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 

机构地区：[1]Department of Nuclear Medicine, Xinhua HospitalAffiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China [2]Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA [3]Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA [4]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 [5]School of Chemistry and Chemical Engineering, ShanghaiJiao Tong University, Shanghai 200240, China [6]School of Materials Science and Engineering, Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China [7]Beiiina Institute ofBiatechnoloav. Beiiina 100071. China

出　　处：《Nano Research》2016年第4期1022-1031,共10页纳米研究（英文版）

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）.

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.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.

关 键 词：protein nanocapsule protein delivery protein therapy long-circulation stealth therapeutic 

分 类 号：S858.315.3[农业科学—临床兽医学] Q51[农业科学—兽医学]