Investigating the impact of shear flow on nanoparticle-protein interactions

Most nanoparticle-based therapies are intended for intravenous administration, exposing them to associated hemodynamic parameters and the presence of cells and biomacromolecules post-administration. While most efforts in nanomedicine development focus on formulation stability, the range of biologically-relevant approaches probing nanoparticle stability in biological media remains limited in scope. In the present study, we examine the role of surface chemistry in nanoparticle-protein interactions using three polystyrene latex nanoparticle chemistries. These nanoparticles were treated in media mimicking cell culture conditions, and the impact of static co-incubations versus flow on nanoparticle parameters was compared. Following treatment with protein-containing media, we performed an analysis of nanoparticle parameters using either the centrifugation-wash step or in-situ analyses to compare the effects of isolation protocols on nanoparticle physicochemical parameters. Overall, our findings show that flow and sample recovery methods significantly impacted the concentration and composition of surface-adsorbed proteins. Amine-modified latex nanoparticles showed the most pronounced susceptibility to flow and nanoparticle isolation techniques. The implications of this work lie in the development of more biologically-relevant and harmonized approaches in measuring the nanoparticle protein corona, since sample preparation techniques and analytical approaches used, may impact the translational scope and relevance of assays used to measure nanoparticle interactions with biological media.