title: Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts.
abstract: Gold nanoparticles (AuNPs) are currently used in several fields including biomedical applications, although no conclusive information on their cytotoxicity is available. For this reason this work has investigated the effects of AuNPs in vitro on Balb/3T3 mouse fibroblasts. Results obtained exposing cells for 72 h to AuNPs 5 and 15 nm citrate stabilized, revealed cytotoxic effects only for AuNPs 5 nm at concentration ≥ 50 μM if measured by colony forming efficiency (CFE). To understand the differences in cytotoxicity observed for the two AuNPs sizes, we investigated the uptake and the intracellular distribution of the nanoparticles. By TEM it was observed that 5 and 15 nm AuNPs are internalized by Balb/3T3 cells and located within intracellular endosomal compartments. Quantification of the uptake by ICP-MS showed that AuNPs internalization enhanced even up to 72 h. Disruption of the actin cytoskeleton was evident, with cell footprints narrow and contracted; effects more remarkable in cells exposed to 5 nm AuNP. The mechanism of NPs cell internalization was investigated using immunocytochemistry and western blot. No significant effect was observed in the expression level of caveolin, while reduction of the expression and degradation of the clathrin heavy chain was observed in cells exposed for 72 h to AuNPs.
authors.affiliation: Nanobiosciences Unit, Joint Research Centre, Institute for Health and Consumer Protection, European Commission, Via E. Fermi 2749, 21027 Ispra, VA, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Coradeghini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gioria
authors.forename: César Pascual
authors.initials: CP
authors.lastname: García
authors.forename: Paola
authors.initials: P
authors.lastname: Nativo
authors.forename: Fabio
authors.initials: F
authors.lastname: Franchini
authors.forename: Douglas
authors.initials: D
authors.lastname: Gilliland
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponti
authors.forename: François
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D033922:Clathrin Heavy Chains / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006046:Gold / Q000633:toxicity*; D007150:Immunohistochemistry; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010316:Particle Size
chemical_list: D051242:Caveolin 1; D033922:Clathrin Heavy Chains; D006046:Gold