by significant inflammation. Protoporphyrin (Pp)IX is still formed in the skin after PDT and patients are sensitive to daylight 24-48 h after treatment. Exposure to daylight after PDT may therefore increase inflammation. OBJECTIVES: To investigate...... whether protection with inorganic sunscreen, foundation or light-blocking plaster after PDT can reduce inflammation caused by daylight-activated PpIX. METHODS: On the right arm of 15 subjects with sun-damaged skin, four identical squares (3 × 3 cm) were given conventional PDT treatment. Immediately after...... red-light illumination the squares were either left unprotected or protected by inorganic sunscreen [sun protection factor (SPF) 50], foundation (SPF50) or light-blocking plaster. The skin was then illuminated with artificial daylight for 2 h and afterwards covered for 24 h. Fluorescence and erythema...

  9. Fat tissue staining and photodynamic/photothermal effects

    Science.gov (United States)

    Tuchin, Valery V.; Altshuler, Gregory B.; Yanina, Irina Yu.; Kochubey, Vyacheslav I.; Simonenko, Georgy V.

    2010-02-01

    Cellulite is considered as a disease of the subcutaneous fat layer that appears mostly in women and consists of changes in fat cell accumulation together with disturbed lymphatic drainage, affecting the external appearance of the skin. The photodynamic and selective photothermal treatments may provide reduction the volume of regional or sitespecific accumulations of subcutaneous adipose tissue on the cellular level. We hypothesize that light irradiation of stained fat tissue at selected temperature leads to fat cell lypolytic activity (the enhancement of lipolysis of cell triglycerides due to expression of lipase activity and cell release of free fat acids (FFAs) due to temporal cell membrane porosity), and cell killing due to apoptosis caused by the induced fat cell stress and/or limited cell necrosis.

  10. Systemic estimation of the effect of photodynamic therapy of cancer

    Science.gov (United States)

    Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.

    1997-12-01

    The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

  11. On the Origin of Photodynamic activity of Perylene Quinone Framework

    Science.gov (United States)

    Parida, Dibyajyoti; Pancharatna, Pattath D.; Balakrishnarajan, Musiri M.

    2016-10-01

    The basic skeleton of perylenequinone is surprisingly ubiquitous in several naturally occurring pigments, such as Hypocrellins, Cercosporin, etc. to name a few. Several of these molecules and their derivatives are also experimentally characterized as potent candidates for photodynamic therapy and are predicted to be aiding the formation singlet Oxygen. Theoretical calculations that unravel the mystery behind the perylenequinone motif in these bio-molecules. Perylenequinone framework has a unique frontier MOs that aid in facile intersystem crossing of the π-π* excitation. The resulting triplet state remarkably resists phosphorescence that presumably leads to high quantum yield of singlet oxygen production. The excitation assisted change in the nature of conjugation and the attendant out-of-plane distortion of the perylene framework is found to be the general characteristic of all these systems and the substituents at the bay region favourably assist the excited state behavior as shown by time dependent/ independent DFT calculations.

  12. Current evidence and applications of photodynamic therapy in dermatology

    Science.gov (United States)

    Wan, Marilyn T; Lin, Jennifer Y

    2014-01-01

    In photodynamic therapy (PDT) a photosensitizer – a molecule that is activated by light – is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancerous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT. PMID:24899818

  13. Photodynamic therapy: treatment of choice for actinic cheilitis?

    Science.gov (United States)

    Rossi, R; Assad, G Bani; Buggiani, G; Lotti, T

    2008-01-01

    The major therapeutic approaches (5-fluorouracil, imiquimod, vermilionectomy, and CO(2) Laser ablation) for actinic cheilitis are aimed at avoiding and preventing a malignant transformation into invasive squamous cell carcinoma via destruction/removal of the damaged epithelium. Recently, photodynamic therapy (PDT) has been introduced as a therapeutic modality for epithelial skin tumors, with good efficacy/safety profile and good cosmetic results. Regarding actinic cheilitis, PDT could be considered a new therapeutic option? The target of our study was to evaluate the efficacy and tolerability of PDT in actinic cheilitis, using a methyl-ester of aminolevulinic acid (MAL) as topical photosensitizing agent and controlled the effects of the therapy for a 30-month follow-up period. MAL-PDT seems to be the ideal treatment for actinic cheilitis and other actinic keratosis, especially on exposed parts such as the face, joining tolerability and clinical efficacy with an excellent cosmetic outcome.

  14. Photodynamic therapy for the treatment of actinic cheilitis.

    Science.gov (United States)

    Kodama, Makiko; Watanabe, Daisuke; Akita, Yoichi; Tamada, Yasuhiko; Matsumoto, Yoshinari

    2007-10-01

    Although actinic cheilitis is a common disease, it should be treated carefully because it can undergo malignant transformation. We report a case of actinic cheilitis treated with photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA), with satisfactory outcome in both clinical and pathological aspects. Actinic cheilitis is a pathologic condition affecting mainly the lower lip caused by long-term exposure of the lips to the UV radiation in sunlight. Analogous to actinic keratosis of the skin, actinic cheilitis is considered as a precancerous lesion and it may develop into squamous cell carcinoma. We report a case of actinic cheilitis treated with PDT using ALA, with satisfactory outcome in both clinical and pathological aspects.

