生物还原敏感可降解聚合物纳米载体的构建与应用  

Bioreducible Biodegradable Polymeric Nanocarriers:Construction and Applications

作　　者：邓超[1] 孟凤华[1] 程茹[1] 张建[1] 钟志远[1] 

机构地区：[1]江苏省先进功能高分子材料设计及应用重点实验室苏州大学材料与化学化工学部苏州大学生物医用高分子材料重点实验室,苏州215123

出　　处：《高分子通报》2015年第10期42-50,共9页Polymer Bulletin

基　　金：国家自然科学基金(基金号51273137和51473110);国家杰出青年科学基金(基金号51225302);江苏高校优势学科建设工程资助项目

摘　　要：生物可降解聚合物纳米载体具有较长的体内循环时间、能靶向并富集到肿瘤组织、降低毒副作用、增加药物利用率以及在体内可降解等优越性能，已成为实现肿瘤靶向治疗最有前景的载体系统之一。但是，f临床试验结果表明，聚合物纳米药物的治疗效果与人们的预期相差甚远，其中一个重要原因是纳米药物在靶点处药物释放少且缓慢。因此，开发智能型纳米载体使其在到达靶点后即迅速释放包裹的药物成为近年的研究热点。肿瘤组织，尤其是肿瘤细胞内的谷胱甘肽（glutathione，GSH）浓度较高（2～10mM），大约是体液和细胞外基质的1～100倍（2～10μM）。基于肿瘤独特的还原势能，人们构建了各种不同类型的还原敏感聚合物纳米载体，实现抗癌药物在肿瘤组织和肿瘤细胞内的快速高效释放。生物还原敏感聚合物纳米载体具有以下特点：（1）在生理条件下稳定；（2）对肿瘤细胞内还原环境响应快，触发药物快速释放；（3）无需任何外在刺激装置，简单方便。本文将结合我们课题组的工作介绍各种还原敏感可降解聚合物纳米载体的构建和应用，主要包括还原敏感生物可降解聚合物胶束、囊泡、纳米凝胶等。Biodegradable polymeric nanocarriers have emerged as one of the most promising platforms for targeted tumor therapy owing to their prolonged circulation time, enhanced accumulation in tumors, decreased adverse effects, improved drug bioavailability, and in vivo biodegradability. However, their therapeutic outcomes are far from optimal partially owing to inefficient and slow intracellular release of drugs at pathological sites. The development of stimuli-responsive nanocarriers that achieve fast drug release at the target site has received great interests. Notably, glutathione （GSH） concentration in tumor tissue and especially inside tumor cells varies from 2 to 10mM, which is about 100 - 1000 times higher than that in body fluids and extracellular matrices （2- 10μM）. Taking advantage of the high reducing potential, various reduction-sensitive polymeric nanocarriers have been fabricated for triggered anticancer drug release in tumor tissues and tumor cells. These reduction-sensitive nanocarriers have displayed several unique merits： （1） they have good stability under physiological conditions; （2） they show fast response to intracellular reducing environment, resulting in efficient intraeellular drug release; （3） no extra instrument is required. This review highlights the construction and applications of various bioreducible biodegradable polymeric nanocarriers, including bioreducible biodegradable polymeric micelles, polymersomes, and nanogels.

关 键 词：还原敏感 聚合物胶束 聚合物囊泡 纳米凝胶 可逆交联 靶向释放 肿瘤治疗 

分 类 号：O631.11[理学—高分子化学] TQ460.1[理学—化学]