刺激响应变形纳米载药体系的构建及性能研究  

Construction and performance of deformable drug delivery nanosystem with tumor microenvironment responsiveness

作　　者：王梓姣 郭方方[1] 刘青 时东陆[1] WANG Zi-jiao;GUO Fang-fang;LIU Qing;SHI Dong-lu(Tongji University School of Medicine,Shanghai 200092,China)

机构地区：[1]同济大学医学院

出　　处：《同济大学学报（医学版）》2020年第1期33-40,共8页Journal of Tongji University(Medical Science)

基　　金：中央高校基本科研业务费专项资金(22120180131)

摘　　要：目的构建肿瘤微环境响应释放的可变形金纳米颗粒载药体系。方法利用直径5、13nm两种尺寸的金纳米颗粒、pH敏感的三链体脱氧核糖核酸(triplex DNA)以及抗肿瘤药物多柔比星(doxorubicin hydrochloride, DOX),通过冷冻法组装出载药聚集体结构并对该体系的有效性进行表征。结果所组装的聚集体中有75%的颗粒的粒径(直径)在50~80nm,大小适宜,易于被细胞内吞,可有效载带药物,在pH=4.5时,载药聚集体发生解体,89.6%的颗粒直径为18~32nm,释放出相较于中性条件下3倍浓度的DOX(P<0.01)并对肿瘤细胞有明显杀伤效果。结论此可变形的金纳米载药聚集体结构成功的完成药物的载带与释放,达到了可控释药,降低正常组织损伤的目的,为新一代刺激响应型纳米载带系统地构建提供了新思路。Objective To design and construct a deformable drug-loading gold nanoparticle cluster structure which can respond to the acidic tumor microenvironment. Methods The gold nanoclusters were assembled by freezing method using 5 nm and 13 nm gold nanoparticles, pH-sensitive triplex DNA strands and anti-cancer drug doxorubicin. The formation of the nanocluster, its drug payload and responsive release were testified. Results The size of 75% gold nanoclusters ranged between 50 nm and 80 nm, which was suitable for endocytosis and exhibited controllable drug delivery. At pH 4.5, the gold nanoclusters returned to a dispersed state, the size of 89.6% particle was between 18 nm and 32 nm, releasing 3 times doxorubicin more than under neutral conditions(P<0.01). Conclusion The deformable gold nanoclusters have good drug release efficiency and stable deformation process. Thereby, it can achieve controlled release of drugs, reduce normal tissue damage, and provide a new generation of stimuli-responsive nanocarrier system.

关 键 词：金纳米颗粒 三链体脱氧核糖核酸 肿瘤微环境 药物输运 可变形结构 

分 类 号：R318.08[医药卫生—生物医学工程]