Research Article

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2016, 9(8): 2424–2432

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https://doi.org/10.1007/s12274-016-1128-4

Prolonging the plasma circulation of proteins by nano-encapsulation with phosphorylcholine-based polymer

Linlin Zhang1,§,Yang Liu2,5,§, Gan Liu3,§, Duo Xu2, Sheng Liang3, Xinyuan Zhu4 (*), Yunfeng Lu2 (*), and Hui Wang1 (*)

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1 Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China
2 Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA
3 The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and Biomedicine and Division of Life and Health Sciences, Tsinghua University, Shenzhen 518055, China
4 School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
5 Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China
§ These authors contributed equally to this work.

Keywords: phosphorylcholine-basedpolymer,nano-encapsulation,function protein delivery,protein therapy,long-circulation
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  • Abstract
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Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a two-step encapsulation process exhibited significantly prolonged plasma half-life. Furthermore, by constructing nanocapsules with similar sizes but different surface charges and chemistry, we demonstrated a generic strategy for prolonging the plasma half-life of therapeutic proteins. In an in vitro experiment, four types of bovine serum albumin (BSA) nanocapsules were incubated with fetal bovine serum (FBS) in phosphate buffer saline (PBS); the cell uptake by HeLa cells was monitored to systematically evaluate the characteristics of the surface chemistry during circulation. Single positron emission tomography–computed tomography (SPECT) was employed to allow real-time observation of the BSA nanoparticle distribution in vivo, as well as quantification of the plasma concentration after intravenous administration. This study offers a practical method for translating a broad range of proteins for clinical use.
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Prolonging the plasma circulation of proteins by nano-encapsulation with phosphorylcholine-based polymer. Nano Res. 2016, 9(8): 2424–2432 https://doi.org/10.1007/s12274-016-1128-4

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