Specific properties of chlorin e₆ trimethyl ester and its glycolized derivative as photosensitizers in vitro and in vivo

The aim of the study was to compare the biodistribution and the photodynamic efficacy of the chlorin е₆ trimethyl ester (3MeChl) and its galactose-substituted in pyrrole A derivative (3MeChl_gal_NoAc). Materials and methods. In vitro experiments were carried out on cultivated murine Lewis lung carcinoma (LLC) cells using multipara-metric mode. Biodistribution and therapeutic efficacy of 3MeChl 3MeChl_gal_NoAc were studied in BDF1 mice bearing s. c. transplanted LLC. The biodistribution study was performed using local fluorescence spectroscopy. For evaluation of the photoinduced antitu- mor activity the photosensitizer was administered i. v. on day 7 of tumor growth in doses varyingfrom 0.5 to 7.5 mg/kg. The tumors were irradiated by LED source with a wavelength of the emitted light 661+/ - 16 nm, at various drug-light time interval (from 5 to 120 min), and at energy density 90 J/cm². Results. It was shown in cultured murine Lewis lung carcinoma cells that 3MeChl_gal_NoAc has higher photo-induced cytotoxicity than the unsubstituted compound (IC₀₀ value of 25 ± 1.5 nM and 171 ± 4.0 nM, respectively). When administered intravenously to mice with subcutaneous LLC a normalized fluorescence intensity of 3MeChl in tumor reached the maximum value (18.4 ± 0.7 a. u.) within 60 min, and for MeChlgalNoAc it reached the maximum value (34.1 ± 6.9 a. u.) within 15 min. A higher fluorescent contrast between tumor and normal skin or muscle was registered for 3MeChl (up to 7.4 and 4.1, respectively) than for 3MeChl_gal_NoAc (up to 5.0 and 2.5, respectively). Having similar biodistribution profile in normal organs and tissues of tumor-bearing mice, 3MeChl_gal_ NoAc was eliminatedfrom the body faster than 3MeChl. Intravenous administration of 3MeChl_gal_NoAc in dose of 5.0 mg/kg following 15 min light exposure (light dose 90 J/cm²) with a drug-light interval of 5 min caused a high antitumor effect, 100 % of animals were cured. However, a rapid elimination of the galactosyl derivative from the tumor tissue, a low selectivity of photodynamic damage of the tumor, as well as a narrow range of highly effective therapeutic doses considerably limit prospects for this modification of chlorin е₆ for photodynamic treatment of the malignant tumors.

фотосенсибилизатор, гликозилированное производное хлорина е6, фотоиндуцированная противоопухолевая активность, биораспределение, photosensitizer, galactose-substituted chlorine е₆ derivative, photo-induced antitumour activity, biodistribution

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