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首页> 外文期刊>RSC Advances >Acetalated-dextran as valves of mesoporous silica particles for pH responsive intracellular drug delivery
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Acetalated-dextran as valves of mesoporous silica particles for pH responsive intracellular drug delivery

机译：乙酸葡聚糖作为中孔二氧化硅颗粒的阀门，用于pH响应的细胞内药物递送

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摘要

A pH-sensitive drug release system using acetalated-dextran as valves was designed to manipulate smart intracellular release of anticancer drugs. Dextran was grafted onto the exterior of MSN through a click reaction, and followed by acetalation to generate the final carriers of MSN-Dex-Ac. The hydrophobic Dex-Ac would act as valves on the MSN surface to block the entrapped drugs inside the MSN pores. While under acidic conditions mimicking the micro-environment of endosomal/lysosomal compartments, the valves could be opened by acetal hydrolysis to recover the acetalated-dextran to its hydrophilic state, resulting in fast drug release. In vitro drug release profile clearly showed that DOX release was restricted at pH 7.4 by the valves, while it was accelerated under acidic conditions. Fast endocytosis and intracellular DOX release was observed by confocal laser scanning microscopy (CLSM). Cytotoxicity evaluation showed good biocompatibility with the carriers. In vitro MTT assays revealed that the DOX-loaded particles exhibited comparable antitumor activity with free DOX towards HeLa cells.
机译：设计了一种使用乙缩醛右旋糖酐作为阀门的pH敏感药物释放系统，以操纵细胞内抗癌药物的智能释放。通过点击反应将右旋糖酐接枝到MSN的外部，然后进行乙缩醛化以生成MSN-Dex-Ac的最终载体。疏水的Dex-Ac可以充当MSN表面上的阀门，以阻止MSN孔内截留的药物。当在酸性条件下模拟内体/溶酶体区室的微环境时，可以通过缩醛水解打开阀门以将缩醛化的葡聚糖恢复到其亲水状态，从而快速释放药物。体外药物释放曲线清楚地表明，DOX释放在阀门的pH值为7.4的情况下受到限制，而在酸性条件下则加速释放。通过共聚焦激光扫描显微镜（CLSM）观察到快速的内吞作用和细胞内DOX释放。细胞毒性评价显示与载体具有良好的生物相容性。体外MTT分析表明，负载DOX的颗粒与HeLa细胞的游离DOX表现出相当的抗肿瘤活性。

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