Biopolymer nanoparticle surface chemistry dictates the nature and extent of protein hard corona

Abstract

Biopolymer nanoparticles functionalized with targeting ligands serve as carriers for a wide range of therapeutic payloads to desired sites of the body. Upon introduction into the blood stream, the nanoparticles tend to bind with the plasma proteins in its immediate vicinity, forming a protein corona. In this work, we have investigated the effects of differently functionalized PLGA nanoparticles on the formation of protein corona. It was observed that nanoparticles of uniform size range adsorbed protein in varying amounts and the final hard corona differed structurally with respect to nanoparticle surface functionalization. A combination of fluorescence spectroscopy and FTIR studies revealed that the association of plasma proteins with PLGA nanoparticles during corona formation was intricately guided by the nanoparticle surface chemistry. Densitometric analysis through one dimensional gel electrophoresis further showed that the plasma proteins present in the hard corona were different for each case of surface functionalization. The aggregation of plasma protein during corona formation as studied through Thioflavin T fluorescence and circular dichorism spectroscopy was also found to significantly differ with each nanoparticle type. It is evident that surface chemistry of biopolymeric nanoparticles defines the final corona form in the physiological environment, and this study on detailed understanding of nanoparticle-protein corona would help to develop nanomedicines for clinical applications.