Triglyceride-Rich Conditions Reshape the Protein Corona and Alter Nanobio Interactions

Exposure of nanoparticles (NPs) to biological fluids
inevitably
results in rapid surface coating by biomolecules, mainly proteins,
forming what is commonly termed the protein corona (PC). The PC confers
a transformed biological identity to NPs that governs their interaction
with physiological systems and influences the pharmacological profile.
However, the role of blood metabolites in regulating PC and subsequent
nanobio interaction remains undefined. In this study, we examine the
impact of elevated triglyceride (TG) levels, clinically termed hypertriglyceridemia,
on PC modulation and its related physiological response and pharmacokinetics.
We observe that the elevated TG levels differentially regulate PC
formation by promoting the adsorption affinity of specific proteins
to NPs. The TG-rich PC induces a robust immune response in macrophages
by stimulating the release of pro-inflammatory cytokines compared
to normal-PC. In vivo experiments reveal that relative
to normal mice, NPs in hypertriglyceridemic (HTG) mice show more accumulation
and sequestration in the liver and spleen. Furthermore, PC formed
in HTG mouse serum shows higher uptake in macrophages and hepatocytes
than PC formed in normal mouse serum. Finally, the proteomic analysis
reveals distinct disparities in protein adsorption patterns: Lipoproteins
are more dominant in HTG-PC, whereas immunoglobulins and complement
proteins are more prevalent with normal-PC. Overall, this work offers
important insights into the predictive role of disease-related metabolites
on the modulating PC and nanobio interaction, aiding in the rational
design of nanomedicine.