Toxicity effects of nanomaterial exposure to human intestinal cells

Engineered nanomaterials are increasingly used in consumer products. While the potential of these products is promising, it is not known what latent toxic effects nanomaterials may have on human health. The methods reported here describe a system in which the intestinal lining is mimicked (Caco-2 human intestinal cell line) and provides an environment in which nanomaterials can be applied. The first investigation describes non-lethal effects of titanium dioxide nanoparticles, while the second investigation describes a method to study the nanotoxicity of non-aggregated quantum dots (QDs) on the model epithelium.;The first investigation studied the possible pathways by which titanium dioxide nanoparticles could cross the epithelium layer by employing both toxicity and mechanistic studies. This investigation provides evidence that titanium dioxide nanoparticles cross the epithelial lining of the intestinal model by transcytosis, albeit at low levels. Titanium dioxide was able to penetrate into and through the cells without disrupting junctional complexes. To monitor the epithelial integrity, transepithelial electrical resistance (TEER) was employed and determined low concentrations (10mg/L) of titanium dioxide did not disrupt epithelial integrity. In addition, titanium dioxide nanoparticles altered microvillar organization on the apical surface of the epithelium as well as induced a rise in intracellular-free calcium. Although titanium dioxide does not cause cell death, the implication of other non-lethal effects could lead to undesired outcomes (i.e., disease, malnutrition, etc.).;The second investigation assessed whether the epithelial integrity was breached because of QD exposure. QDs were suspended in calcium/magnesium-free phosphate buffered saline to study non-aggregated QDs. To maintain cell integrity, normal cell culture conditions were retained below the epithelium to provide necessary nutrients and ions. Toxicity studies show that the nano-sized QDs caused disruption in the epithelium monolayer and cell death at 0.1 mg/L of QDs. This toxicity was caused by the nano-size of the QDs rather than the cadmium ions or the sodium thioglycolate capping ligands. Aggregated QDs did not cause toxicity as measured by TEER.;Results reported here can be applied to modeling systems to help predict toxicity of future, undiscovered nanomaterials and can easily be transitioned into high-throughput assays that are rapid, reproducible, and affordable.