中文摘要：

制备了一种在疏水段带有侧基叠氮官能团的两亲性pH敏感的聚合物——聚己内酯-聚（甲基丙烯酸二乙氨基乙酯-磺酸甜菜碱）（（PCL-ACL）-PDEAS）;同时合成了两端带有炔基中间带有二硫键的交联剂,用红外、核磁表征了目标分子.通过两亲性高分子自组装形成胶束,并通过点击化学反应获得了核交联的胶束.通过动态光散射测定粒径,胶束酸碱滴定表征胶束的pH敏感性,还原条件下释放药物的速度,对比了非交联胶束和交联胶束的性质.结果表明,交联胶束在正常生理条件下的释放速度比未交联胶束更慢;而在有DTT的存在条件下,交联胶束由于二硫键断裂,释放速率明显加快.因此,核交联载药胶束有可能响应肿瘤的微环境实现靶向释放.

英文摘要：

Polymeric micelles after cross-linking can be overcome dissociation over dilution. In order to obtain cross-linked micelles, a novel pH-responsive copolymer, P（CL-ACL）-PDEAS, namely, poly（e-caprolactone/a- azidecaprolactone）-b-poly（N,-diethylaminoethylmethacrylate）-r-poly（N-（3-sulfopropyl）-N-methacy-loxyethy-N, N-diethylammoniumbetaine） was synthesized with azide groups in the hydrophobic block. A cross-linker, 2,2＂-bi（2＂-acetylene ethyl formate） amide ethyl disulfide, was also synthesized. The synthesis process of P（CL-ACL）-PDEAS included a combination of ring-open polymerization of caprolactone monomers, replacement and transformation of end functional groups, atom transfer radical of DEA monomers and sulfonation of DEA groups. The successful synthesis of the copolymer and the cross-linker were confirmed by nuclear magnetic resonance, Fourier transform infraredand elemental analysis. P（CL-ACL）-PDEAS was used to form polymer micelles by self-assembly. The cross-linked micelles were obtained through ＂click＂ chemistry by adding the cross-linker and catalyst during the process of micelle formation. Laser particle size analyzer （DLS） and fluorescence spectrophotometer were used to characterize the properties of the micelles. As a result, the sizes of the uncross-linked micelles and cross-linked micelles were 97.34 and 121.8 nm, respectively, and unimodal size distribution was observed for both types of the micelles. However, after 1000 fold dilution, the size of the cross-linked micelles and their unimodal distribution remained, while the size of the uncross-linked micelles increased greatly and the size distribution became dual. This meant that the cross-linked micelles were more stable In addition, acid-base titration test showed that both types of the micelles were pH-sensitive. Drug loading and release experiment were carried out using DOX as drug model. The drug loading content and the drug loading efficiency were similar for both types of the micelles. Finally, drug