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

Abstract

International audienceSilica 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 (PEG) 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 hours 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 positive charged nanoparticle, were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticles types. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and biological toxicity

Preferential binding of positive nanoparticles on cell membranes is due to electrostatic interactions: A too simplistic explanation that does not take into account the nanoparticle protein corona

“…A neutral form was also produced. Depending on their surface charge the nanoparticles were referred to as NP(--), NP(-), NP(0), NP(+) and NP(++) [43]. They were characterized just after their synthesis (in water) and in the cell culture medium used for our subsequent nanotoxicological assays: DMEM supplemented with 10% fetal calf serum (referred to as DMEMc, c standing for complete).…”

Impact of silica nanoparticle surface chemistry on protein corona formation and consequential interactions with biological cells

“…The total fluorescence of NP was first measured in each well, then the fluorescence of NP in supernatant (1), adsorbed to cell membrane (2) and internalized by cells (3) were discriminated by a "trypan blue (TB) quenching" as previously described [34][35][36][37][38]. TB is known for its ability to "turn off" the green fluorescence emitted by FITC allowing the discrimination of internalized NP from those adhering to plasma membrane [39].…”

Biological and environmental surface interactions of nanomaterials: characterization, modeling, and prediction

“…In a typical aqueous biological environment rich in electrolytes, surface charge renders formation of stable suspension for nanoparticles, and gives them different affinities to different molecules present. In some cases, positively charged particles were found to have higher uptake rate due to their higher affinity to the negatively charged cell membrane . Other studies indicated that rate of uptake could be directly related to the absolute value of charge, regardless of the sign .…”