单分子聚合物纳米材料的可控合成及生物应用

Controllable Synthesis and Biological Properties of Unimolecular Polymer Nanomaterials

现代有机化学和高分子化学的发展为我们提供了多种高效可控的合成手段,例如点击化学、原子转移自由基聚合、可逆加成-断裂链转移聚合、开环易位聚合等.综合利用这些合成手段,不同拓扑结构的单分子聚合物纳米材料可以被高效可控地合成.本文主要介绍我们课题组近几年利用可控合成策略制备的几种不同类型的单分子聚合物纳米材料(包括环糊精聚轮烷、树枝状聚合物、多臂聚合物和聚合物分子刷)以及利用这些高分子纳米材料的高度可控性,对其结构与生物性能之间构效关系的探索.

With the rapid development of modern organic chemistry and polymer chemistry, a variety of highly efficient and controllable synthetic methods have been discovered and applied extensively, such as click chemistry, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, and ring-opening metathesis polymerization. Their comprehensive application has realized the controlled preparation of unimolecular polymer nanomaterials with well-designed topological structures, including cyclodextrane polyrotaxanes, dendrimers, multiarm star-shaped polymers, wormlike polymer brushes, etc. Functioning as probes and drug carriers for disease diagnoses and treatments, respectively, these specifically fabricated materials are featured with such advantages as high designability, controllability, and stability of chemical structures, favorable reproducibility of pharmacokinetic and pharmacological profiles, great abundancy in reactive groups for multiple functionalization, and desirable ability to covalent-combine drugs for responsive targeted drug release. The highly controllable chemical structures of these unimolecular polymer nanomaterials make them the most suitable objects for studying the relationship between chemical and morphological structures and biological performance. Herein, the recent progress of our group is introduced, with specific focuses on the preparation of unimolecular polymer nanomaterials through controllable synthetic strategies, the precise control of their chemical structures and sizes, and the effect of their chemical structures and sizes on their in vitro and in vivo biological performance. The objectives of our research include cyclodextrane polyrotaxanes, dendrimers, multiarm star-shaped polymers, and wormlike polymer brushes, and their sizes range from several nanometers to dozens of nanometers. Based on our experiments, some important conclusions have been drawn as follows. Within the dimensional range between ten nanometers and dozens of nanometers, the size reduction of such nanomaterials favors higher cellular uptake, shorter blood circulation, as well as higher tumor accumulation and penetration. Besides, the nanomaterials with zwitterionic poly(carboxybetaine)(PCB) surface exhibit higher cellular uptake, longer blood circulation, and higher tumor accumulation and penetration than those with the poly(ethylene glycol)(PEG) surface do thanks to the surface-tethered phenylboronic acid groups. These results can be much conducive to the design of polymer nanocarriers for tumor diagnosis and therapy.