Effect of Albumin Corona Conformation on In Vitro and In Vivo Profiles of Intravenously Administered Nanoparticles

Under physiological conditions, nanoparticles (NPs) inevitably interact with proteins, resulting in extensive protein adsorption and the formation of a protein corona. Recent studies have shown that the different surface properties of NPs lead to varying degrees of conformational changes of adsorbed proteins. However, the impact of corona protein conformation on the in vitro and in vivo profiles of NPs remain largely unexplored. Herein, d-α-tocopherol polyethylene glycol 1000 succinate-based NPs with natural human serum albumin (HSAN) corona or thermally denatured HSA (HSAD) corona were synthesized following a previously established method. We then conducted a systematic study of the protein conformation as well as adsorption behaviors. Additionally, the impact of protein corona conformation on the NPs profiles in vitro and in vivo were elucidated to gain insight into its biological behaviors as a targeted delivery system for renal tubule diseases. Overall, NPs modified by HSAN corona showed improved serum stability, greater cell uptake efficiency, better renal tubular targetability, and therapeutic efficacy on acute kidney injury in rats than NPs modified by HSAD corona. Hence, the conformation of protein adsorbed on the surface of NPs may impact the in vitro and in vivo profiles of NPs.