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Nano Research 2016, 9(4): 1022-1031 https://doi.org/10.1007/s12274-016-0991-3
Research Article | Issue | Published: 01 February 2016

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

Show Author's Information Sheng Liang1,§,  Yang Liu2,4,§,  Xin Jin5,§,  Gan Liu4,  Jing Wen3,  Linlin Zhang1,  Jie Li2,  Xubo Yuan6,  Irvin S. Y. Chen3,  Wei Chen7,  Hui Wang1( ),  Linqi Shi4( ),  Xinyuan Zhu5( ),  Yunfeng Lu2( )
Department of Nuclear MedicineXinhua Hospital Affiliated to Shanghai Jiao Tong UniversityShanghai Jiao Tong UniversityShanghai200092China
Department of Chemical and Biomolecular EngineeringUniversity of California, Los AngelesCA90095USA
Department of Microbiology, Immunology, and Molecular GeneticsUniversity of California, Los AngelesCA90095USA
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 BiologyInstitute of Polymer ChemistryNankai UniversityTianjin300071China
School of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai200240China
School of Materials Science and EngineeringKey Laboratory of Composite and Functional MaterialsTianjin UniversityTianjin300072China
Beijing Institute of BiotechnologyBeijing100071China

§ These authors contributed equally to this work.

Keywords:
protein therapy, long-circulation, protein nanocapsule, protein delivery, stealth therapeutic
Cite this article:
Liang S, Liu Y, Jin X, et al. Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins. Nano Research, 2016, 9(4): 1022-1031. https://doi.org/10.1007/s12274-016-0991-3
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Abstract Full text Electronic supplementary material About this article

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.


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Electronic supplementary material
About this article

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

Show Author's information Sheng Liang1,§, Yang Liu2,4,§, Xin Jin5,§, Gan Liu4, Jing Wen3, Linlin Zhang1, Jie Li2, Xubo Yuan6, Irvin S. Y. Chen3, Wei Chen7, Hui Wang1( ), Linqi Shi4( ), Xinyuan Zhu5( ), Yunfeng Lu2( )
Department of Nuclear MedicineXinhua Hospital Affiliated to Shanghai Jiao Tong UniversityShanghai Jiao Tong UniversityShanghai200092China
Department of Chemical and Biomolecular EngineeringUniversity of California, Los AngelesCA90095USA
Department of Microbiology, Immunology, and Molecular GeneticsUniversity of California, Los AngelesCA90095USA
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 BiologyInstitute of Polymer ChemistryNankai UniversityTianjin300071China
School of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai200240China
School of Materials Science and EngineeringKey Laboratory of Composite and Functional MaterialsTianjin UniversityTianjin300072China
Beijing Institute of BiotechnologyBeijing100071China

§ These authors contributed equally to this work.

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.

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

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Publication history
Copyright
Acknowledgements

Publication history

Received: 10 October 2015
Revised: 10 December 2015
Accepted: 27 December 2015
Published: 01 February 2016
Issue date: April 2016

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgements

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).

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