Terminal sialic acids in the nanoparticle corona modulate cellular uptake

Advances in engineering functional structures at the nanoscale have led to the generation of a wide range of nanoparticles (NPs) with promising therapeutic applications. However, when NPs come into contact with a biological environment, they strongly interact with the available biomolecules, such as glycoproteins. Their adsorption on the NP's surface forms the " biomolecular corona". Recent findings have shown that the glycosylation of the corona affects NPs' stability, and it is unclear whether it can engage with receptors present in the body. By dissecting the corona's glycan composition with enzymatic approaches, we demonstrate, through differential centrifugal sedimentation and quartz crystal microbalance, that differences in the monosaccharide sialic acid content change the NP-corona interactions with isolated glycan receptors. Furthermore, flow cytometry data confirmed this behaviour in relevant cell lines. Overall, these findings highlight the role of the biomolecular corona glycosylation in NP's interaction, suggesting advanced parameters to predict their biological fate.