The nanoparticle protein corona plays a key role in the biological fate of nanoparticles following administration to biological systems. Regulatory bodies including the European Medicine Agency (EMA) recommend the characterisation of nanoparticle physicochemical properties and their interaction with biological media across different stages of the nanomedicine drug development life cycle including in vitro and pre-clinical in vivo studies during early development . The adsorption of proteins onto the particle surface leads to changes in the nanoparticle physicochemical parameters including size, ζ-potential, shape, surface chemistry, surface charge and colloidal stability. These parameters influence nanoparticlecellular interactions and changes in these parameters will subsequently alter the nanoparticle biological fate Our goal in this work was to assess the role of nanoparticle surface chemistry in the physical fate of nanoparticles exposed to protein containing media under conditions mimicking cell culture protein content. Here, we studied the role of nanoparticle physical parameters in the range of nanoparticle-protein interactions using polystyrene latex nanoparticles (unmodified, amine-, and carboxylate-modified) as model nanoparticles. It is well known that proteins adsorb onto nanoparticle surfaces to form a protein corona, however there is a current lack of understanding on how the corona formation impacts nanoparticle size and size distribution, and how this subsequently governs the physical and compositional role of the nanoparticle protein corona in dictating nanoparticle pharmacological activities . Conversely, there is also a lack of understanding of how the protein corona contributes to an altered biological fate in the context of changes occurring in nanoparticle physical parameters (i.e., size and charge) following exposure to protein containing media and subsequent protein corona formation. While the focus of many studies to-date has been on the quantitative compositional analysis of the protein corona, there has been a limited focus on the quantitative physical changes occurring in nanoparticle systems in response to protein treatment . As such there is a clear need to develop a novel bioanalytical pipeline for the reproducible measurement of nanoparticle parameters in response to exposure to biological media as a crucial step in the development and translation of novel drug delivery systems .