  15. Endoscopic photodynamic therapy of tumors using gold vapor laser

    Science.gov (United States)

    Kuvshinov, Yury P.; Poddubny, Boris K.; Mironov, Andrei F.; Ponomarev, Igor V.; Shental, V. V.; Vaganov, Yu. E.; Kondratjeva, T. T.; Trofimova, E. V.

    1996-01-01

    Compact sealed-off gold vapor laser (GVL) with 2 W average power and 628 nm wavelength was used for endoscopic photodynamic therapy in 20 patients with different tumors in respiratory system and upper gastrointestinal tract. Russian-made hematoporphyrin derivative (Hpd) `Photohem' was used as a photosensitizer. It was given intravenously at a dose of 2 - 2.5 mg/kg body weight 48 hours prior to tumor illumination with 628 nm light from GVL. Intermittent irradiation with GVL was done through flexible endoscope always under local anaesthesia at a power of 200 - 400 mW/sm2 and a dose of 150 - 400 J/sm2. 80% patients showed complete or partial response depending on stage of tumor. In cases of early gastric cancer all patients had complete remission with repeated negative biopsies. No major complication occurred.

  16. 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.

  17. Photodynamic Therapy for Non-Melanoma Skin Cancers

    Science.gov (United States)

    Cohen, Diana K.; Lee, Peter K.

    2016-01-01

    Non-melanoma skin cancer (NMSC) is traditionally treated with surgical excision. Non-surgical 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. PMID:27782043

  18. Photodynamic therapy controls of Staphylococcus aureus intradermal infection in mice.

    Science.gov (United States)

    Almeida, Palloma Porto; Pereira, Ítalo Sousa; Rodrigues, Karine Bitencourt; Leal, Lorena Santos; Marques, Andressa Souza; Rosa, Luciano Pereira; da Silva, Francine Cristina; da Silva, Robson Amaro Augusto

    2017-08-01

    Infections caused by Staphylococcus aureus lead to skin infections, as well as soft tissues and bone infections. Given the communal resistance to antibiotics developed by strains of this bacterium, photodynamic therapy emerges as a promising alternative treatment to control and cure infections. Females of the Balb/C mice were infected with 10(8) CFU of methicillin-resistant S. aureus (MRSA) and divided into four distinct groups: P-L- (negative control group), P+L- (group exposed only to curcumin), P-L+ (group exposed only to LED incidence of 450 nm, 75 mW/cm(2), and 54 J/cm(2) for 10 min), and P+L+ (group exposed to curcumin followed by 10 min of LED irradiation) (n = 24). The mice were euthanized 48 and 72 h after infection, and biologic materials were collected for analysis of the bacterial load, peripheral blood leukocyte counts, and draining lymph nodes cell counts. The normalization of data was checked and the ANOVA test was applied. The bacterial load in the draining lymph node of P+L+ group was lower when compared to the control groups 72 h post infection (p < 0.0001), indicating that the LED incidence associated with curcumin controls of the staphylococci intradermal infection. The number of the total lymph node cells shows to be lower than control groups in the two availed times (p < 0.01). The histological analysis and the counting of white blood cells did not show differences among cells in the blood and in the tissue of infection. This is the first report showing that photodynamic therapy may be effective against MRSA infection in a murine model of intradermal infection.

  19. Photodynamic therapy in the treatment of subfoveal choroidal neovascularisation.

    Science.gov (United States)

    Harding, S

    2001-06-01

    Subfoveal choroidal neovascularisation (CNV) is a major cause of visual disability, with age-related macular degeneration (AMD) the commonest cause. Confluent laser to CNV significantly reduces severe visual loss but the profound visual loss after treatment of subfoveal lesions and the high recurrence rate has meant its restriction to extrafoveal lesions. Developed initially as a treatment for cancers, photodynamic therapy (PDT) has been shown to successfully close CNV in the eye. Large international randomised placebo-controlled studies of the safety and efficacy of PDT with verteporfin are under way. The Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) study has demonstrated a reduction of visual loss in treated patients with any classic CNV. Subgroup analysis showed a greater benefit in predominantly classic lesions (p AMD (VIP) trial, but no benefit in pure occult lesions. Further research is required to establish cost-effectiveness and appropriate referral patterns in the UK and optimise treatment strategies. Further data are awaited from TAP/VIP. At present verteporfin PDT is indicated in eyes with subfoveal predominantly classic CNV secondary to AMD with visual acuity of 6/60 or better and lesions < 5,400 microm in diameter. Juxtafoveal lesions meeting the above criteria and CNV secondary to pathological myopia should also be considered for treatment. The efficacy of treatment of larger lesions, juxtapapillary CNV, occult/no classic with high-risk characteristics (HRC) and CNV from other causes remains unclear. The treatment of minimally classic lesions and those with occult/no classic without HRC is not indicated.

