多功能生物可降解聚合物纳米药物载体:设计合成及在肿瘤靶向治疗上的应用  

Multifunctional biodegradable polymeric nanocarriers: Design, synthesis, and applications in targeted tumor therapy

作　　者：邓超[1,2] 孟凤华[1,2] 程茹[1,2] 钟志远[1,2] 

机构地区：[1]苏州大学生物医用高分子材料重点实验室,苏州215123 [2]苏州大学材料与化学化工学部,苏州215123

出　　处：《科学通报》2015年第15期1339-1351,共13页Chinese Science Bulletin

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

摘　　要：生物可降解聚合物纳米载体具有良好的生物相容性、较长的体内循环时间、可靶向富集到肿瘤组织、在体内可降解等优越性能,是实现肿瘤靶向治疗最有前景的载体系统之一.多个基于生物可降解聚合物的纳米药物已投入市场或进入不同临床试验阶段.然而,纳米药物虽然有效降低了药物的毒副作用,却并没有显著提高肿瘤治疗效果.同时,纳米药物还存在体内稳定性差、药物易早释、肿瘤细胞内吞效率低、细胞内药物释放缓慢等问题.因此,提高纳米药物疗效的新策略成为国际研究的前沿和热点.本文综述了近年来本课题组及国内外学者在构建多功能生物可降解聚合物纳米载体和肿瘤靶向治疗上的研究进展.本文重点介绍了以下4个方面:(1)化学或物理交联稳定的生物可降解聚合物纳米载体,有效提高了纳米药物的体内稳定性,抑制药物早释,增强肿瘤靶向性能;(2)生物响应性生物可降解聚合物纳米载体,实现了抗癌药物在肿瘤组织和肿瘤细胞内的快速高效释放;(3)刺激敏感可逆交联的生物可降解纳米载体,巧妙解决了聚合物纳米载体在血液循环时需具有高稳定性、而在肿瘤细胞内需快速高效释放药物的矛盾;(4)靶向肿瘤的生物可降解聚合物纳米载体,促进了纳米药物在肿瘤组织处的滞留,增强纳米药物的内吞效率和肿瘤细胞内的富集.我们相信多功能聚合物纳米药物经过缜密设计、精确制备和系统研发,将会陆续进入临床应用并在肿瘤靶向治疗中发挥重要作用.Biodegradable polymeric nanocarriers have emerged as one of the most promising platforms for targeted tumor therapy owing to their excellent biocompatibility, prolonged circulation time, enhanced accumulation in tumors, and in vivo biodegradability. Remarkably, several anticancer nanomedicines based on biodegradable polymeric nanocarriers showed clear advantages, including decreased side effects and improved drug tolerance, and have advanced to clinical practices or clinical trials. However, the therapeutic outcomes are far from optimal, owing to poor in vivo stability, low tumor targetability, inefficient cellular uptake, and slow intracellular drug release, etc. Thus, the development of new strategies to improve the therapeutic efficiency of polymeric nanomedicines is of great interest. This review highlights the recent developments made by our group and others in multifunctional biodegradable polymeric nanocarriers for safe and efficient cancer chemotherapy. In particular, we will present the following four polymeric nanoscale systems： （i） chemically or physically crosslinked biodegradable polymeric nanocarriers that display markedly improved stability and tumor targetability while prohibiting drug leakage; （ii） bio-responsive, biodegradable polymeric nanocarriers that enhance tumor cell uptake via reversal of the stealth effect in response to the tumor microenvironment or rapidly and efficiently releasing drugs into the tumor tissue and/or inside the tumor cells; （iii） stimuli-responsive crosslinked biodegradable polymeric nanocarriers that elegantly address the extracellular stability and intracellular drug release dilemma; and （iv） tumor-targeted biodegradable polymeric nanocarriers that enhance drug retention in the tumor and facilitate tumor cell uptake of nanomedicines. Finally, the pros and cons of current multifunctional polymeric nanosystems are discussed. We are convinced that, with rationale design, precision preparation, and systemic research and development, various multifunction

关 键 词：纳米载体 抗癌药物 药物控制释放 靶向释放 肿瘤治疗 

分 类 号：TQ460.1[化学工程—制药化工] O631.3[理学—高分子化学]