pH和还原双重敏感性超支化纳米胶束的制备及其释药性能

Preparation and Drug Release Properties of pH/Redox-Responsive Hyperbranched Nano Micelles

将聚乙二醇二缩水甘油醚（PEGDGE）与胱胺（Cys）置于水溶液中，通过亲核开环反应制备出超支化聚合物，并自组装形成多核-壳结构的纳米胶束，再通过甲氨蝶呤（MTX）与纳米胶束间的疏水作用制备出载药胶束。用FT-IR、^1H-NMR、DLS、SEM等方法对聚合物结构和胶束粒径与形貌进行表征，采用噻唑蓝（MTT）法测试纳米胶束和载药胶束的细胞毒性。结果表明：聚合物经过透析纯化后自组装形成纳米胶束，其粒径约为100 nm，呈均一球形；载药胶束对MTX的载药率为10.32%；当载药胶束处于模拟肿瘤环境中时，酸性和还原性条件可刺激药物释放。细胞毒性实验表明，纳米胶束具有优良的生物相容性；载药胶束具有较强的抗肿瘤活性。

Hyperbranched nano micelles with a multi-core-shell structure were prepared via the nucleophilic ring-opening reaction of poly（ethylene glycol） diglycidyl ether （PEGDGE） and cystamine （Cys） in aqueous solution.The drug methotrexate （MTX） was loaded into nano micelles through hydrophobic interactions between MTX and nano micelles to form drug-loaded micelles.The chemical structure and morphology of the micelles were characterized by FT-IR,^1H-NMR,DLS and SEM.The cytotoxicity of nano and MTX-loaded micelles were studied by Methyl Thiazolyl Tetrazolium（MTT） assays.Results showed that the hyperbranched nano micelles had spheric morphology with an average diameter of 100 nm and narrow dispersity.MTX-loaded micelles had drug loading content of 10.32%.The release of MTX was stimuli-responsive under an acidic and reductive condition which simulated the intracellular environment of tumors.MTT assays demonstrated that nano micelles were highly biocompatible in vivo,while MTX-loaded micelles caused pronounced cytotoxic effects to Hela tumor cells.