  20. The photodynamic antibacterial effects of silicon phthalocyanine (Pc) 4.

    Science.gov (United States)

    Dimaano, Matthew L; Rozario, Chantal; Nerandzic, Michelle M; Donskey, Curtis J; Lam, Minh; Baron, Elma D

    2015-04-08

    The emergence of antibiotic-resistant strains in facultative anaerobic Gram-positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), is a global health issue. Typically, MRSA strains are found associated with institutions like hospitals but recent data suggest that they are becoming more prevalent in community-acquired infections. It is thought that the incidence and prevalence of bacterial infections will continue to increase as (a) more frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b) increased number of invasive medical procedures; and (c) higher incidence of neutropenia and HIV infections. Therefore, more optimal treatments, such as photodynamic therapy (PDT), are warranted. PDT requires the interaction of light, a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In this study, we investigated the efficacy and characterized the mechanism of cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine (Pc) 4 on (a) methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25923); (b) community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) (ATCC 43300); and (c) hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) (PFGE type 300). Our data include confocal image analysis, which confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell recovery assay, which showed that concentrations as low as 1.0 μM Pc 4 incubated for 3 h at 37 °C followed by light at 2.0 J/cm2 can reduce cell survival by 2-5 logs. These results are encouraging, but before PDT can be utilized as an alternative treatment for eradicating resistant strains, we must first characterize the mechanism of cell death that Pc 4-based PDT employs in eliminating these pathogens.

  1. The Photodynamic Antibacterial Effects of Silicon Phthalocyanine (Pc 4

    Directory of Open Access Journals (Sweden)

    Matthew L. Dimaano

    2015-04-01

    Full Text Available The emergence of antibiotic-resistant strains in facultative anaerobic Gram-positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA, is a global health issue. Typically, MRSA strains are found associated with institutions like hospitals but recent data suggest that they are becoming more prevalent in community-acquired infections. It is thought that the incidence and prevalence of bacterial infections will continue to increase as (a more frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b increased number of invasive medical procedures; and (c higher incidence of neutropenia and HIV infections. Therefore, more optimal treatments, such as photodynamic therapy (PDT, are warranted. PDT requires the interaction of light, a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In this study, we investigated the efficacy and characterized the mechanism of cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine (Pc 4 on (a methicillin-sensitive Staphylococcus aureus (MSSA (ATCC 25923; (b community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA (ATCC 43300; and (c hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA (PFGE type 300. Our data include confocal image analysis, which confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell recovery assay, which showed that concentrations as low as 1.0 μM Pc 4 incubated for 3 h at 37 °C followed by light at 2.0 J/cm2 can reduce cell survival by 2–5 logs. These results are encouraging, but before PDT can be utilized as an alternative treatment for eradicating resistant strains, we must first characterize the mechanism of cell death that Pc 4-based PDT employs in eliminating these pathogens.

  2. Photodynamic Therapy for Head and Neck Dysplasia and Cancer

    Science.gov (United States)

    Rigual, Nestor R.; Thankappan, Krishnakumar; Cooper, Michele; Sullivan, Maureen A.; Dougherty, Thomas; Popat, Saurin R.; Loree, Thom R.; Biel, Merrill A.; Henderson, Barbara

    2009-01-01

    Objective To determine the response of dysplasia, carcinoma in situ (CIS), and T1 carcinoma of the oral cavity and larynx to photodynamic therapy with porfimer sodium. Design Prospective trial. Setting A National Cancer Institute–designated cancer institute. Patients Patients with primary or recurrent moderate to severe oral or laryngeal dysplasia, CIS, or T1N0 carcinoma. Intervention Porfimer sodium, 2 mg/kg of body weight, was injected intravenously 48 hours before treatment. Light at 630 nm for photosensitizer activation was delivered from an argon laser or diode laser using lens or cylindrical diffuser fibers. The light dose was 50 J/cm2 for dysplasia and CIS and 75 J/cm2 for carcinoma. Main Outcome Measures Response was evaluated at 1 week and at 1 month and then at 3-month intervals thereafter. Response options were complete (CR), partial (PR), and no (NR) response. Posttreatment biopsies were performed in all patients with persistent and recurrent visible lesions. Results Thirty patients were enrolled, and 26 were evaluable. Mean follow-up was 15 months (range, 7–52 months). Twenty-four patients had a CR, 1 had a PR, and 1 had NR. Three patients with oral dysplasia with an initial CR experienced recurrence in the treatment field. All the patients with NR, a PR, or recurrence after an initial CR underwent salvage treatment. Temporary morbidities included edema, pain, hoarseness, and skin phototoxicity. Conclusion Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma. PMID:19687399

  3. Apoptosis Induced by Photodynamic Therapy with Benzoporphyrin Derivative Monoacid Ring A and Exploration of its Potential Mechanism in Bladder Cancer Cells

