Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai 200062 , PR China.
Department of Radiology and Nuclear Medicine, Changzheng Hospital , Naval Medical University , Shanghai 200003 , PR China.
Biomacromolecules. 2019 Mar 11;20(3):1167-1177. doi: 10.1021/acs.biomac.8b01430. Epub 2019 Feb 11.
A biodegradable brush-type copolymer PHF- g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.
本文合成了一种基于可裂解聚缩醛主链和可生物降解侧链的聚己内酯-聚乙二醇接枝的生物可降解刷型共聚物 PHF-g-(PCL-PEG)。这种特殊的结构有利于形成球形或棒状胶束。流式细胞术表明，与球形胶束相比，棒状胶束具有增强的细胞摄取能力。选择棒状胶束来详细研究其药物传递能力。体外实验验证了载 DOX 胶束的 pH 触发药物释放，在 pH 5.0 时 DOX 的释放率为 77%，在 pH 7.4 时为 26%。在药物释放动力学分析中，双指数模型拟合度最佳。共聚物几乎没有毒性，而载 DOX 胶束在高浓度时与 DOX 表现出等效的细胞毒性。载 DOX 胶束的内吞作用是 DOX 的两倍。我们的研究结果表明，pH 敏感刷型共聚物可能是药物传递的一种潜在载体。
