Understanding the Biomolecular Coronas of High-Density Lipoproteins on PEGylated Au Nanoparticles: Implication for Lipid Corona Formation in the Blood

To understand the formation of lipid coronas around engineered nanoparticles (NPs) in the blood, which may be produced by lipoproteins, i.e., the main lipid sources in the blood, we investigated the biomolecular compositions of the hard coronas around PEGylated Au NPs produced by high-density lipoproteins (HDLs). In this study, we used mass spectrometric profiling to evaluate 19 representative HDL lipids, the relative abundances of which were found to be altered in the hard coronas compared with that in HDLs. In addition, the composition of phospholipids (PLs) in the coronas did not show any dependence on NP size, despite the evident size dependence in adsorbed HDL quantity. These suggest that during the adsorption of whole HDL complexes on the NPs, which prefer less curved NP surfaces, HDLs undergo disintegration while their constituents coat the PEGylated surfaces of NPs. On the other hand, neutral lipids, which are water-insoluble lipid cargo, exhibited compositions that irregularly varied among experimental batches. Their participation in the corona formation is attributed to hydrophobicity rather than explicit interaction with the PEGylated surfaces. Among them, free cholesterol (Chol) was remarkably enriched in the coronas, which was 20–100 times larger than that of other lipids and apolipoprotein A1. Considering that Chol is an important structural component in cellular membranes, its noticeable enrichment may suggest its possible involvement in the structures of lipid coronas through interactions with neighboring PLs, of which excess accumulation may play a critical role in the pathogenesis of multiple diseases. The elucidated features of HDL coronas were found to be reflected in the lipid coronas produced in the human serum as well. This understanding of biomolecular coronas produced by HDL complexes would provide further insights to investigate their biological impacts beyond protein coronas for designing future nanomedicines.