An in vitro investigation of the impact of nanomaterials on the human intestine

In recent years, research on nanotechnology has been in exponential growth, with exploitation of NMs across an array of sectors including agriculture, food, medicine, cosmetics, textiles and electronics. Currently, research on nanomaterial (NM) toxicity is dominated by studies that have investigated the impact of NMs on the body (and in particular the lungs) following inhalation. However, as the ingestion of NMs is increasing, and thus the Gastrointestinal (GI) tract may be exposed to NMs via direct oral ingestion, mucocillary escalator clearance (following inhalation) and hand to mouth contact. For example, copper oxide (CuO) NMs are used as anti-microbials, and may leach into food from food contact materials (e.g. packaging). The aim of this study was to investigate the toxicity of NMs to the intestine in vitro, using human Caco-2 intestinal cells. Culturing of Caco-2 cells for 15-21 days, leads to their spontaneous differentiation to mature intestinal-like cells. Whilst the use of differentiated cells is more expensive and time consuming, these cells better resemble the structure and function of intestinal cells in vivo. Thus, we compared the response of differentiated and undifferentiated cells to CuO NMs in vitro. In this study, we have demonstrated that CuO NMs caused disruption of intestinal barrier integrity, which increased the translocation of Cu across the intestinal cell monolayer. CuO NMs also stimulated the production of the pro-inflammatory cytokine IL-8. The toxicity of CuO NMs was greater to undifferentiated cells, suggesting that differentiated cells were less sensitive to CuO NMs. We have also shown that differentiated Caco-2 cells are a powerful in vitro model that can be used to screen the impacts of ingested NMs on the GI tract.