Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins

作     者：Sheng Liang Yang Liu Xin Jin Gan Liu Jing Wen Linlin Zhang Jie Li Xubo Yuan Irvin S.Y. Chen Wei Chen Hui Wang Linqi Shi Xinyuan Zhu Yunfeng Lu 

作者机构：Department of Nuclear Medicine Xinhua HospitalAffiliated to Shanghai Jiao Tong University Shanghai Jiao Tong University Shanghai 200092 China Department of Chemical and Biomolecular Engineering University of California Los Angeles CA 90095 USA Department of Microbiology Immunology and Molecular Genetics University of California Los Angeles CA 90095 USA Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) Key Laboratory of Functional Polymer Materials of Ministry of Education and State Key Laboratory of Medicinal Chemical Biology Institute of Polymer Chemistry Nankai University Tianjin 30007 I China School of Chemistry and Chemical Engineering ShanghaiJiao Tong University Shanghai 200240 China School of Materials Science and Engineering Key Laboratory of Composite and Functional Materials Tianjin University Tianjin 300072 China Beiiina Institute ofBiatechnoloav. Beiiina 100071. China 

出 版 物：《Nano Research》 (纳米研究（英文版）)

年 卷 期：2016年第9卷第4期

页      面：1022-1031页

核心收录：

学科分类：071010[理学-生物化学与分子生物学] 0808[工学-电气工程] 081704[工学-应用化学] 0809[工学-电子科学与技术（可授工学、理学学位）] 07[理学] 08[工学] 09[农学] 090603[农学-临床兽医学] 0710[理学-生物学] 0817[工学-化学工程与技术] 0906[农学-兽医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0702[理学-物理学] 

基　　金：This work is supported by the National Natural Science Foundation of China (NSFC  Nos. 91127045  51390483  51473319  51303025  81401439 and 51343007)  YG2012MS38 and China Postdoctoral Science Foundation (No. 2014M551399) 

主　　题：protein nanocapsule,protein delivery,protein therapy long-circulation,stealth therapeutic 

摘      要：Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.