# Terminal sialic acids in the nanoparticle corona modulate cellular uptake

## TL;DR

The study shows that sialic acids in the nanoparticle corona affect how nanoparticles are taken up by cells, which could help improve their therapeutic use.

## Contribution

The novel finding is that sialic acid content in the corona modulates nanoparticle interactions with glycan receptors and cellular uptake.

## Key findings

- Differences in sialic acid content alter NP-corona interactions with glycan receptors.
- Flow cytometry confirmed the impact of glycosylation on cellular uptake in relevant cell lines.
- Glycan composition of the corona influences nanoparticle stability and biological fate.

## Abstract

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.

Nanoparticles (NPs) hold promise for therapeutic applications, but their interactions with biological environments remain poorly understood. Here, the authors reveal that the glycosylation of the biomolecular corona, particularly sialic acid content, significantly influences NP interactions with cellular uptake processes, offering new insights into predicting NPs’ biological fate.