还原敏感性两亲性环状刷形共聚物的合成及性能

Preparation and Property of Reduction-Sensitive Amphiphilic Cyclic Brush Copolymer

采用点击化学、开环聚合、酯化反应和原子转移自由基聚合反应,制备了还原敏感性两亲性环状刷形共聚物P(HEMA-g-PCL-SS-POEGMA)。通过核磁共振和凝胶渗透色谱对共聚物结构进行了表征;利用荧光分光光度计测试了聚合物临界聚集浓度(CAC),结果表明共聚物在水溶液中能保持结构稳定;利用动态光散射仪测试了共聚物在还原剂二硫苏糖醇(DTT)存在下的粒径变化;通过透射电镜观察了共聚物与还原剂共培养不同时间的粒径变化图像;通过共聚物对体外抗癌药物阿霉素(DOX)的负载和释放实验,说明共聚物结构受DTT影响发生了去稳定化;通过细胞吞噬实验,得出共聚物载药胶束可有效被HeLa细胞内吞,并携带DOX进入到细胞质中。

A reduction-sensitive amphiphilic cyclic brush polymer,poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate))(P(HEMA-g-PCL18-POEGMA)50)with reducible block junctions bridging the hydrophobic PCL middle layer and hydrophilic POEGMA outer corona was designed and synthesized successfully via a“grafting from”approach by click chemistry,ring-opening polymerization(ROP),sequential esterification and atom transfer radical polymerization(ATRP)from cyclic multimacroinitiator PHEMA.The structures of polymers were characterized by 1 H-NMR spectrometer and SEC-MALLS.The critical aggregation concentration(CAC)results reveal that P(HEMA-g-PCL18-SS-POEGMA30)50 has the highest stability.The dynamic light scatting(DLS)determination reveals that the particle size changes in the presence of the reductant dithiothreitol(DTT).Transmission electron microscope(TEM)results demonstrate the morphology of the copolymer co-cultured with the reductant at different time.A further evaluation of the delivery efficacy by in vitro drug release and in vitro cytotoxicity study confirms a greater cumulative drug release from the doxorubicin(DOX)-loaded reduction-sensitive micelles of cyclic brush copolymers P(HEMA-g-PCL18-SS-POEGMA30)50 in the presence of 10 mmol/L DTT and higher therapeutic efficacy of this formulation relative to the reduction-insensitive counterparts.