Enzyme/pH-sensitive dendritic polymer-DOX conjugate for cancer treatment

作     者：Kai Chen Shuangsi Liao Shiwei Guo Hu Zhang Hao Cai Qiyong Gong Zhongwei Gu Kui Luo 陈凯;廖爽斯;郭仕伟;张虎;蔡豪;龚启勇;顾忠伟;罗奎

作者机构：National Engineering Research Center for BiomaterialsSichuan UniversityChengdu 610064China Huaxi MR Research Center（HMRRC）Department of RadiologyWest China HospitalSichuan UniversityChengdu 610041China College of Life SciencesSichuan UniversityChengdu 610064China School of Chemical EngineeringThe University of AdelaideSA 5005Australia 

基　　金：supported by the National Natural Science Foundation of China (51673127 and 8162103) International Science and Technology Cooperation Program of China (2015DFE52780 and 81220108013) International Science and Technology Cooperation Program of Chengdu (2016-GH03-00005-HZ) 

出 版 物：《Science China Materials》 (中国科学（材料科学（英文版）)

年 卷 期：2018年第61卷第11期

页      码：1462-1474页

摘      要：It is in a great demand to design a biodegradable, tumor microenvironment-sensitive drug delivery system to achieve safe and highly efficacious treatment of ***, a novel pH/enzyme sensitive dendritic pdi HPMADOX conjugate was designed. di HPMA dendritic copolymer with GFLG segments in the branches which are sensitive to the intracellular enzyme of the tumor was prepared through RAFT polymerization. DOX was attached to dendritic di HPMA polymer through a pH-sensitive hydrazone bond. The dendritic pdi HPMA-DOX conjugate self-assembled into nanoparticles with an ideal spherical shape at a mean size of 103 nm. The DOX attached to the polymeric carrier was released in an acidic environment, and the GFLG linker for synthesizing the dendritic vehicle with a high molecular weight（M_W, 220 kDa） was cleaved to release low MWsegments（〈40 kDa） in the presence of cathepsin B. The dendritic polymeric conjugate was internalized via an endocytic pathway, and then released the anticancer drug, which led to significant cytotoxicity for tumors. The blood circulation time was profoundly prolonged, resulting in high accumulation of DOX into tumors. In vivo anti-tumor experiments with 4 T1 tumor bearing mice demonstrated that the conjugate had a better antitumor efficacy in comparison with free DOX. Additionally, body weight measurements and histological examinations indicated that the conjugate showed low toxicities to normal tissues. This dendritic polymeric drug carrier in a response to intracellular enzyme and acidic pH of tumor tissue or cells holds great promise in tumor-targeted therapy.

主 题 词：dendritic polymer conjugate stimuli-responsive biodegradability biocompatibility anti-tumor therapy 

学科分类：1002[医学-临床医学类] 100214[100214] 10[医学] 

核心收录：

D　O　I：10.1007/s40843-018-9277-8

馆 藏 号：203297575...