Cylindrical polymer brushes-anisotropic unimolecular micelle drug delivery system for enhancing the effectiveness of chemotherapy  

作　　者：Shuang Bai Die Jia Xianbin Ma Mengyun Liang Peng Xue Yuejun Kang Zhigang Xu 

机构地区：[1]Key Laboratory of Luminescence Analysis and Molecular Sensing(Southwest University),Ministry of Education,School of Materials and Energy,Southwest University,Chongqing,400715,PR China [2]State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai,200438,China [3]Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices,Southwest University,Chongqing,400715,PR China

出　　处：《Bioactive Materials》2021年第9期2894-2904,共11页生物活性材料（英文）

基　　金：This work was financially supported by National Natural Science Foundation of China(51703187,31671037);the Basic and Frontier Research Project of Chongqing(cstc2018jcyjAX0104).

摘　　要：Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements,and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index.However,the majority of the polymer delivery systems are designed to be simple spherical nanostructures.To explore morphology/size-oriented delivery performance optimization,here,we synthesized three novel cylindrical polymer brushes(CPBs)by atom transfer radical polymerization(ATRP),which were cellulose-g-(CPT-b-OEGMA)(CCO)with different lengths(~86,~40,and~21 nm).The CPBs are composed of bio-degradable cellulose as the carrier,poly(ethylene glycol)methyl ether methacrylate(OEGMA)as hydrophily block,and glutathione(GSH)-responsive hydrophobic camptothecin(CPT)monomer as loaded anticancer drug.By controlling the chain length of the initiator,three kinds of polymeric prodrugs with different lengths(CCO-1,CCO-2,and CCO-3)could be self-organized into unimolecular micelles in water.We carried out comparative studies of three polymers,whose results verified that the shorter CPBs exhibited higher drug release efficiency,more cellular uptake,and enhanced tumor permeability,accompanied by shortened blood circulation time and lower tumor accumulation.As evidenced by in vivo experiments,the shorter CPBs exhibited higher anti-tumor efficiency,revealing that the size advantage has a higher priority than the anisotropic structure advantage.This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy.

关 键 词：Cylindrical polymer brushes Unimolecular micelles PRODRUG Reduction-responsive Cancer therapy 

分 类 号：R730.5[医药卫生—肿瘤]