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

nano Research 2016年第8期9卷 2424-2432页

作者： Linlin Zhang Yang Liu Gan Liu Duo Xu Sheng Liang Xinyuan Zhu Yunfeng Lu Hui Wang Department of Nuclear Medicine Xinhua Hospital Affiliated to Shanghai Jiao Tong University Shanghai Jiao Tong University Shanghai 200092 China Department of Chemical and Biomolecular Engineering University of California Los Angeles California 90095 USA 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 School of Chemistry and Chemical Engineering Shanghai Jiao Tong University Shanghai 200240 China Key Laboratory of Functional Polymer Materials Ministry of Education Institute of Polymer Chemistry Nankai University Tianjin 300071 China

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 drculation. 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.

关键词： phosphorylcholine-basedpolymer nano-encapsulation function protein delivery protein therapy long-circulation

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