Protein@PP-Zn nanocomplex assembled by coordination of zinc ions used for intracellular protein delivery

作     者：Liyun Cui Sainan Liu Fan Wu Hua Chen Yuanfeng Li Linqi Shi Yong Liu Rujiang Ma 

作者机构：Key Laboratory of Functional Polymer Materials of Ministry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071China Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou Key Laboratory of Interdiscipline and Translational MedicineWenzhou325001China Translational Medicine Laboratorythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325035China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2023年第66卷第8期

页      面：2354-2362页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 0702[理学-物理学] 

基　　金：supported by the National Natural Science Foundation of China(51773099 52203184 22275043 51933006) 

主　　题：protein zinc ions intracellular delivery coordination polymer 

摘      要：In recent years,intracellular delivery of protein drugs has attracted great attention,and polymer-based systems have been extensively exploited to develop efficient and safe ***,efficient intracellular delivery of protein drugs remains a challenge because of the cell membrane barrier and endosome ***,we report a protein@PP-Zn nanocomplex,which consists of an imidazole-containing block polymer poly(ethylene glycol)-block-poly(β-amino ester)(PEG-b-PAE(Im),PP),zinc ions,and protein drugs,for efficient intracellular protein ***-b-PAE(Im)could conjugate proteins via the bridging effect of zinc ions which simultaneously coordinate with imidazole groups on polymer and electron donor groups,such as imidazole and primary amine groups,on protein to improve the loading stability of *** a slightly acidic environment near cancer cells,the protonation of PAE(Im)backbone increases the positive charge density of the nanocomplex and promotes *** under a more acidic environment in endosomes,further protonation of imidazole groups leads to the disintegration of the nanocomplex and the breakdown of endosomes because of the proton sponge ***,protein is released into the *** the assistance of the nanocomplex,proteins with different sizes and isoelectric points are effectively delivered into *** work provides a stable,efficient and universal strategy for intracellular protein delivery.