Stereoselective coronas regulate the fate of chiral gold nanoparticles in vivo

It is unknown how the identity provided by protein coronas on the surface of chiral nanoparticles determines their blood circulation, distribution, and clearance fates of the nanoparticles in vivo. Here, we attempt to investigate how the mirrored surface of gold nanoparticles with distinct chirality reshapes the coronal composition that mediates their subsequent clearance from blood and biodistribution. We found that chiral gold nanoparticles exhibited surface chirality-specific recognition for the coronal components, including the lipoproteins, complement components, and acute phase proteins, ultimately resulting in distinct cell uptake and tissue accumulation in vivo. We observed that these stereoselective behaviors were correlated to subgroups of the corona composition that could bind to low-density lipoprotein receptors. Therefore, this study reveals how chirality-specific protein compositions selectively recognize and interact with cell receptors for chirality-mediated tissue accumulation. This study will deepen our understanding of how chiral nanoparticles/nanomedicine/nanocarriers interact with biological systems to guide the efficient fabrication of target nanomedicines.