The increased use of engineered nanomaterials in pharmaceuticals, materials science, and consumer products has raised questions regarding the potential risks of these nanoproducts to human and ecological health. Environmental applications for in situ site remediation and water treatment can provide a route for human exposure and are especially appropriate for toxicity evaluation. This research investigated the response of bacteria and mammalian nerve cells to commercially available zero-valent iron (ZVI) and TiO₂ nanoparticles. In the first part of the research, immortalized mouse microglia (BV2) responded to non-cytotoxic concentrations of TiO₂ with a rapid and sustained release of reactive oxygen species (ROS) consistent with both the oxidative burst and interference with electron transport. Transmission electron microscopy documented engulfment of aggregates of nanosized particles. A second study found that extended exposure of microglia to TiO₂ produced loss of nuclear staining consistent with DNA degradation. Gene expression analysis in microglia indicated up-regulation of inflammatory, apoptotic, and cell cycling pathways and down-regulation of energy metabolism following TiO ₂ exposure. TiO₂ did not produce cytotoxicity in immortalized dopaminergic neurons (N27), but primary cultures with mixed neuronal and glial populations showed neuronal loss and microscopic evidence of neuronal apoptosis, indicating potential involvement of glia in neuronal cytotoxicity.

Experiments with Escherichia coli K-12 indicated that ZVI, but not TiO₂, caused significant viability loss in the absence of photoactivation. Gene expression analysis found that ZVI induced genes in the oxidative phosphorylyation pathway, primarily those associated with electron transport. This result was corroborated by increased respiration following ZVI exposure, consistent with increased activity of the electron transport chain. Neither effect was observed after TiO₂ exposure. Electron microscopy documented localization of ZVI nanoparticles on the cell surface, potentially interfering with maintenance of the proton-motive force necessary for ATP generation. Consistent with its lack of toxicity, TiO ₂ induced cell maintenance functions and down-regulated stress response pathways, and did not associate with cell membranes. Considering the results from all studies, it appears that ZVI and TiO₂ provoke different responses in bacterial and mammalian cells and may act via separate modes of action.