Complete high‐density lipoproteins in nanoparticle corona

TLDR

Nanoparticles rapidly acquire a biomolecular corona that defines their biological identity, and while prior studies focused on proteins, evidence shows that lipids and lipoproteins—including apolipoproteins—also bind broadly to nanoparticles in physiological settings. Using size‑exclusion chromatography, NMR, and pull‑down assays, we demonstrate that copolymer nanoparticles bind cholesterol, triglycerides, and phospholipids from human plasma until saturation. The binding patterns mirror high‑density lipoprotein (HDL) composition, with HDL—mediated by apolipoprotein A‑I—binding copolymer nanoparticles more specifically than other lipoproteins, indicating that the nanoparticles acquire complete HDL complexes that could be recognized by biological systems and exploit HDL transport pathways.

Abstract

In a biological environment, nanoparticles immediately become covered by an evolving corona of biomolecules, which gives a biological identity to the nanoparticle and determines its biological impact and fate. Previous efforts at describing the corona have concerned only its protein content. Here, for the first time, we show, using size exclusion chromatography, NMR, and pull‐down experiments, that copolymer nanoparticles bind cholesterol, triglycerides and phospholipids from human plasma, and that the binding reaches saturation. The lipid and protein binding patterns correspond closely with the composition of high‐density lipoprotein (HDL). By using fractionated lipoproteins, we show that HDL binds to copolymer nanoparticles with much higher specificity than other lipoproteins, probably mediated by apolipoprotein A‐I. Together with the previously identified protein binding patterns in the corona, our results imply that copolymer nanoparticles bind complete HDL complexes, and may be recognized by living systems as HDL complexes, opening up these transport pathways to nanoparticles. Apolipoproteins have been identified as binding to many other nanoparticles, suggesting that lipid and lipoprotein binding is a general feature of nanoparticles under physiological conditions.