Size Dependence Unveiling the Adsorption Interaction of High-Density Lipoprotein Particles with PEGylated Gold Nanoparticles in Biomolecular Corona Formation

Abstract

Apolipoproteins have been often found to be highly enriched in the serum protein coronas produced on various engineered nanoparticles (NPs), which is also known to greatly influence the behaviors of protein corona NPs in the biological systems. As most of the apolipoproteins in blood are associated with lipoproteins, it suggests the active involvement of lipoproteins in the formation of biomolecular coronas on NPs. However, the interactions of lipoprotein complexes with NPs in the corona formation have been rarely understood. In this study, to obtain insights into the interactions, the formation of biomolecular coronas of high-density lipoproteins (HDLs) on the PEGylated gold NPs (PEG-AuNPs) of various sizes (20−150 nm dia.) was investigated as a model system. The results of this study revealed a noticeable size dependence, which is a drastic increase in the affinity of HDL for larger NPs and thus less-curved NP surfaces. For example, only a few HDLs per NP, which correspond to 5% surface coverage, were found to constitute the hard coronas of HDLs on 20 nm PEG-AuNPs, whereas 73% surface coverage was assessed for larger 150 nm PEG-AuNPs. However, the relative affinities of HDL and apolipoprotein A-1 (APOA1) examined in competition with human serum albumin exhibited the opposite size dependences, which suggests that the adsorption of HDLs is not driven by the constituent protein, APOA1. In fact, the total strength of non-covalent intermolecular interactions between a HDL particle and a NP relies on the physical contact between the two particles, which thus depends on the varying curvatures of spherical NPs in this case. Therefore, it was concluded that it is whole HDL complex that interacts with the spherical PEG-AuNPs in the initial stage of adsorption toward biomolecular coronas, which is unveiled by the distinct size dependence observed in this study.

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

“…), respectively, as well as one AuNRs (an aspect ratio of 3.4). We employed AuNPs of different sizes to examine the possible effects of NP size on the biomolecular composition of HDL coronas …”

“…For the absorption experiments, a UV–vis–NIR spectrophotometer (V-770, JASCO Co., Tokyo, Japan) was employed. From the measured ODs, the number densities of 20 and 150 nm spherical AuNPs were evaluated using the literature values of 7.0 × 10 11 and 1.7 × 10 9 /mL at OD = 1, respectively …”

“…The protein quantification was performed using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) as per the previously reported method. Detailed experimental methods can be found in the previous paper …”

“…, lipid bilayers, occurs in contact with NPs, which results in the lipid coronas around the NPs. , In a recent study, the affinity of HDL for corona formation has been found to clearly depend on the sizes of PEGylated AuNPs (PEG-AuNPs). This led to the conclusion that whole HDL complexes interact with PEG-AuNPs in the initial adsorption stage rather than being mediated by APOA1, resulting in the disintegration of HDLs on the NPs …”

“…Because a hard corona represents the layer of biomolecules that directly interact with NP surfaces, this study would deepen our understanding of the formation of coronas of biogenic complexes on the PEGylated surfaces of NPs. In this study, three differently sized AuNPs were utilized for examining possible size dependence . PEGylation was performed for the NP surfaces as it is widely used in biomedical applications.…”