Du Zhengzhen, Zhang Yan, Lang Meidong
Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
J Mater Sci Mater Med. 2015 Apr;26(4):171. doi: 10.1007/s10856-015-5499-y. Epub 2015 Mar 25.
This study focuses on the synthesis of Pluronic-b-poly(ε-caprolactone) bearing benzyl-oxycarbonylmethyl and carboxylic groups and the comparative study to investigate the influence of the different pendant groups on the cellular behavior. The functionalized Pluronic-b-poly(ε-caprolactone) bearing two kinds of pendant groups are synthesized via ring-opening polymerization of ε-caprolactone and 6-(benzyl-oxycarbonyl methyl)-ε-caprolactone and followed by deprotection respectively. The structure of the copolymers is confirmed and the polymeric micelles are formed by an emulsion/solvent evaporation technique. The critical micelle concentrations are improved compared with Pluronic F127, the morphologies of the micelles are spherical with the diameter on nano scale and good colloidal stability. The copolymers have good cytocompatibility and the comparative study reveals that cellular internalization, digesting by lysosome and intracellular distribution are affected by the pendant groups, moreover, the endocytosis pathway is determined by the pendant groups. Therefore, the definite internalization mechanism is beneficial for the design of polymeric micellar carriers to achieve intra- or extracellular modes of drug delivery and provide better access to either cell membrane or intracellular organelles.
本研究聚焦于带有苄氧羰基甲基和羧基的聚环氧乙烷-聚（ε-己内酯）的合成以及比较研究，以探究不同侧基对细胞行为的影响。通过ε-己内酯和6-（苄氧羰基甲基）-ε-己内酯的开环聚合反应，随后分别进行脱保护反应，合成了带有两种侧基的功能化聚环氧乙烷-聚（ε-己内酯）。确认了共聚物的结构，并通过乳液/溶剂蒸发技术形成了聚合物胶束。与普朗尼克F127相比，临界胶束浓度有所提高，胶束形态为纳米级球形且具有良好的胶体稳定性。共聚物具有良好的细胞相容性，比较研究表明，细胞内化、溶酶体消化和细胞内分布受侧基影响，此外，内吞途径由侧基决定。因此，明确的内化机制有利于设计聚合物胶束载体，以实现细胞内或细胞外给药模式，并更好地作用于细胞膜或细胞内细胞器。
