Optimizing the antitumor selectivity of PVP-Hypericin re A549 cancer cells and HLF normal cells through pulsed blue light

摘要

Photodynamic therapy (PDT) is based on the preferential accumulation of photo-sensitizer in cancer cells with subsequent cytotoxicity mediated by singlet oxygen production after light excitation. As photosensitizers accumulate also in the surrounding non-cancer cells, the risk of damaging them by photosensitization is a limitation of PDT. Thus, minimizing the side-effects of PDT on normal cells is one of the challenging problems in medical practice. This paper studies the PDT side-effects of PVP-Hypericin (PVP: polyvinylpyrrolidone) photosensitizer excited with continuous or pulsed irradiation, on combined cell lines of human lung carcinoma epithelial cells (A549) and normal primary human lung fibroblast cells (HLF). In vitro PDTs are performed using pulsed or continuous irradiation with irradiance intensities I~* = 1.59, 6.34 and 14.27 mW/cm~2. The LED pulse lengths L are 0.127, 1.29, 13, 54.5 and 131 ms. Then fluorescence and phototoxicity of PVP-Hypericin in the A549 cancer cells are compared with those of HLF normal cells. Although, PVP-Hypericin accumulates more in A549 cancer cells, the results show that HLF cells produce dose-dependent photoreactions in the presence of photosensitizer. PVP-Hypericin induces the most optimized anticancer efficacy with moderate side-effects for I~* = 14.27 mW/cm~2 and L = 131 ms.