Synthesis of polypeptide bearing 1,4-dithiane pendants for ROS-responsive drug release

作     者：Tianhui Zhang Jiuxu Yao Jiamei Tian Mingxiao Deng Xiuli Zhuang Chunsheng Xiao Tianhui Zhang;Jiuxu Yao;Jiamei Tian;Mingxiao Deng;Xiuli Zhuang;Chunsheng Xiao

作者机构：Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of China.Hefei 230026China Department of Chemistry.Northeast Normal UniversityChangchun 130021China State Key Laboratory of Molecular Engineering of PolymersFudan UniversityShanghai 200433China Jilin Biomedical Polymers Engineering LaboratoryChangchun 130022China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2020年第31卷第5期

页      面：1129-1132页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 0703[理学-化学] 10[医学] 

基　　金：financially supported by National Key Research and Development Program of China(No.2016YFC1100701) the National Natural Science Foundation of China(Nos.51573184,51520105004 and 51833010) the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2017266)。 

主　　题：Polypeptides ROS-responsive Self-assembly Thioether Drug release 

摘      要：Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species(ROS)-responsive drug release.The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization(ROP)of 1,4-dithian-substituted L-glutamate N-carboxyanhydride(DTG-NCA)monomer using an amino-terminated poly(ethylene glycol)methyl ether(mPEG-NH2)as the macro molecular initiator.The resulta nt block copolyme r,mPEG-b-PDTG,could self-assemble into unifo rm micelles in aqueous medium owing to its amphiphilic structure.Then,the H2 O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering(DLS),FT-IR and turbidimetric assay.It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles.Furthermore,the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug.MTT assay also proved that mPEG-b-PDTG was non-toxic in B16 F10 and L929 cells.Therefore,such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.