酸和谷胱甘肽的双重响应性聚合物胶束负载光敏剂用于肿瘤细胞的光动力治疗  

Acid and GSH Dual-Stimuli Response Polymer Micelles Loaded Photosensitizers for Photodynamic Therapy of Tumor Cells

作　　者：王秋生 曹红亮 杲云 WANG Qiusheng;CAO Hongliang;GAO Yun(Shanghai Key Laboratory of Advanced Polymeric Materials,School of Meterials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学材料科学与工程学院上海市先进聚合物材料重点实验室

出　　处：《华东理工大学学报（自然科学版）》2019年第3期424-431,共8页Journal of East China University of Science and Technology

摘　　要：将大分子引发剂溴代聚乙二醇单甲醚(PEG2KBr)和酸响应的单体二(2-丙烯酰氧基乙氧基)-(4-甲氧基苯基)甲烷(ACD)通过逆向增强-原子转移自由基聚合(DE-ATRP)得到新型的两亲性嵌段共聚物 PEG-b-PACDs,再利用滴水法自组装形成纳米胶束及载有二氢卟吩 e6(Ce6)的纳米胶束。通过核磁共振氢谱(1H-NMR)、动态光散射(DLS)、透射电子显微镜(TEM)等对聚合物的结构及胶束粒径和形貌进行了测试表征,并采用噻唑蓝(MTT)法验证了载有 Ce6 的胶束对细胞的毒性。结果表明,聚合物可自组装成均一的球形胶束,负载Ce6后载药量可达到6.04%;在模拟肿瘤微环境的条件下,载药胶束具有酸、谷胱甘肽(GSH)两重响应性,并且有着良好的载药缓释性能;细胞毒性实验证明了该载药胶束对癌细胞具有很好的光动力治疗(PDT)效果。Amphiphilic block copolymer polyethylene glycol-b-di(2-acryloyloxy ethoxy-[4-methoxy-phenyl] methane)(PEG-b-PACDs) was successfully synthesized by deactivation enhanced atom transfer radical polymerization (DE-ATRP) with brominated polyethylene glycol (PEG2KBr) as a macromolecular initiator and di (2-acry-loyloxy ethoxy)-[4-methoxy-phenyl]methane as an acid-cleavable divinyl (ACD) monomers. The polymer was self-assembled by drip water method to form micelles, and the drug chlorin e6 (Ce6) was loaded into micelles to generate drug-loaded micelles. The structural characteristics of the polymer were analyzed by nuclear magnetic resonance hydrogen spectroscopy (1H-NMR). The polymer with acetal structure could be hydrolyzed to aldehydes and alcohols under acidic conditions. The polymer retains olefinic bond, thus had a novel glutathione (GSH) responsive through the Michael addition reaction between GSH and olefinic bond. The size and morphology of the self-assembled blank micelles and Ce6-loaded micelles were characterized by Dynamic Light Scattering (DLS) and transmission electron microscope (TEM), which showed that both blank micelles and Ce6-loaded micelles can form uniform spherical micelles. The drug loading content of Ce6-loaded micelles could reach 6.04%. The sustained release of Ce6 from Ce6-loaded micelles in vitro clearly showed that Ce6-loaded micelles exhibited dual-stimuli responses by acid and GSH leading to controlled drug release behavior. In addition, the cytotoxicity of the drug-loaded micelles was verified by 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The cytotoxicity experiments also demonstrated that the Ce6-loaded micelles had a good photodynamic therapy (PDT) effect on cancer cells.

关 键 词：逆向增强-原子转移自由基聚合 响应释放 光动力治疗 

分 类 号：O632.12[理学—高分子化学]