Insulin-mediated intracellular targeting enhances the photodynamic activity of chlorin e(6)статья
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Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
Аннотация:Photodynamic therapy has been applied quite extensively over the last few years, whereby the activation of photosensitizers by light causes the production of reactive oxygen species such as singlet oxygen, which is cytotoxic. The goal of this study was the enhancement of the photodynamic activity of photosensitizers through their delivery to specific, sensitive intracellular compartments of target cells. We synthesized a BSA-insulin-chlorin e(6) conjugate that bound specifically to the insulin receptors (EC(50), 1 nM) of the human hepatoma cell line PLC/PRF/5 and could be internalized by receptor-mediated endocytosis. Photodynamic activity, as assessed by various tests, indicated EC(50)s at about 100 times lower concentrations of conjugate compared to free chlorin e(6) itself; and lower doses of irradiation were necessary to activate the conjugate compared to free chlorin e(6). Inhibition of endocytosis of the conjugate abrogated the enhanced photodynamic activity of the conjugate above that of free chlorin e(6). Endocytosis and subsequent localization around and in the cell nucleus of the BSA-insulin-chlorin e(6) conjugate could be visualized using both FITC-labeled conjugate and 2',7'-dichlorofluorescin diacetate, a fluorescent indicator of the production of active oxygen species due to chlorin e(6) activation. It was concluded that photodynamic activity of the conjugate is higher than that of free chlorin e(6) through its receptor-mediated delivery into sensitive intracellular compartments.