Poly(PEGA)-b-poly(L-lysine)-b-poly(L-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride

A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine)-block-poly(L-histidine) [p(PEGA)(30)-b-p(Lys)(25)-b-p(His)(n)] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 mu g/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of fox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release fox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery.