抗肿瘤纳米药物的设计与挑战  

Design and challenge of cancer nanomedicine

作　　者：刘婧[1] 胡豆豆[1] 周泉[1] 申有青[1] Jing Liu;Doudou Hu;Quan Zhou;Youqing Shen(Center for Bionanoengineering,College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China)

机构地区：[1]浙江大学化学工程与生物工程学院生物纳米工程中心

出　　处：《中国科学：化学》2019年第9期1192-1202,共11页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:U1501243,21704090,51833008)资助项目

摘　　要：抗肿瘤纳米药物因能缓解传统小分子化疗药的全身毒性而进入临床应用.但目前研究的多数抗肿瘤纳米药物未能显著提高肿瘤治疗效果,因而止步于临床前或早期临床研究,如何显著提高疗效已成为下一代抗肿瘤纳米药物亟需解决的关键问题.分析体内肿瘤靶向过程可知,静脉注射的纳米药物需经过体内血液循环(C)、肿瘤蓄积(A)、肿瘤内渗透(P)、被细胞内吞(I)和在胞内释放(R)五步级联过程(即CAPIR cascade)才能在肿瘤细胞内发挥药效.使纳米药物的纳米特性包括稳定性(stability)、表面性质(surface properties)、尺寸(size)随输送过程各步的要求自主适应(self-adaptive)是纳米药物高效完成输送过程、获得高疗效的关键,但在肿瘤组织中渗透能力的天然缺失仍是纳米药物的"短板".在临床转化方面,体内安全性评价的复杂性和可控生产的复杂性是功能集成型纳米药物临床转化的瓶颈.同时,本文还介绍了我们最近提出的基于剥夺肿瘤信号分子的铜元素、使信号蛋白失活而达到抑瘤效果的新型类分子靶向药物.Anticancer nanomedicines can alleviate adverse effects of chemotherapeutic drugs and some are used in clinic, but they fail to improve the therapeutic efficacy. For rational design of next-generation highly effective cancer nanomedicines, this review analyzes the tumor-targeted drug delivery process of intravenously administered nanomedicines as a five-step CAPIR cascade, and further concludes that stability, surface and size nanoproperties(i.e., 3S nanoproperties) self-adaptive to the CAPIR steps via 3S nanoproperty transitions, which are the key to a nanomedicine to efficiently accomplish the delivery cascade and thus achieve high therapeutic efficacy. The reported strategies to realize the 3S nanoproeprty are summarized. Furthermore, the bottleneck of the delivery process, the inherent poor tumor penetration(low P) of nanomedicines and the methods and their limitations in improving P are summarized. Finally, the challenges of nanomedicine in clinical translation are discussed.

关 键 词：纳米药物 临床转化 肿瘤渗透 治疗性高分子 树枝状大分子 

分 类 号：R73[医药卫生—肿瘤]