Nanoparticle interactions with organic methods are intricate processes influenced by numerous components, amongst which the formation of a protein corona performs a pivotal position. This analysis investigates a novel side of nano protein corona-cell interactions, specializing in the affect of the protein corona on the restoration of disrupted tight junctions in endothelial cells. We exhibit that nanoparticle form might not play a big position in protein corona composition however the protein corona on the star nanoparticles induces the aggregates of ZO-1, which is sort of vital for the boundaries’ integrity. Our analysis emphasizes the APOA1 pre-coating on the nanoparticles scale back a ZO-1 expression of endothelial cells providing a promising technique for overcoming the bio boundaries. These findings contribute to our understanding of the interaction between nanoparticles, protein corona, and endothelial cell junctions, providing insights for creating progressive therapeutic approaches concentrating on blood-brain barrier integrity. Our research holds promise for the way forward for nanomedicine. Understanding the interaction between nanoparticles, protein corona, and tight junction dynamics holds promise for advancing our data of the nano drug supply methods and creating methods to mitigate potential antagonistic results.