Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel
Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel
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DOI：
10.1016/j.biomaterials.2011.11.022
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发表时间：
2012-03-01
期刊：
影响因子：
14
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Li, Jing;Huo, Meirong;Zhang, Qiang
基于氧化还原敏感的透明质酸 - 脱氧胆酸（HA - ss - DOCA）偶联物，成功开发了一种紫杉醇（PTX）的靶向细胞内递送系统。该偶联物在水性介质中自组装成纳米级胶束，对PTX表现出优异的载药能力（34.1%）和包封率（93.2%）。HA - ss - DOCA胶束在模拟正常生理条件下足够稳定，但在20 mM还原剂谷胱甘肽存在时会快速解聚。体外药物释放研究表明，载PTX的HA - ss - DOCA胶束在还原条件下实现了快速药物释放。荧光探针尼罗红的细胞内释放表明，HA - ss - DOCA胶束为货物快速转运到细胞质提供了一种有效方法。载PTX的HA - ss - DOCA胶束细胞毒性增强，进一步证实与不敏感的对照相比，这种敏感胶束在细胞内药物递送方面更有效。基于流式细胞术和共聚焦显微镜分析，观察结果显示HA - ss - DOCA胶束通过HA受体介导的内吞作用被人乳腺癌细胞（MDA - MB - 231）摄取。对荷瘤小鼠体内胶束的研究证实，HA - ss - DOCA胶束比不敏感的对照具有更高的肿瘤靶向能力。这些结果表明，氧化还原敏感的HA - ss - DOCA胶束作为亲脂性抗癌药物的靶向细胞内递送载体具有巨大潜力。（C）2011年由爱思唯尔有限公司出版
A targeted intracellular delivery system of paclitaxel (FIX) was successfully developed based on redox-sensitive hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates. The conjugates self-assembled into nano-size micelles in aqueous media and exhibited excellent drug-loading capacities (34.1%) and entrapment efficiency (93.2%) for FTX. HA-ss-DOCA micelles were sufficiently stable at simulated normal physiologic condition but fast disassembled in the presence of 20 mm reducing agent, glutathione. In vitro drug release studies showed that the FTX-loaded HA-ss-DOCA micelles accomplished rapid drug release under reducing condition. Intracellular release of fluorescent probe nile red indicated that HA-ss-DOCA micelles provide an effective approach for rapid transport of cargo into the cytoplasm. Enhanced cytotoxicity of FIX-loaded HA-ss-DOCA micelles further confirmed that the sensitive micelles are more potent for intracellular drug delivery as compared to the insensitive control. Based on flow cytometry and confocal microscopic analyses, observations revealed that HA-ss-DOCA micelles were taken up to human breast adenocarcinoma cells (MDA-MB-231) via HA-receptor mediated endocytosis. In vivo investigation of micelles in tumor-bearing mice confirmed that HA-ss-DOCA micelles possessed much higher tumor targeting capacity than the insensitive control. These results suggest that redox-sensitive HA-ss-DOCA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anticancer drugs. (C) 2011 Published by Elsevier Ltd.