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 

机构地区：[1]Key Laboratory of Functional Polymer Materials of Ministry of Education,Institute of Polymer Chemistry,College of Chemistry,Nankai University,Tianjin,300071,China [2]Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou Key Laboratory of Interdiscipline and Translational Medicine,Wenzhou,325001,China [3]Translational Medicine Laboratory,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China

出　　处：《Science China Chemistry》2023年第8期2354-2362,共9页中国科学（化学英文版）

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

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 carriers.However,efficient intracellular delivery of protein drugs remains a challenge because of the cell membrane barrier and endosome entrapment.Herein,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 delivery.PEG-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 proteins.Under a slightly acidic environment near cancer cells,the protonation of PAE(Im)backbone increases the positive charge density of the nanocomplex and promotes endocytosis.While 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 effect.Finally,protein is released into the cytoplasm.With the assistance of the nanocomplex,proteins with different sizes and isoelectric points are effectively delivered into cells.This work provides a stable,efficient and universal strategy for intracellular protein delivery.

关 键 词：PROTEIN zinc ions intracellular delivery COORDINATION POLYMER 

分 类 号：TQ460.4[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程]