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Nano Research

Article Title

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

Authors

Sheng Liang, Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China
Yang Liu, Department of Chemical and Biomolecular Engineering, 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 300071, China
Xin Jin, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Gan Liu, 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 300071, China
Jing Wen, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Linlin Zhang, Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China
Jie Li, Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA
Xubo Yuan, School of Materials Science and Engineering, Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China
Irvin S. Y. Chen, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Wei Chen, Beijing Institute of Biotechnology, Beijing 100071, China
Hui Wang, Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China
Linqi Shi, 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 300071, China
Xinyuan Zhu, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Yunfeng Lu, Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA

Keywords

protein nanocapsule, protein delivery, protein therapy, long-circulation, stealth therapeutic

Abstract

Protein therapy, 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 nanoparticles 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.

Graphical Abstract

Publisher

Tsinghua University Press

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