肿瘤微环境响应型的RNA药物递送系统的研究进展  

Research progress of tumor microenvironment-responsive RNA drug delivery systems

作　　者：卢安 王向宇 闫仪 王坚成[1] LU An;WANG Xiang-yu;YAN Yi;WANG Jian-cheng(School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京大学药学院,北京100191

出　　处：《药学学报》2022年第1期109-121,I0005,共14页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81773650,81973259,81690264);国家新药创制重大专项(2018ZX09721003-004).

摘　　要：肿瘤作为全球危害人类健康的重大疾病之一,亟需寻找更加安全高效的治疗方案。核糖核酸(ribonucleic acid,RNA)药物的基因疗法可以调节肿瘤相关基因的表达,已在临床前和临床试验中展示出良好的抗肿瘤治疗潜力。基于肿瘤组织在pH、特异性酶浓度或氧化还原梯度变化等微环境信号特征与正常组织存在差异性,各类微环境响应型纳米载体正在被研究开发用于递送RNA药物,实现对肿瘤组织与细胞的靶向递送,提高RNA药物的抗肿瘤疗效并且降低不良反应。本文综述了肿瘤微环境的病生理特征以及各类肿瘤微环境响应型载体策略,旨在为设计安全高效的RNA药物肿瘤靶向递送系统提供参考。Cancer is considered as one of the major diseases endangering human health in the world,it is urgent to find a safer and more efficient treatment for cancer therapy.Gene therapy with ribonucleic acid(RNA)drugs could regulate the expression of tumor related genes,and exhibit good anti-tumor therapeutic potential in preclinical and clinical trials.Based on the differences between tumor tissues and normal tissues in microenvironment signal characteristics such as pH,specific enzyme concentration or redox gradient,various microenvironment responsive nanocarriers had been studied and developed to deliver RNA drugs to tumor tissues and cells,improving the anti-tumor efficacy of RNA drugs and reducing toxic and side effects.This paper reviews the pathophysiological characteristics of tumor microenvironment and various strategies of tumor microenvironment responsive nanocarriers,in order to provide reference for the design of safe and efficient RNA drug delivery system for cancer therapy.

关 键 词：肿瘤微环境 药物递送系统 基因治疗 刺激响应型载体 纳米药物 

分 类 号：R943[医药卫生—药剂学]