Poly(PEGA)‑<i>b</i>‑poly(l‑lysine)‑<i>b</i>‑poly(l‑histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride

Abstract

A series of poly­(ethylene glycol) methyl ether acrylate-<i>block</i>-poly­(l-lysine)-<i>block</i>-poly­(l-histidine) [p­(PEGA)₃₀-<i>b</i>-p­(Lys)₂₅-<i>b</i>-p­(His)_<i>n</i>] (<i>n</i> = 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 μg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. 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 Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery