Uptake and cytotoxicity of silica nanoparticles with different surface functionalizations
Résumé
Silica nanoparticles are particularly interesting for medical applications because of their inertness and chemical stability. However, their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological effects of silica nanoparticles depending on their physico-chemical features. We especially focused on the impact of surface functionalization on biological toxicity. For this purpose, three kinds of stabilized fluorescent (FITC) silica nanoparticles were used: 1) sterically stabilized nanoparticles coated with neutral Polyethylene Glycol (PEG) molecules, 2) positively charged nanoparticles coated with amine groups and 3) negatively charged nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 hours with each kind of nanoparticles. Their cellular uptake was assessed by fluorimetry and cellular responses were evaluated in terms of cytotoxicity (loss of cell membrane integrity, determined by the Lactate DeHydrogenase (LDH) assay), pro-inflammatory TNF-<∝> production and oxidative stress (Reactive Oxygen Species (ROS) generation). Results showed that sterically stabilized nanoparticles were more internalized and induced more pro-inflammation than charge stabilized nanoparticles. However, these latter, even less internalized triggered more oxidative stress. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and cytotoxicity.