The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells

Abstract

A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although dissolved zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn2+ complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution.

Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus pictus) embryos

“…This indicates that soluble copper is not the only source of internalized copper, further supporting the observation that nano-CuO aggregates are being internalized. As such, nano-CuO may follow the ''Trojan horse''-type mechanism (Studer et al, 2010), delivering high concentrations of copper when aggregates dissolve inside the cell due to significantly lower cytoplasmic pH (Johnson & Epel, 1981), creating copper hot-spots, as has been demonstrated for other metal oxide NMs (Gilbert et al, 2012;Xia et al, 2008). Based on the differences in dissolution rates measured in FSW, it is reasonable to hypothesize that the NMs may have accentuated differences in dissolution rates inside the cells where pH is lower and there is higher protein concentration (Studer et al, 2010), resulting in higher solubility and toxicity of synthesized nano-CuO compared with commercial nano-CuO.…”

An alternative approach to studying the effects of ZnO nanoparticles in cultured human lymphocytes: combining electrochemistry and genotoxicity tests

“…Gilbert et al (41) have already evidenced that ZnO NPs enter cells undissolved. Particles are taken up through endocytosis, primarily via caveolae, and end up in intracellular vesicles (42).…”

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

“…The fates of ZnO nanoparticles in human bronchial epithelial cells (BEAS-2B) were determined by scanning transmission X-ray microscopy and X-ray absorption near-edge structure analysis; 41 the nanoparticles are taken up by cells in particulate forms, then completely and rapidly dissolve inside cells, generating Zn 2+ ligated by thiol groups. This is consistent with the in vivo ZnO nanoparticle fate determined by Paek et al 26 The bioavailability fate of isotope-labeled ZnO nanoparticles was traced by coherent anti-Stokes Raman scattering and scanning transmission electron microscopy with energy dispersive X-ray spectroscopy in mud shrimp (Corophium volutator); 42 ionic zinc from particles in an aqueous environment was determined primarily to contribute to the uptake and bioavailability fate of ZnO nanoparticles.…”