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

    OBJECTIVE To investigate apoptosis induced by photodynamic therapy with benzoporphyrin derivative monoacid ring A (BPD-MA) and explore its potential mechanism in human bladder cancer cells.METHODS Photosensitization of BPD-MA was activated with a red light Laser (632.8nm) delivered at 10 mW/cm2 to give a total dose of 2.4 J/cm2.Cellular apoptosis was measured with flow cytometry analysis and an insitu terminal deoxyuridine nick end-labeling (TUNEL) assay. Changes in mitochondrial membrane potential (△ψm) were monitored by a flow cytometric method with Rhodamine 123 staining and the expression of bcl2 in BIU-87 cells was detected with immunocytochemical staining.RESULTS At 8 h following photodynamic treatment, the degree of apoptosis was significantly increased when analyzed with flow cytometry and TUNEL assay. Treatment of the BIU-87 cells by PDT with BPD-MA resulted in the collapse of the △m and a decrease of bcl-2 expression.CONCLUSION BPD-MA-mediated PDT can effectively induce apoptosis in BIU-87 cells. The mechanism probably is through a mitochondrial-initiated pathway.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.

    Science.gov (United States)

    Lin, Tzu-Yin; Li, Yuanpei; Liu, Qiangqiang; Chen, Jui-Lin; Zhang, Hongyong; Lac, Diana; Zhang, Hua; Ferrara, Katherine W; Wachsmann-Hogiu, Sebastian; Li, Tianhong; Airhart, Susan; deVere White, Ralph; Lam, Kit S; Pan, Chong-Xian

    2016-10-01

    The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 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

  7. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy

    Science.gov (United States)

    He, Chunbai; Duan, Xiaopin; Guo, Nining; Chan, Christina; Poon, Christopher; Weichselbaum, Ralph R.; Lin, Wenbin

    2016-08-01

    Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.

  8. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy.

    Science.gov (United States)

    He, Chunbai; Duan, Xiaopin; Guo, Nining; Chan, Christina; Poon, Christopher; Weichselbaum, Ralph R; Lin, Wenbin

    2016-08-17

    Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.

  9. 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.

  10. 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.

  11. Tumor blood flow differs between mouse strains: consequences for vasoresponse to photodynamic therapy.

    Directory of Open Access Journals (Sweden)

    Rickson C Mesquita

    Full Text Available Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively. However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies.

  12. Cationic ceramides and analogues, LCL30 and LCL85, as adjuvants to photodynamic therapy of tumors.

    Science.gov (United States)

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

    2013-09-05

    Photodynamic therapy (PDT) is known to alter the expression of various genes in treated cells. This prompted us to examine the activity of genes encoding two important enzymes in sphingolipid (SL) metabolism, dihydroceramide desaturase (DES) and sphingosine kinase (SPHK), in mouse SCCVII tumor cells treated by PDT using either the porphyrin-based photosensitizer Photofrin or silicon phthalocyanine Pc4. The results revealed that PDT induced an upregulation in the expression of two major isoforms of both genes (DES1 and DES2 as well as SPHK1 and SPHK2). While the changes were generally moderate (2-3-fold gains), the increase in DES2 expression was more pronounced and it was much greater with Photofrin-PDT than with Pc4-PDT (over 23-fold vs. less than 5-fold). Combining either Photofrin-PDT or Pc4-PDT with the cationic C16-ceramide LCL30 (20mg/kg i.p.) for treatment of subcutaneously growing SCCVII tumors rendered important differences in the therapy outcome. Photofrin-PDT, used at a dose that attained good initial response but no tumor cures, produced 50% cures when combined with a single LCL30 treatment. In contrast, the same LCL30 treatment combined with Pc4-PDT had no significant effect on tumor response. The optimal timing of LCL30 injection was immediately after Photofrin-PDT. The therapeutic benefit was lost when LCL30 was given in two 20mg/kg injections encompassing intervals before and after PDT. LCL85, the cationic B13 ceramide analogue and SL-modulating agent, also increased cure rates of Photofrin-PDT treated tumors, but the therapeutic benefit was less pronounced than with LCL30. These results with LCL30 and LCL85, and our previous findings for LCL29 (another SL analogue), assert the potential of SLs for use as adjuvants to augment the efficacy of PDT-mediated tumor destruction.

  13. The molecular mechanism of photodynamic therapy to fibrosis: Regulation on the pyridinoline cross-link formation in collagen

    Institute of Scientific and Technical Information of China (English)

    ZHANG JuCheng; LIU Wei; YI ZhongZhou; CHEN Rui; LI Ying; MIN Yong

    2009-01-01

    Fibrotic processes in tissues are characterised by an excessive accumulation of collagen containing increased levels of pyridinoline cross-links,which has been taken as an important criterion to diagnose the fibrosis.Hypocrellin B (HB) is a natural photosensitizer with excellent photodynamic activity but very low dark-toxicity.In the current work,main purpose was to clarify if photodynamic action of HB could be applied to regulating the level of pyridinoline cross-link in collagen.To use gelatin as a model collagen,it was observed that the pyridinoline cross-link formation was effectively degraded by HB photodynamic action in the gelatin,suggesting the level of pyridinoline cross-link formation in collagen may be photodynamically regulated to a normal level.Furthermore,mechanism of the photodynamic action of HB was studied.

