Rod-Shaped Micelles Based on PHF- g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake.
Rod-Shaped Micelles Based on PHF- g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake.
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DOI：
10.1021/acs.biomac.8b01430
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发表时间：
2019-01
影响因子：
6.2
通讯作者：
Yanqiang Wu;Yi Xiao;Yushu Huang;Yanyun Xu;Donglei You;Wei Lu;Jiahui Yu
中科院分区：
文献类型：
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作者：
Yanqiang Wu;Yi Xiao;Yushu Huang;Yanyun Xu;Donglei You;Wei Lu;Jiahui Yu
以聚缩醛为骨架，聚乙二醇（PEG）为修饰侧链，合成了一种可生物降解的刷型共聚物PHF- g-（PCL-PEG）。这种特殊的结构是定向的，以促进球形或棒状胶束的形成。流式细胞仪显示，棒状胶束显示增强的细胞摄取相比，球形胶束。以棒状胶束为研究对象，详细考察了其药物释放性能。体外实验证实了载阿霉素胶束的pH触发释药作用，在pH 5.0和pH 7.4时，阿霉素（DOX）的释放率分别为77%和26%。在药物释放动力学分析中，双指数模型达到最佳拟合。共聚物似乎是几乎无毒的，而DOX-负载胶束显示等效的细胞毒性相比，在高浓度的DOX。阿霉素胶束的内吞作用是阿霉素的2倍。我们的研究结果表明，pH敏感刷型共聚物可能是一种可能的药物载体。
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.