刺激响应变形纳米载药体系的构建及性能研究

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。

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

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.