Investigating the Impact of Shear Flow on Nanoparticle-Protein Interactions

Abstract

Most nanoparticle-based therapies are intended forintravenous administration, exposing them to associated hemodynamic parametersand the presence of cells and biomacromolecules post-administration. While mostefforts in nanomedicine development focus on formulation stability, the rangeof biologically-relevant approaches probing nanoparticle stability inbiological media remain limited in scope. In the present study, we examine therole of surface chemistry in nanoparticle-protein interactions using threepolystyrene latex nanoparticle chemistries. These nanoparticles were treated inmedia mimicking cell culture conditions, and the impact of static co-incubationsversus flow on nanoparticle parameters were compared. Following treatment withprotein-containing media, we performed analysis of nanoparticle parameters usingeither the centrifugation-wash step or in-situ analyses to compare the effectsof isolation protocols on nanoparticle physicochemical parameters. Overall, ourfindings show that flow and sample recovery methods significantly impacted the concentrationand composition of surface-adsorbed proteins. Amine-modified latex nanoparticlesshowed the most pronounced susceptibility to flow and nanoparticle isolationtechniques. The implications of this work lie in the development of more biologically-relevantand harmonized approaches in measuring the nanoparticle protein corona, sincesample preparation techniques and analytical approaches used, may impact the translationalscope and relevance of assays used to measure nanoparticle interactions withbiological media.