Development of Long-Circulating Zwitterionic Cross-Linked Micelles for Active-Targeted Drug Delivery
Development of Long-Circulating Zwitterionic Cross-Linked Micelles for Active-Targeted Drug Delivery
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用于活性靶向药物递送的长循环两性离子交联胶束的开发
DOI：
10.1021/acs.biomac.6b00168
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发表时间：
2016-06-01
影响因子：
6.2
通讯作者：
Chen, Shengfu
中科院分区：
文献类型：
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作者：
Lin, Weifeng;Ma, Guanglong;Chen, Shengfu
血液稳定性、主动靶向性和药物控制释放是设计理想药物载体的最重要特征。在这里，我们展示了一种基于五嵌段共聚物的两性可生物降解交联胶束，该胶束以聚(甲基丙烯酸羧基甜菜碱)为亲水链段，以聚己内酯为生物可降解疏水链段，以聚(S-O-羟乙基-O-二硫代碳酸乙酯)嵌段为硫醇保护链段进行交联，以环状精氨酸-甘氨酸-天冬氨酸-D-酪氨酸[c(RGDyK)]为靶向配体。结果表明，该胶束在高稀释度和50%胎牛血清中具有良好的胶体稳定性。体外释药实验显示生理条件下药物不发生突释，但在模拟肿瘤组织环境下可加速药物释放。体内试验表明，与游离药物相比，载药胶束延长了半衰期，提高了治疗效率，降低了心脏毒性和生物毒性。综上所述，重新植入的c(RGDyK)修饰的两性界面交联型胶束已经成为一个吸引人的癌症治疗平台。
Blood stability, active targeting, and controlled drug release are the most important features to design desirable drug carriers. Here, we demonstrate a zwitterionic biodegradable cross-linked micelle based on a penta-block copolymer, which utilizes poly(carboxybetaine methacrylate) as hydrophilic segment, poly(epsilon-caprolactone) as biodegradable hydrophobic segment, poly(S-2-hydroxyethyl-O-ethyl dithiocarbonate methacrylate) (PSODMA) block as thiol protecting segment for cross-linking, and cyclic Arg-Gly-Asp-D-Tyr-Lys [c(RGDyK)] as targeting ligand. As a result, this micelle possessed excellent colloidal stability at high dilution and in 50% fetal bovine serum. In =vitro drug release experiment showed no burst release under physiological conditions but accelerated drug release in mimicking tumor tissue environment. In vivo tests showed that the drug-loaded micelles had prolonged half-life in -bloodstream, enhanced therapeutic efficiency, and reduced cardiac toxicity and biotoxicity compared with free drug formulation. Taken together, the repotted c(RGDyK)-modified zwitterionic interfacially cross-linked micelle has.emerged as an appealing platform for cancer therapy