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(PEG2 KBr) 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.
引文
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