Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
J Phys Chem B. 2013 Feb 7;117(5):1261-8. doi: 10.1021/jp310677p. Epub 2013 Jan 23.
Smart pH-responsive polymeric micelles have attracted much attention as one of the most promising drug delivery candidates. In this paper, a different substitution of deoxycholic acid (DCA) and folic acid (FA) comodified hydroxypropyl chitosans (HPCHS) were synthesized for doxorubicin (DOX) targeted delivery and controllable release. The results indicate that the DOX-release behavior is pH-responsive and closely related with the grafting proportions of the two hydrophobic ingredients. The pH-responsive mechanism for the optimized (6%DCA)-HPCHS-(0.1%FA) was suggested, resulting from a synergistic effect of gradual hydrolysis of the amido bond and electrostatic repulsion between the subsequently protonated DOX and the amino residue of the chitosan backbone under a cancerous microenvironment. Moreover, the DOX/(6%DCA)-HPCHS-(0.1%FA) micelle as a promising targeted drug delivery system in cancer therapy was evaluated by cell growth inhibition assays and confocal laser microscopy in vitro. The results clearly demonstrate a controlled release of its cargo and promoted curative efficacy of DOX.
智能 pH 响应型聚合物胶束作为最有前途的药物输送候选物之一引起了广泛关注。在本文中，我们合成了不同取代的脱氧胆酸（DCA）和叶酸（FA）共修饰的羟丙基壳聚糖（HPCHS），用于阿霉素（DOX）的靶向输送和可控释放。结果表明，DOX 的释放行为是 pH 响应的，与两种疏水性成分的接枝比例密切相关。优化的（6%DCA）-HPCHS-（0.1%FA）的 pH 响应机制归因于酰胺键的逐步水解和在癌症微环境下，随后质子化的 DOX 与壳聚糖主链上的氨基残基之间的静电排斥之间的协同作用。此外，通过体外细胞生长抑制实验和共聚焦激光显微镜评估了 DOX/（6%DCA）-HPCHS-（0.1%FA）胶束作为癌症治疗中一种有前途的靶向药物输送系统。结果清楚地表明其货物的控制释放和提高了 DOX 的治疗效果。