  14. 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.

  15. Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins

    Directory of Open Access Journals (Sweden)

    Peter Ferenc

    2011-11-01

    Full Text Available In this study we have focused on the response of SKBR-3 cells to both single 17-DMAG treatment as well as its combination with photodynamic therapy with hypericin. Low concentrations of 17-DMAG without any effect on survival of SKBR-3 cells significantly reduced metabolic activity, viability and cell number when combined with photodynamic therapy with hypericin. Moreover, IC10 concentation of 17-DMAG resulted in significant increase of SKBR-3 cells in G1 phase of the cell cycle, followed by an increase of cells in G2 phase when combined with photodynamic therapy. Furthermore, 17-DMAG already decreased HER2, Akt, P-Erk1/2 and survivin protein levels in SKBR-3 cells a short time after its application. In this regard, 17-DMAG protected also SKBR-3 cells against both P-Erk1/2 as well as survivin upregulations induced by photodynamic therapy with hypericin. Interestingly, IC10 concentration of 17-DMAG led to total depletion of Akt, P-Erk1/2 proteins and to decrease of survivin level at 48 h. On the other hand, 17-DMAG did not change HER2 relative expression in SKBR-3 cells, but caused a significant decrease of HER2 mRNA in MCF-7 cells characterized by low HER2 expression. These results show that targeting HSP90 client proteins increases the efficiency of antineoplastic effect of photodynamic therapy in vitro.

  16. 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.

  17. Effects of integrin-targeted photodynamic therapy on pancreatic carcinoma cell.

    Science.gov (United States)

    Zhou, Min; Ni, Qian-Wen; Yang, Shan-Ying; Qu, Chun-Ying; Zhao, Peng-Cheng; Zhang, Jian-Cheng; Xu, Lei-Ming

    2013-10-21

    To investigate the effects of photodynamic therapy with quantum dots-arginine-glycine-aspartic acid (RGD) probe as photosensitizer on the proliferation and apoptosis of pancreatic carcinoma cells. Construction of quantum dots-RGD probe as photosensitizer for integrin-targeted photodynamic therapy was accomplished. After cells were treated with photodynamic therapy (PDT), the proliferation of SW1990 cells were measured by methyl thiazolyl tetrazolium assay. Morphologic changes, cell cycle retardance and apoptosis were observed under fluoroscope and flow cytometry. The expression of myeloid cell leukemia-1 (Mcl-1), protein kinase B (Akt) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA were detected by reverse transcription-polymerase chain reaction. The amount of reactive oxygen species were also evaluated by fluorescence probe. The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibited cell proliferation (P photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibits cell proliferation and increases apoptosis in SW1990 cells.

  18. Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma.

    Science.gov (United States)

    Bae, Byoung-chan; Yang, Su-Geun; Jeong, Seok; Lee, Don Haeng; Na, Kun; Kim, Joon Mee; Costamagna, Guido; Kozarek, Richard A; Isayama, Hiroyuki; Deviere, Jacques; Seo, Dong Wan; Nageshwar Reddy, D

    2014-10-01

    Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Subfoveal choroidal thickness after photodynamic therapy in patients with acute idiopathic central serous chorioretinopathy.

    Science.gov (United States)

    Dang, Yalong; Sun, Xinfeng; Xu, Yongsheng; Mu, Yalin; Zhao, Manli; Zhao, Jing; Zhu, Yu; Zhang, Chun

    2014-01-01

    The purpose of this study was to evaluate changes in subfoveal choroidal thickness after photodynamic therapy in patients with acute idiopathic central serous chorioretinopathy (ICSCR). This was a retrospective observational study conducted in 63 participants. The primary outcome measure was subfoveal choroidal thickness at baseline and 3 days, one week, 4 weeks, and 12 weeks after photodynamic therapy. The secondary outcome measure was indocyanine green angiography at baseline and 4 weeks and 12 weeks after photodynamic therapy. Four weeks after photodynamic therapy, 20 (64.51%) symptomatic eyes showed hypofluorescence corresponding to the area of photodynamic therapy irradiation at the posterior pole. The mean subfoveal choroidal thickness increased significantly from 422±132 μm at baseline to 478±163 μm at day 3 after treatment (P=0.022) and then decreased to 362±113 μm at week 4 (PPhotodynamic therapy using a one third dose of verteporfin may decrease choroidal vascular hyperpermeability and choroidal thickness in patients with acute ICSCR.

  20. Evaluation of Silicon Phthalocyanine 4 Photodynamic Therapy Against Human Cervical Cancer Cells In Vitro and in Mice.

