An investigation of protein affinities and interactions that occur at the interface between a new biodegradable nanohydrogel and albumin is being carried out in this work. Following intravenous injection, nanoparticles are covered by a 'protein corona' (PC), which influences their blood circulation time, biodistribution, cellular uptake, and intracellular localization. Exact understanding of the PC's qualitative and quantitative characteristics has a significant impact on the future of nanoparticles and their safe and efficient applications1. In this work, we report the formulation of novel nanohydrogel based on a hydrophilic core of thiolated hyaluronic acid and a hydrophobic shell composed of a synthetic copolymer: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer. Nanohydrogels were fully characterized in terms of particles size, distribution, and particle shape. The main objective of this study was to investigate the interactions between nanohydrogel and protein corona evaluating how the PC could affect the nanohydrogel internalization in macrophages.