The adsorption of proteins on nanoparticles (NPs) largely decides the fate and bioeffects of NPs in vivo. However, bio-fluids are too complicated to directly study in them to reveal related mechanisms, and current studies on model systems often ignore some important biological factors, such as metal ions. Herein, we evaluate the effect of Ca2+ at physiological concentrations on the protein adsorption on negatively-charged silica NP (SNP50). It is found that Ca2+, as well as Mg2+ and several transition metal ions, significantly enhances the adsorption of negatively-charged proteins on SNP50. Moreover, the Ca2+-induced enhancement of protein adsorption leads to the reduced uptake of SNP50 by HeLa cells. A double-chelating mechanism is proposed for the enhanced adsorption of negatively-charged proteins by multivalent metal ions that can form 6 (or more) coordinate bonds, where the metal ions are chelated by both the surface groups of NPs and the surface residues of the adsorbed proteins. This mechanism is consistent with all experimental evidences from metal ions-induced changes of physicochemical properties of NPs to protein adsorption isotherms, and is validated with several model proteins as well as complicated serum. The findings highlight the importance of investigating the influences of physiological factors on the interaction between proteins and NPs.
Keywords: Chelation; Metal ions; Protein adsorption; Protein corona; Silica nanoparticle.
Copyright © 2023 Elsevier Inc. All rights reserved.