    Science.gov (United States)

    Gadzinski, Jill A; Guo, Jianxia; Philips, Brian J; Basse, Per; Craig, Ethan K; Bailey, Lisa; Comerci, John T; Eiseman, Julie L

    2016-12-01

    Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distrubtion were determined. For in vitro Pc 4 photodynamic therapy cells were irradiated at 667nm at a fluence of 2.5 J/cm(2) at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight h after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm(2). The IC50s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6μM and 0.016μM and >10μM and 0.026μM; as spheroids, IC50s of Pc 4 photodynamic therapy were, 0.26μM and 0.01μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay. Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.

  1. Photodynamic therapy as a treatment for esophageal squamous cell carcinoma in a dog.

    Science.gov (United States)

    Jacobs, T M; Rosen, G M

    2000-01-01

    Intrathoracic esophageal squamous cell carcinoma was diagnosed by endoscopy in an 11-year-old, castrated male Labrador retriever with signs of regurgitation and weight loss. Photodynamic therapy with photofrin was administered three times under endoscopic guidance over a two-month period. A partial response to photodynamic therapy was supported by a reduction in tumor size (noted on serial endoscopic examinations) and by a return to oral alimentation. The dog was euthanized due to recurrent regurgitation and aspiration pneumonia nine months after the onset of therapy. Necropsy revealed marked local invasiveness and regional lymph node metastasis of the esophageal squamous cell carcinoma in addition to pneumonia. The application of photodynamic therapy in the treatment of canine esophageal squamous cell carcinoma is discussed and compared with the human literature.

  2. Photodynamic inactivation of microorganisms which cause pulmonary diseases with infrared light: an in vitro study

    Science.gov (United States)

    Leite, Ilaiáli S.; Geralde, Mariana C.; Salina, Ana C.; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.; Inada, Natalia M.

    2014-03-01

    Lower respiratory infections are among the leading causes of death worldwide. In this study, it was evaluated the interaction of indocyanine green, a photosensitizer activated by infrared light, with alveolar macrophages and the effectiveness of the photodynamic therapy using this compound against Streptococcus pneumoniae . Initial experiments analyzed indocyanine green toxicity to alveolar macrophages in the dark with different drug concentrations and incubation times, and macrophage viability was obtained with the MTT method. The average of the results showed viability values below 90% for the two highest concentrations. Experiments with Streptococcus pneumoniae showed photodynamic inactivation with 10 μM indocyanine green solution. Further experiments with the bacteria in co-culture with AM will be conducted verifying the photodynamic inactivation effectiveness of the tested drug concentrations and incubation periods using infrared light.

  3. Plasmonic Nanoparticle-based Hybrid Photosensitizers with Broadened Excitation Profile for Photodynamic Therapy of Cancer Cells

    Science.gov (United States)

    Wang, Peng; Tang, Hong; Zhang, Peng

    2016-10-01

    Photodynamic therapy combining nanotechnology has shown great potential with improved therapeutic efficacy and fewer side effects. Ideal photosensitizers for cancer treatment should both have good singlet oxygen production capability and be excitable by light illuminations with deep tissue penetration. Here we report a type of hybrid photosensitizers consisting of plasmonic silver nanoparticles and photosensitizing molecules, where strong resonance coupling between the two leads to a broadened excitation profile and exceptionally high singlet oxygen production under both visible light and infrared light excitations. Our results indicate that the hybrid photosensitizers display low cytotoxicity without light illumination yet highly enhanced photodynamic inhibition efficacy against Hela cells under a broad spectrum of light illuminations including the near-infrared light, which has great implication in photodynamic therapy of deep-tissue cancers.

  4. 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.

  5. Photodynamic action of bonellin, an integumentary chlorin of Bonellia viridis, Rolando (Echiura, Bonelliidae).

    Science.gov (United States)

    Agius, L; Jaccarini, V; Ballantine, J A; Ferrito, V; Pelter, A; Psaila, A F; Zammit, V A

    1979-01-01

    1. The photodynamic activity of bonellin, an integumentary chlorin of Bonellia viridis, is investigated. 2. 10(-6) M bonellin solutions haemolyze erythrocytes only in the presence of light. Previous illumination (tungsten lamp 2000-4000 lux for 1 hr) of the bonellin solutions does not affect the results. Under lowered oxygen tensions the bioactivity is depressed. Benzoquinone and singlet oxygen quenchers delay the photodynamic effect. 3. Bonellin (2 x 10(-6) M) destroys echinoid gamete function, depresses oxygen uptake of spermatozoa, and arrests development of echinoid and Bonellia eggs. These effects are produced only in the presence of light. 4. Copper bonellin is not photodynamically active. The role of copper may be to protect against photosensitization.

