The optimal design of nanoparticles (NPs) for biomedical applications [1], requires a critical and thorough characterization of their physicochemical properties in physiological fluids 2, 3, 4. Physiological fluids, such as blood, saliva, gastrointestinal mucus, and lymph fluid, are rich in ions, small molecules (vitamins, hormones, and sugars), and biomacromolecules (proteins, glycoproteins, and lipids) [3]. These components readily interact with NPs 3, 5, which may change the physicochemical interface at the fluid-particle surface [6]. Such interactions may result in a biomolecular corona covering the particle surface 7, 8, 9, 10, 11, 12, 13, 14••, in removing stabilizing polymeric ligands [15], and in compressing the electric double layer (EDL) [16]. These affect not only the integrity and colloidal stability of the NPs [17], that is, whether or not agglomeration (or aggregation), dissolution, removal, and exchange of molecules attached to their surface happens 15, 18, 19, but also the circulation time in the bloodstream, organ accumulation, and interactions with specific cells [20]. Internalization of NPs by cells may happen by various routes depending on dimensions and surface properties of the NPs [1], and understanding the relationships between physicochemical properties and the cellular outcome is of utmost importance 21, 22.