Dynamic Protein Corona of Gold Nanoparticles with an Evolving Morphology

Much has been learned about the protein coronae and their biological implications within the context of nanomedicine and nanotoxicology. However, no data is available about the protein coronae associated with nanoparticles undergoing spontaneous surface-energy minimization, a common phenomenon during the synthesis and shelf life of nanomaterials. Accordingly, here we employed gold nanoparticles (AuNPs) possessing the three initial states of spiky, midspiky, and spherical shapes and determined their acquisition of human plasma protein coronae with label-free mass spectrometry. The AuNPs collected coronal proteins that were different in abundance, physicochemical parameters, and interactive biological network. The size and structure of the coronal proteins matched the morphology of the AuNPs, where small globular proteins and large fibrillar proteins were enriched on spiky AuNPs, while large proteins were abundant on spherical AuNPs. Furthermore, the AuNPs induced endothelial leakiness to different degrees, which was partially negated by their protein coronae as revealed by confocal fluorescence microscopy, in vitro and ex vivo transwell assays, and signaling pathway assays. This study has filled a knowledge void concerning the dynamic protein corona of nanoparticles possessing an evolving morphology and shed light on their implication for future nanomedicine harnessing the paracellular pathway.