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

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.