Variations in metabolite profiles of serum coronas produced around PEGylated liposomal drugs by surface property.

Understanding biomolecular coronas that spontaneously occur around nanocarriers (NCs) in biological fluids is critical to nanomedicine as the coronas influence the behaviors of NCs in biological systems. In contrast to extensive investigations of protein coronas over the past decades, understanding of the coronas of biomolecules beyond proteins, e.g., metabolites, has been rather limited despite such biochemicals being ubiquitously involved in the coronas, which may influence the bio-nano interactions and thus exert certain biological impacts. In this study, serum biomolecular coronas, in particular the coronas of metabolites including lipids, around PEGylated doxorubicin-loaded liposomes with different surface property were investigated. The surface properties of liposomal drugs varied in terms of surface charge and PEGylation density by employing different ionic lipids such as DOTAP and DOPS and different concentrations of PEGylation lipids in liposome formulation. Using the liposomal drugs, the influence of the surface property on the serum metabolite profiles in the coronas was traced for target molecules of 220 lipids and 88 hydrophilic metabolites. From the results, it was found that metabolites rather than proteins mainly constitute the serum coronas on the liposomal drugs. Most of the serum metabolites were found to be retained in the coronas but with altered abundances. Depending on their class, lipids exhibited a different dependence on the surface property. However, overall, lipids appeared to favor corona formation on more negatively charged and PEGylated surfaces. Hydrophilic metabolites also exhibited a similar propensity for corona formation. This study on the surface dependence of metabolite corona formation provides a fundamental contribution toward attaining a comprehensive understanding of biomolecular coronas, which will be critical to the development of efficient nanomedicine.

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

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.