  6. Inhibitory effect of 5-aminolevulinic acid photodynamic therapy on Candida albicans%5-氨基酮戊酸光动力疗法对白念珠菌抑制效应的实验研究

    Institute of Scientific and Technical Information of China (English)

    梁义; 卢丽明; 陈勇; 尹琦

    2013-01-01

    Objective To evaluate the inhibitory effect of 5-aminolevulinic acid Photodynamic therapy on Candida albicans in vitro. Methods 96-well cell culture plates were used for experimental carriers, and Candida albicans suspension was added to these wells, which were divided into experimental group and four control groups. With He-Ne laser as the excitation source, ALA as photosensitizer, DMSO as penetration enhancer and a solvent, ALA-PDT was performed. Results The growth of Candida albicans was inhibited in experimental group, with MIC of 500 mg/ml (50%). At concentration of 200 mg/ml (20%), ALA began to inhibit the growth of Candida albicans in experimental group, and ALA inhibited the growth of Candida albicans in a concentration-dependent way. The growth of Candida albicans was not inhibited in four control groups, and the CFU of Candida albicans showed no statistically significant difference between the groups. Conclusion ALA-PDT can effectively inhibit the growth of Candida albicans.%目的 评估5-氨基酮戊酸光动力疗法(5-ALA-PDT)在体外对白念珠菌的抑制效应.方法 以96孔细胞培养板为实验载体,加入白念珠菌悬液,分为治疗组和4个对照组,以氦氖激光为激发光源,ALA为光敏剂,使用DMSO作为ALA的溶剂兼穿透增强剂,进行ALA-PDT.结果 治疗组白念珠菌的生长受到抑制,其MIC值为500mg/ml(50%),ALA浓度在200mg/ml(20%)时,开始使治疗组白念珠菌的生长受到抑制,且抑制作用对ALA的浓度呈剂量依赖关系.而对照组中白念珠菌的生长未受到抑制,四组的白念珠菌的CFU数量变化无明显差异.结论 按本实验所使用的方法进行的ALA-PDT能有效地抑制白念珠菌.

  7. Pc 4 photodynamic therapy of U87 (human glioma) orthotopic tumor in nude rat brain

    Science.gov (United States)

    Dean, David; George, John E., III; Ahmad, Yusra; Wolfe, Michael S.; Lilge, Lothar; Morris, Rachel L.; Peterson, Allyn; Lust, W. D.; Totonchi, Ali; Varghai, Davood; Li, Xiaolin; Hoppel, Charles L.; Sun, Jiayang; Oleinick, Nancy L.

    2005-04-01

    Introduction: Photodynamic therapy (PDT) for Barrett"s esophagus, advanced esophageal cancer, and both early and late inoperable lung carcinoma is now FDA-approved using the first generation photosensitizer PhotofrinTM (Axcan Pharma, Birmingham, AL). Photofrin-mediated PDT of glioma is now in Phase III clinical trials. A variety of second generation photosensitizers have been developed to provide improved: (1) specificity for the target tissue, (2) tumoricidal capability, and (3) rapid clearance the vascular compartment, skin, and eyes. The phthalocyanine Pc 4 is a second generation photosensitizer that is in early phase I clinical trials for skin cancer. We have undertaken a preclinical study that seeks to determine if Pc 4-mediated PDT can be of benefit for the intra-operative localization and treatment of glioma. Methods: Using a stereotactic frame, 250,000 U87 cells were injected via Hamilton syringe through a craniotomy, and the dura, 1-2 mm below the cortical surface of nude (athymic) rat brains (N=91). The craniotomy was filled with a piece of surgical PVC and the scalp closed. After two weeks of tumor growth, the animals received 0.5 mg/kg Pc 4 via tail vein injection. One day later the scalp was re-incised, and the PVC removed. The tumor was then illuminated with either 5 or 30 Joule/cm2 of 672-nm light from a diode laser at 50 mW/cm2. The animals were sacrificed one day later and the brain was cold-perfused with formaldehyde. Two thirds of the explanted brains are now being histologically surveyed for necrosis after staining with hematoxylin and eosin and for apoptosis via immunohistochemistry (i.e., TUNEL assay). The other third were analyzed by HPLC-mass spectrometry for the presence of drug in tumor, normal brain, and plasma at sacrifice. Initial histological results show PDT-induced apoptosis and necrosis confined to the growing (live) portion of the tumor. Preliminary analysis shows an average selectivity of Pc 4 uptake in the bulk tumor to be 3

  8. Photosensitizer anchored gold nanorods for targeted combinational photothermal and photodynamic therapy.

    Science.gov (United States)

    Tham, Huijun Phoebe; Chen, Hongzhong; Tan, Yu Hui; Qu, Qiuyu; Sreejith, Sivaramapanicker; Zhao, Lingzhi; Venkatraman, Subbu S; Zhao, Yanli

    2016-07-07

    Silylated zinc phthalocyanine (ZnPc) was anchored onto silica-coated gold nanorods (AuNR) with retained local surface plasmon resonance (LSPR). Independent LSPR and singlet oxygen production of anchored ZnPc enhance the photothermal and photodynamic efficacy of the obtained AuNR-Si-ZnPc under NIR light excitation. AuNR-Si-ZnPc was further grafted with hyaluronic acid (HA). Since HA has selective targeting capability to CD44 antigens, the final hybrid could target cancer cells directly for synergistic photothermal and photodynamic therapy.

