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

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Abstract

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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Authors and Affiliations

  1. Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai, 200092, China

    Linlin Zhang & Hui Wang

  2. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California, 90095, USA

    Yang Liu, Duo Xu & Yunfeng Lu

  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

    Gan Liu & Sheng Liang

  4. School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xinyuan Zhu

  5. Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin, 300071, China

    Yang Liu

Authors
  1. Linlin Zhang
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  2. Yang Liu
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  3. Gan Liu
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  4. Duo Xu
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  5. Sheng Liang
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  6. Xinyuan Zhu
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  7. Yunfeng Lu
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  8. Hui Wang
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Correspondence to Xinyuan Zhu, Yunfeng Lu or Hui Wang.

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These authors contributed equally to this work.

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Zhang, L., Liu, Y., Liu, G. et al. Prolonging the plasma circulation of proteins by nano-encapsulation with phosphorylcholine-based polymer. Nano Res. 9, 2424–2432 (2016). https://doi.org/10.1007/s12274-016-1128-4

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

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