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.
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）.
