Phototoxicity photodynamic therapy

The obtained results have shown that cell cultures of tumor origin are more sensitive to phototoxic damage induced by solid-phase C60 than the cultures of nontumor origin (normal or spontaneously transformed ones) - the effect that could be interesting for the perspective of possible fullerene usage in photodynamic therapy of tumors. 

Photodynamic ACT (PACT), similar to photodynamic therapy (PDT) described in Chapter 17, utilizes photosensitizers and visible or UV light in order to induce a phototoxic response, usually via oxidative damage. For some time the disinfection of blood products, particularly for viral inactivation, has been the major use of PACT, although more and more clinically based protocols are being developed, eg in the treatment of oral infections. The technique has been shown to be effective in vitro against bacteria (including drug resistance strains), yeasts, viruses, and parasites. 

Singlet oxygen is involved in many important chemical processes and photochemical applications, including photodynamic therapy (Special Topic 6.23), photocarcinogeneity (Special Topic 6.7) and phototoxicity (Special Topic 6.22), chemiluminescence (Section 5.6), atmospheric photochemistry (Special Topic 6.21), polymer degradation (Special Topic 6.13), photosynthesis1389 (Special Topic 6.25) or industrial organic synthesis (Special Topic 6.20). 

Explain the following concepts and keywords photooxygenation stratospheric ozone depletion singlet oxygen photochemical smog photosensitivity phototoxicity photoallergy photodynamic therapy photoinhibition chemiluminescence perepoxide. 

One of the major side effects of these first generation photosensitizers is prolonged skin photosensitivity, requiring sun and light protection for 1-2 months. Another interesting approach utilises antibody-targeted photodynamic therapy. The use of zinc phthalocyanine antibody-MCA complex improved tumor selectivity, avoided skin phototoxicity and resulted in partial remission of the chest wall metas-tases [17]. 

Skin Photodynamic therapy causes selective destruction of abnormal cells by activating a photosensitizer in the presence of oxygen. Local phototoxic reactions and pain are the most common limiting adverse reactions. In a randomized comparison in healthy volimteers of the local phototoxic response to photodynamic therapy with 5-aminolevulinic acid 20% or methylaminolevulinate 160 mg/g cream, pain, detection of substance P, change in fluorescence intensity from before to 5 hours after cream application, and adverse reactions not related to local phototoxicity were studied [57 ]. Aminolevulinic acid and methylaminolevulinate caused equivalent frequencies of local adverse reactions, except for a higher frequency and extent of hyperpigmentation after exposure to aminolevulinic acid for 28 days. 

Steinbauer J, Schreml S, Karrer S, Ackermann G, Babilas P, Landthaler M, Szeimies RM. Phototoxic reactions in healthy volunteers following photodynamic therapy with methylaminolevulinate cream or with cream containing 5-aminolevulinic acid a phase II, randomized study. Photo-dermatol Photoimmunol Photomed 2009 25(5) 270-5. 

Severe phototoxic reactions occurred in four patients undergoing methylaminole-vulinate photodynamic therapy for histologically confirmed basal cell carcinomas or actinic keratosis on the nose [29 ]. All complained of severe discomfort, burning, and a stinging sensation during irradiation. They also developed severe phototoxic reactions, with erythema, edema, and crust formation, which spread widely outside the clinically affected areas. After topical mupirodn there was complete healing within 7 days with excellent cosmetic results. 

Toll A, Parera ME, Velez M, Pujol RM. Photodynamic therapy with methyl amino-levulinate induces phototoxic reactions on areas of the nose adjacent to basal cell carcinomas and actinic keratoses. Dermatol Surg 2008 34(8) 1145-7. 

These PpIX-loaded chitosan-based nanoparticles (PpIX-CNPs) showed a sustained release profile of PpIX and were biocompatible to tumor cells without irradiation. With SCC7 murine cell carcinoma cells, we observed fast cellular uptake of the PpIX-CNPs and the released PpIX exhibited high phototoxicity after laser irradiation. In vivo imaging and therapy with SCC7 tumor-bearing mice showed enhanced tumor specificity and increased therapeutic efficacy of PpIX-CNPs compared to free PpDC. These results indicated that these chitosan-based nanoparticle systems have great potential as fine delivery system for photodynamic therapy. 

In addition, two-photon excitation can be another effective way to achieve NIR-triggered PDT/PTT synergistic therapy. For example, Li and coworkers also prepared hypocrellin-loaded AuNCs for two-photon PDT/PTT of cancer. The AuNCs were optimized to have efficient NIR absorption and further coated with lipids containing hydrophobic photosensitizer hypocrellin B (HB). The photodynamic effect of the photosensitizer was quenched in the Au nanostructure, thereby reducing side effects of the photosensitizer in unintended locations. For in vitro experiments, cancer cells were treated with the nanocomplex and irradiated with a 790 nm pulsed NIR laser. The photosensitizer HB was released from the AuNCs in the intracellular region, which induced dramatic phototoxicity due to the synergistic effect of PDT and PTT under two-photon irradiation. 

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