Poly(PEGA)-b-poly(l-lysine)-b-poly(l-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubic

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• 作者：Renjith P. Johnson ; Saji Uthaman ; Johnson V. John ; Hye Ri Lee ; Sang Joon Lee ; Huiju Park ; In-Kyu Park ; Hongsuk Suh ; Il Kim
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：October 7, 2015
• 年：2015
• 卷：7
• 期：39
• 页码：21770-21779
• 全文大小：463K
• ISSN：1944-8252

文摘

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鈥?00 渭g/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.