Impact of the Glycan Component of the Biomolecular Corona Formed Around Nanoparticles

Abstract

Advances in engineering functional structures at the nanoscale have led to the generation of a wide range of nanoparticles (NPs) that have promising therapeutic applications as drug delivery tools. However, when NPs get in contact with a complex biological milieu, they strongly interact with the available biomolecules, mostly glycoproteins, gaining a new layer defined as the “corona”. Recent findings have shown that the glycan component of the corona can affect NPs stability and it is unclear whether it can modulate biological responses through the glycan-binding receptors present in the body. This study developed a new platform to obtain a quantitative and qualitative characterisation of the corona glycosylation and tested its capability to modulate the NP uptake after being exposed to different cell lines. To address this problem, fluorescently labelled 100nm silica NPs were coated with two different biomolecular coronas derived from human plasma, reflective in a diverse glycosylation pattern. The two biomolecular layers of the NPs were characterized in their protein and glycosylated components using a platform recently established in our group with the support of an industrial partner. As the glycans are biologically active molecules, the ones forming the corona were tested to evaluate if they could directly control the NP-corona complexes’ biological fate. Finally, the uptake of the NP-biomolecular coronas in macrophage and hepatocyte cell models was tested, with a focus on the influence of N-glycans and their terminal monosaccharide sialic acid. This research showed that specific glycosylation of the corona could influence the recognition of the nanomaterials, and that differences in the presence of the sialic acid could change the NP-biomolecular corona interaction processes. Overall, these findings may clarify specific nanomaterial behaviours, and give new parameters to predict or functionalise drug carriers for future therapies.</p