  9. 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.

  10. Enhanced cellular uptake of protoporphyrine IX/linolenic acid-conjugated spherical nanohybrids for photodynamic therapy.

    Science.gov (United States)

    Lee, Hye-In; Kim, Young-Jin

    2016-06-01

    Protoporphyrin IX (PpIX) has wide applications in photodynamic diagnosis and photodynamic therapy (PDT) in many human diseases. However, poor water solubility and cancer cell localization limit its direct application for PDT. We improved the water-solubility and cellular internalization of PpIX to enhance PDT efficacy by developing biocompatible PpIX/linolenic acid-conjugated polyhedral oligomeric silsesquioxane (PPLA) nanohybrids. The resulting PPLA nanohybrids exhibited a quasi-spherical shape with a size of gastric cancer cells. These results imply that the PPLA nanohybrid system may be applicable in PDT.

  11. Cationic porphyrin derivatives for application in photodynamic therapy of cancer

    Science.gov (United States)

    Prack McCormick, Bárbara P.; Florencia Pansa, M.; Milla Sanabria, Laura N.; Carvalho, Carla M. B.; Faustino, M. Amparo F.; Neves, Maria Graça P. M. S.; Cavaleiro, José A. S.; Rumie Vittar, Natalia B.; Rivarola, Viviana A.

    2014-04-01

    Current studies in photodynamic therapy (PDT) against cancer are focused on the development of new photosensitizers (PSs), with higher phototoxic action. The aim of this study was to compare the therapeutic efficiency of tri-cationic meso-substituted porphyrin derivatives (Tri-Py+-Me-PF, Tri-Py+-Me-Ph, Tri-Py+-Me-CO2Me and Tri-Py+-Me-CO2H) with the well-known tetra-cationic T4PM. The phototoxic action of these derivatives was assessed in human colon adenocarcinoma cells by cell viability, intracellular localization and nuclear morphology analysis. In the experimental conditions used we determined that after light activation -PF, -Ph and -CO2Me cause a more significant decline of cell viability compared to -CO2H and T4PM. These results suggest that the nature of the peripheral substituent influences the extent of cell photodamage. Moreover, we have demonstrated that PS concentration, physicochemical properties and further light activation determine the PDT response. All porphyrins were clearly localized as a punctuated pattern in the cytoplasm of the cells, and the PDT scheme resulted in apoptotic cell death after 3 h post-PDT. The tri-cationic porphyrin derivatives Tri-Py+-Me-PF, Tri-Py+-Me-Ph and Tri-Py+-Me-CO2Me showed a promising ability, making them good photosensitizer candidates for oncological PDT.

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

    Directory of Open Access Journals (Sweden)

    Takayuki Baba

    2011-04-01

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

  13. Characterizing light propagation in bone for photodynamic therapy of osteosarcoma

    Science.gov (United States)

    Rossi, Vincent M.; Gustafson, Scott B.; Jacques, Steven L.

    2009-02-01

    This work aims at characterizing how light propagates through bone in order to efficiently guide treatment of osteosarcoma with photodynamic therapy (PDT). Optical properties of various bone tissues need to be characterized in order to have a working model of light propagation in bone. Bone tissues of particular interest include cortical bone, red and yellow marrow, cancellous bone, and bone cancers themselves. With adequate knowledge of optical properties of osseous tissues, light dosimetry can determine how best to deliver adequate light to achieve phototoxic effects within bone. An optical fiber source-collector pair is used for diffuse reflectance spectroscopic measurements in order to determine the scattering and absorption properties of bone tissues. Native absorbers of interest at visible and near-IR wavelengths include water and oxygenated and deoxygenated hemoglobin. A cylindrically symmetric Monte Carlo model is then used, incorporating these results, in order to predict and guide the delivery of light within bone in order to achieve the desired phototoxic effect in PDT.

  14. 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.

  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. Combined laser and photodynamic treatment in extensive purulent wounds

    Science.gov (United States)

    Solovieva, A. B.; Tolstih, P. I.; Melik-Nubarov, N. S.; Zhientaev, T. M.; Kuleshov, I. G.; Glagolev, N. N.; Ivanov, A. V.; Karahanov, G. I.; Tolstih, M. P.; Timashev, P. S.

    2010-05-01

    Recently, photodynamic therapy (PDT) has been used for the treatment of festering wounds and trophic ulcers. An important advantage of PDT is its ability to affect bacterial cultures that are resistant to antibiotics. However the use of PDT alone does not usually guarantee a stable antiseptic effect and cannot prevent an external infection of wounds and burns. In this work attention is focused on the healing of the extensive soft tissues wounds with combined laser therapy (LT) and PDT treatment. At the first stage of this process festering tissues (for example spacious purulent wounds with ar