Adsorption at cell surface and cellular uptake of silica nanoparticles with different surface chemical functionalizations: impact on cytotoxicity

Silica nanoparticles are particularly interesting for medical applications because of the high inertness and chemical stability of silica material. However, at the nanoscale their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological toxicity of silica nanoparticles depending on their surface chemical functionalization. To that purpose, three kinds of 50 nm fluorescent silica-based nanoparticles were synthesized: (1) sterically stabilized silica nanoparticles coated with neutral polyethylene glycol molecules, (2) positively charged silica nanoparticles coated with amine groups, and (3) negatively charged silica nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 h with each kind of nanoparticles. Their cellular uptake and adsorption at the cell membrane were assessed by a fluorimetric assay, and cellular responses were evaluated in terms of cytotoxicity, pro-inflammatory factor production, and oxidative stress. Results showed that the highly positively charged nanoparticle were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticle types. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and biological toxicity.