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

作　　者：Linlin Zhang Yang Liu Gan Liu Duo Xu Sheng Liang Xinyuan Zhu Yunfeng Lu Hui Wang 

机构地区：[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

出　　处：《Nano Research》2016年第8期2424-2432,共9页纳米研究（英文版）

基　　金：This work is supported by the National Natural Science Foundation of China （NSFC, Nos. 51343007, 81271612 and 81401439）, Shanghai Pujiang Program （No. 13PJD022）, and Shanghai Health Bureau Fund （No. 20124016）.

摘　　要：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.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 

分 类 号：O[理学]