Nanoparticle interactions with biological systems are intricate processes influenced by various factors, among which the formation of protein corona plays a pivotal role. This research investigates a novel aspect of nanoprotein corona–cell interactions, focusing on the impact of the protein corona on the recovery of disrupted tight junctions in endothelial cells. We demonstrate that the protein corona formed on the surface of star-shaped nanoparticles induces the aggregates of ZO-1, which is quite important for the barriers’ integrity. Our research emphasizes that the APOA1 pre-coating on the nanoparticles reduces the ZO-1 expression of endothelial cells offering a promising strategy for overcoming the bio barriers. These findings contribute to our understanding of the interplay between nanoparticles, protein corona, and endothelial cell junctions, offering insights for developing innovative therapeutic approaches targeting the blood–brain barrier integrity. Our study holds promise for the future of nanomedicine, nano drug delivery systems and development of strategies to mitigate potential adverse effects.
