Biological Behavior Regulation of Gold Nanoparticles via the Protein Corona

Abstract One of the difficulties in the translation of gold nanoparticles (GNPs) into clinical practice is the formation of the protein corona (PC) that causes the discrepancy between the in vitro and in vivo performance of GNPs. The PC formed on the surface of GNPs gives them a biological identity instead of an initial synthetic one. In most instances, this biological identity increases the particle size, leads to more clearance by the reticuloendothelial system, and causes less uptake by target cells. However, the performance of GNPs can still be improved by rewriting their original surface chemistry via the PC. This review specifically focuses on discussing the main influence factors, including the biological environment and physicochemical properties of GNPs, which affect the production and status of the PC. The status of the PC such as the amount, thickness, and composition subsequently influence the biological behavior of GNPs, especially their cellular uptake, cytotoxicity, biodistribution, and tumor targeting. Further understanding and revealing the impacts of the PC on the biological behavior of GNPs can be a promising and important strategy to regulate and improve the performance of GNP‐based biosystems in the future.