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  • 王梓姣,郭方方,刘 青,等.刺激响应变形纳米载药体系的构建及性能研究[J].同济大学学报(医学版),2020,41(1):33-40.    [点击复制]
  • WANG Zi-jiao,GUO Fang-fang,LIU Qing,et al.Construction and performance of deformable drug delivery nanosystem with tumor microenvironment responsiveness[J].同济大学学报(医学版),2020,41(1):33-40.   [点击复制]
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刺激响应变形纳米载药体系的构建及性能研究
王梓姣,郭方方,刘青,时东陆
0
(同济大学医学院,上海 200092)
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。
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
DOI:10.16118/j.1008-0392.2020.01.006
投稿时间:2019-04-12
基金项目:中央高校基本科研业务费专项资金(22120180131)
Construction and performance of deformable drug delivery nanosystem with tumor microenvironment responsiveness
WANG Zi-jiao,GUO Fang-fang,LIU Qing,SHI Dong-lu
(Tongji University School of Medicine, Shanghai 200092, China)
Abstract:
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 5nm and 13nm 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 50nm and 80nm, 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 32nm, 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.
Key words:  gold nanoparticle  triplex DNA  tumor microenvironment  drug delivery  deformable structure

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