响应性支化聚合物的合成、组装及其生物医药应用

Synthesis and Self-assembly of Responsive Branched Polymers and Their Biomedical Applications

环境响应性超支化聚合物作为超支化聚合物中一类智能聚合物,备受研究者关注,已被广泛用于生物医药领域.本文主要介绍了本课题组在响应性支化聚合物的合成、组装及其生物医药应用方面的部分研究工作.主要包括以下三方面的内容:第一部分介绍了酸响应性支化聚合物、温敏性支化聚合物、还原响应性支化聚合物和光响应性支化聚合物的合成;第二部分介绍了含有二硫键的温敏性超支化聚合物在温度诱导下的自组装及自交联反应制备纳米凝胶、纳米胶囊和交联复合囊泡;第三部分介绍了响应性支化聚合物在药物传递和基因传递方面的应用.

Stimuli-responsive hyperbranched polymers have attracted increasing attention due to their great advantages in biomedical applications. This review highlights their synthesis and self-assembly as well as their biomedical applications. The first part of this review focuses on the synthesis of acid-responsive, temperature-responsive, redox-responsive and photo-responsive branched polymers. These responsive branched polymers are synthesized via reversible addition-fragmentation chain transfer（RAFT） polymerization or Michael addition polymerization. The second part of this review focuses on the preparation of nanogels/microgels, nanocapsules and cross-linked large compound vesicles（LCVs） via temperature-induced self-assembly and self-crosslinking of temperature-responsive branched polymers. These polymers aggregate and self-assemble into nanoparticles or vesicles above their lower critical solution temperature（LCST）, the formed nanoparticles or vesicles self-crosslink into nanogels/microgels, nanocapsules or cross-linked LCVs via intermolecular disulfide exchange reaction. The nanogels/microgels are prepared in aqueous solution, and their sizes can be tuned by adjusting the polymer concentration. The nanocapsules and cross-linked LCVs are prepared in emulsion droplets, and their sizes can be tuned by changing the amount of emulsifier. These biocompatible and bioreducible assembled nanostructures have demonstrated great potential to be used as proteins and DNA delivery vectors. The third part of this paper focuses on the applications of the responsive branched polymers in drug and gene delivery. In drug delivery, the hollow voids in the branched polymers architecture can be used to load drugs. However, this loading strategy easily results in leakage of drugs. Based on the abundant functional groups on the branched polymers, drugs can be linked onto the polymers via a labile linkage which can be cleaved under environmental stimuli. In gene delivery, positively charged branched polymer can condense DNA better than their linear counterparts, forming more stable polyplex, and the stimuli-responsiveness of the branched polymers can facilitate the release of loaded DNA.