The formation of protein corona on the nanoparticle surface.Immediately after the in vivo administration of nanoparticles, low-affinity proteins in high concentrations are absorbed on their surface;these are replaced by proteins with a higher affinity after a long exposure time (the Vroman effect). Low-affinity proteins form a so-called “soft” corona layer, while the high-affinity proteins form a strongly bound layer of “hard” corona. Hard corona proteins are located closest to the nanoparticle surface, which makes them more sensitive to thermodynamic changes (irreversible) depending on the functionality, hydrophobicity, or hydrophilicity of the nanoparticle and the nature and temperature of the biological fluid. The soft corona is not directly connected to the surface of the nanoparticle, and only weak interaction forces are present.