Protein deglycosylation can drastically affect the cellular uptake.

Targeted drug delivery mediated by nanocarriers is a major issue in modern-day medicine. Upon coming in contact with biological fluids (e.g. blood), nanocarriers are rapidly covered by biomolecules (proteins, lipids, etc.) which results in the formation of a surface layer, widely known as the biomolecular corona. The biomolecular corona subsequently confers a certain biological identity to the corona-covered nanocarriers which can be crucial during their subsequent interactions with cells or other biological entities. In contrast to the proteins of the corona, little is known about the impact of the non-protein constituents of the corona, such as sugars. Here, we investigate the role of protein glycosylation of the corona in cellular uptake. We show that deglycosylation of clusterin (CLU) and apolipoprotein AI (Apo AI) significantly changes (increases and decreases, respectively) the cellular uptake of nanocarriers covered with these proteins.