Photodynamic Therapy: Current Evidence and Applications in Dermatology
ABSTRACT Photodynamic therapy (PDT) involves the activation of a photosensitizing drug, which preferentially localizes to diseased skin, by irradiation with light to cause selective cytotoxic damage. Since its discovery in the early 20th century and the development of topical photosensitizers 2 decades ago, PDT is increasingly being used in dermatology for a wide range of neoplastic, inflammatory, and infectious cutaneous conditions. Topical 5-aminolevulinic acid and methyl aminolevulinic acid, the most commonly used agents in PDT, have received Food and Drug Administration approval for the treatment of actinic keratoses, and many second-generation photosensitizers are under investigation. Compared with conventional therapies, PDT has the advantage of being noninvasive and capable of field treatment. It is also associated with quicker recovery periods and excellent cosmetic results. Because of these benefits, PDT is being evaluated as a potential treatment option for many dermatologic conditions and has been shown to be effective for certain nonmelanoma skin cancers. Although research is still limited, PDT might also have a therapeutic benefit for cutaneous T-cell lymphoma, acne, psoriasis, leishmaniasis, and warts, among others. This article is a review of the clinical applications of PDT in dermatology and summarizes the current evidence in literature describing its efficacy, safety, and cosmetic outcome.
- SourceAvailable from: Jorge Soriano[Show abstract] [Hide abstract]
ABSTRACT: It is generally accepted that compounds of nanomolecular size penetrate into cells by different endocytic processes. The vehiculization strategy of a compound is a factor that could determine its uptake mechanism. Understanding the influence of the vehicle in the precise mechanism of drug penetration into cells makes possible to improve or modify the therapeutic effects. In this study, using human A-549 cells, we have characterized the possible internalization mechanism of the photosensitizer Zn(II)-phthalocyanine (ZnPc), either dissolved in dimethylformamide (ZnPc-DMF) or included in liposomes of dipalmitoyl-phosphatidyl-choline. Specific inhibitors involved in the main endocytic pathways were used. Co-incubation of cells with ZnPc-liposomes and dynasore (dinamin-mediated endocytosis inhibitor) resulted in a significant decrease of photodamage, whereas other inhibitors did not alter the photodynamic effect of ZnPc. On the contrary, cells treated with ZnPc-DMF in the presence of dynasore, genistein (caveolin-mediated endocytosis inhibitor) or cytochalasin D (macropinocytosis and caveolin-mediated endocytosis inhibitor) showed a significant decrease in ZnPc uptake and photodynamic damage. These results suggest that ZnPc-DMF penetrates into cells mainly by caveolin-mediated endocytosis, whereas ZnPc-liposomes are internalized into cells preferentially by clathrin-mediated endocytosis. We conclude that using different drug vehiculization systems, it is possible to modify the internalization mechanism of a therapeutic compound, which could be of great interest in clinical research.Histochemie 08/2012; DOI:10.1007/s00418-012-1012-6
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ABSTRACT: Basal cell carcinoma (BCC) is the most common human tumor. Mutations in the hedgehog (HH) receptor Patched (PTCH) are the main cause of BCC. Due to their high and increasing incidence, BCC are becoming all the more important for the health care system. Adequate animal models are required for the improvement of current treatment strategies. A good model should reflect the situation in humans (i.e., BCC initiation due to Ptch mutations on an immunocompetent background) and should allow for (i) BCC induction at a defined time point, (ii) analysis of defined BCC stages, and (iii) induction of BCC in 100% of animals. In addition, it should be easy to handle. Here, we compare several currently existing conventional and conditional Ptch knockout mouse models for BCC and their potential use in preclinical research. In addition, we provide new data using conditional Ptch(flox/flox) mice and the K5-Cre-ER(T+/-) driver.09/2012; 2012:907543. DOI:10.1155/2012/907543
Article: Ocular phototherapy[Show abstract] [Hide abstract]
ABSTRACT: Phototherapy can be translated to mean 'light or radiant energy-induced treatment.' Lasers have become the exclusive source of light or radiant energy for all applications of phototherapy. Depending on the wavelength, intensity, and duration of exposure, tissues can either absorb the energy (photocoagulation, thermotherapy, and photodynamic therapy (PDT)) or undergo ionization (photodisruption). For phototherapy to be effective, the energy has to be absorbed by tissues or more specifically by naturally occurring pigment (xanthophyll, haemoglobin, and melanin) within them. In tissues or tumours that lack natural pigment, dyes (verteporphin, Visudyne) with narrow absorption spectrum can be injected intravenously that act as focal absorbent of laser energy after they have preferentially localized within the tumour. Ocular phototherapy has broad applications in treatment of ocular tumours. Laser photocoagulation, thermotherapy, and PDT can be delivered with low rates of complications and with ease in the outpatient setting. Review of the current literature suggests excellent results when these treatments are applied for benign tumours, particularly for vascular tumours such as circumscribed choroidal haemangioma. For primary malignant tumours, such as choroidal melanoma, thermotherapy, and PDT do not offer local tumour control rates that are equivalent or higher than those achieved with plaque or proton radiation therapy. However, for secondary malignant tumours (choroidal metastases), thermotherapy and PDT can be applied as a palliative treatment. Greater experience is necessary to fully comprehend risks, comparative benefits, and complication of ocular phototherapy of ocular tumours.Eye advance online publication, 14 December 2012; doi:10.1038/eye.2012.258.Eye (London, England) 12/2012; 27(2). DOI:10.1038/eye.2012.258