Here, we assessed the impact of nanoparticle surface chemistry on changes in particle size and size distribution in response to treatment with media containing FBS. We selected polystyrene latex nanoparticles as a model system due to their chemical stability over the duration and range of conditions examined in this study, to exclude effects resulting from polymer degradation. The protein incubation conditions selected for this work were based on the typical protein serum concentrations used in in vitro cell culture experiments, which are normally used for the early in vitro evaluation of nanoparticle interactions with biological media.