Construction of serum resistant micelles based on heparosan for targeted cancer therapy
Construction of serum resistant micelles based on heparosan for targeted cancer therapy
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基于heparosan构建抗血清胶束用于癌症靶向治疗
DOI：
10.1016/j.carbpol.2014.03.084
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发表时间：
2014-09-22
影响因子：
11.2
通讯作者：
Chen, Jing-Hua
中科院分区：
文献类型：
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作者：
Chen, Jing-Xiao;Zhang, Miao;Chen, Jing-Hua
本文报道了一种以肝素原和脱氧胆酸（DOCA）偶联物（HD）为药物载体的新型胶束。由于表面带负电荷，该胶束能抵抗血清吸附，表现出良好的稳定性。荧光观察证实，它能够有效地将模型疏水药物阿霉素（DOX）递送到HeLa细胞中。载药胶束在pH7.4时表现出缓释行为，在pH5.0或在肿瘤细胞中过表达的β-葡萄糖醛酸酶存在下表现出加速释放行为。体外细胞毒性实验表明，载阿霉素胶束对HeLa细胞的半数抑制浓度（IC 50）远低于COS 7细胞，对肿瘤细胞和正常细胞的治疗效果有显著差异。结合肝素前体良好的生物相容性和生物降解性，该胶束有望在临床靶向给药中应用。(C)2014爱思唯尔有限公司版权所有。
A novel micelle based on heparosan and deoxycholic acid (DOCA) conjugate (HD) as drug carrier was reported here. As the surface was negatively charged, this micelle could resist serum adsorption, showing favorable stability. Moreover, fluorescence observation confirmed that it was able to deliver model hydrophobic drug doxorubicin (DOX) into HeLa cells efficiently. The DOX-loaded micelles showed sustained release behavior at pH 7.4, and accelerated release behavior at pH 5.0 or in the presence of P-glucuronidase, which over-expressed in tumor cells. In vitro cytotoxicity assay demonstrated that the half-maximal inhibitory concentration (IC50) of DOX-loaded micelles against HeLa cells was much lower than that of COS7 cells, showing significant therapeutic distinction between tumor cells and normal cells. Combining with the good biocompatibility and biodegradability of heparosan, this micelle may be promising in clinical application for targeted drug delivery. (C) 2014 Elsevier Ltd. All rights reserved.