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A Cationic Nano-micellar Complex of the Quaternary Amphiphilic Amine RC16+ with Fenretinide as a New Multitask System for Antitumor Therapy.

This study investigated the antitumor effect of a new nano-micellar complex obtained by combining the antitumor agent fenretinide with a quaternary amphiphilic amine RC16+ also endowed with antitumor activity. The complex (Fen-RC16+) strongly improved the aqueous solubility of fenretinide (from 1,71 μg/ml, pure fenretinide, to 1500 μg/ml Fen-RC16+ complex) and provided a cytotoxic effect on SH-SY5Y neuroblastoma cell lines resulting from the intrinsic activity of both the complex components. Moreover, the mean size of the nano-micellar complex (ranging from 20 nm to 40 nm) was suitable for accumulation to the tumor site by the enhanced permeability and retention effect and the positive charge provided by the quaternary RC16+ induced adsorption of the complex on the tumor cell surface improving the intracellular concentration of fenretinide. All these characteristics made the Fen-RC16+ complex a multitasking system for antitumor therapy. Indeed its in-vivo activity, evaluated on SH-SY5Y xenografts, was strong, and the tumor growth did not resume after the treatment withdrawal.