The goal of this study was to investigate the impact of nanoparticle surface chemistry on interactions with media containing fetal bovine serum concentrations used in routine cell culture conditions and the resulting physical and chemical properties of the nanoparticle. Previous work has shown the in situ agglomeration of polymeric nano-and micro-particles following administration to pre-clinical species, an aspect that has not been investigated during in vitro assessment of nanoparticle interactions with biological media . Specifically, we use polystyrene latex nanoparticles as a model nanoparticle system (due to minimal polymer hydrolysis effects) and employ sample media with the same protein content and composition as those studied for in vitro cellular experiments of nanoparticle cellular uptake and biocompatibility evaluation.