The “Sweet” Side of the Protein Corona: Effects of Glycosylation on Nanoparticle–Cell Interactions

TLDR

The protein corona, formed from glycosylated proteins in biological fluids, is known to modulate nanoparticle properties and biological interactions, yet the role of glycans has largely been overlooked. This study investigates how glycosylation of the protein corona affects nanoparticle colloidal stability and cell interactions. Removing glycans increases nanoparticle adhesion and uptake by cells, triggering a pro‑inflammatory response in macrophages, demonstrating that post‑translational modifications of corona proteins can markedly alter nanoparticle–cell interactions.

Abstract

The significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions has been widely acknowledged. The protein corona is derived from proteins in biological fluids, many of which are glycosylated. To date, the glycans on the proteins have been largely overlooked in studies of nanoparticle–cell interactions. In this study, we demonstrate that glycosylation of the protein corona plays an important role in maintaining the colloidal stability of nanoparticles and influences nanoparticle–cell interactions. The removal of glycans from the protein corona enhances cell membrane adhesion and cell uptake of nanoparticles in comparison with the fully glycosylated form, resulting in the generation of a pro-inflammatory milieu by macrophages. This study highlights that the post-translational modification of proteins can significantly impact nanoparticle–cell interactions by modulating the protein corona properties.