具有“差别性疏水组分”的UCST型双亲嵌段聚合物自组装研究

Because of the complicated requirements of the potential applications in the controllable loading and release area, such as drug delivery systems and as carriers in gene therapy, the amphiphilic polymer micelles should have the characteristics of hierarchical self-assembly with disparate hydrophobic subdomains. And according to the formation mode of disparate hydrophobic subdomains, it can be divided into three strategies of "Stimulus Transformation", "Component Difference" and "Site Control". And in this proposal, the "Site Control" strategy is chosen to develop the novel hierarchical self-assembly system based on the amphiphilic UCST block polymers with "Disparate Hydrophobic Components". It is designed to prepare the UCST hydrophilic chains with statistically distributed hydrophobic components by ATRP random polymerization, and then the hydrophobic segments are to be introduced by ATRP block polymerization; to study the influence of the structure parameters of the amphiphilic polymers, such as the monomer ratio, the structure feature of "Disparate Hydrophobic Components", and also the self-assembly conditions on the characteristic nano-structure of the polymer micelles, especially the disparate hydrophobic subdomains within the polymer micelles; to find the key between the controllability and reversibility of the dynamic distributions of the disparate hydrophobic subdomain and the polymer structure parameters, and also the temperature stimulus conditions; and at final to devote to expanding their application in the controllable loading and release areas.

为适应药物控释、基因治疗等在复杂环境下的应用要求，双亲性聚合物胶束应具有差别性疏水亚畴等异构分级自组装特征。而依据差别性疏水亚畴的引入方式，其实现方法可以分为"刺激转变"、"组分差异"和"位点控制"等策略。本项目拟采用"位点控制"策略，通过ATRP无规聚合制备疏水组分统计性分布的UCST型亲水链，进一步通过ATRP嵌段聚合引入疏水链段，从而获得具有"差别性疏水组分"的UCST型双亲嵌段聚合物；探究亲疏水组分比、"差别性疏水组分"结构特征、自组装条件等因素对聚合物胶束结构的影响规律，阐明差别性疏水亚畴的组装机制；建立聚合物结构参数、温度刺激条件等与差别性疏水亚畴动态分布特征的调控性与可逆性之间的内在关联；并致力于拓展其在负载-控制释放领域的应用与功能增强。

为适应药物控释、基因治疗等在复杂环境下的应用要求，课题组制备了含有香豆素、蒽两种可光交联基元的双亲聚合物、利用蒽与马来酰亚胺(OM)的Diels-Alder加成反应建立差别性交联体系，通过OM对香豆素、蒽基元荧光淬灭差异性，对OM在胶束间的转移平衡进行跟踪；利用可逆光二聚型香豆素、光解离型NO弱键，构建光反应差别性疏水组分基双亲聚合物，并利用365/254 nm组合光照进行聚合物胶束的形貌调控，进一步实现组合光照法调控DOX药物分子的光致释放；通过引入新型硼酸酯型温敏基元、或者构建主链型超支化聚合物制备了新型温敏聚合物；通过将邻硝基苄醇与苯硼酸酯有机结合，研究了新型苯硼酸酯基光解离聚合物的光刺激解离性能及其药物负载释放性能。以上研究工作共在Macromol. Rapid Commun.、Langmuir等期刊发表SCI论文12篇。