Surface properties modulate protein corona formation and determine cellular uptake and cytotoxicity of silver nanoparticles

The lack of the basic understanding of how NPs interact with the biological environment has severely limited their delivery efficiency to target tissue and clinical translation. Here, we show the effective regulation of the surface properties of NPs, cellular uptake and cytotoxicity. Surface properties of NPs are tuned through the controlled replacement of native ligands, which favor protein adsorption, with ligands able to increase protein adsorption resistance. The extent and composition of the protein layer adsorbed on NPs are strongly correlated to the degree of ligands replaced on their surface and, while BSA is the most abundant protein detected, ApoE is the one whose amount is most affected by surface properties. Increasing the protein resistance, cellular uptake and cytotoxicity in mouse embryonic fibroblasts of NPs are drastically reduced, but surface coating has not effects on the process by which NPs mainly induce cell death.