Novel Approach for Characterizing Exposure and Response to Engineered Nanomaterials in the Gut

Consumer safety concerns are mounting as engineered nanoparticlesENPsare increasingly being incorporated into consumable productssuch as fooddrugsand personal care productsWhile toxicological effects of inhaled and skin contacting ENPs have been evaluatedvery little is known about the short term and long term effects of ingested ENPsTo evaluate the safety and possible toxic effects of ENPs on the gastrointestinalGIepitheliumhuman primary cell based screening assays are urgently neededSpecificallyusing more compleximmunocompetent in vitro systems that mimic the native tissue microenvironment would greatly advance our ability to accurately assess the intestinal toxicity of ingested ENPsThe overall objective of this proposal is to develop an in vitro test methodology that accurately determines the toxicological profile of ENPs following intestinal exposureTo achieve this goalwe will utilize MatTek Corporation s highly differentiatedorganotypic EpiIntestinal tissue model containing epithelial cellsfibroblastsand immune cellsDuring Phasea prediction model will be developed to identify ENPs that are likely to cause gastrointestinalGIirritationinflammation or genotoxicityor perturb homeostasisbarrier functionin the GI tractSince repeat exposure to ENPs is implicated in nanotoxicityboth acute and chronic exposure conditions will be simulatedSuch a human cell basedin vitro GI toxicity model which recapitulates the human small intestine will have enormous market utility for screening ingestible nanomaterials used in the pharmaceutical and food industries Adverse effects in the gastrointestinal tract are major concerns for engineered nanoparticlesENPsincorporated into foodsdrugs and consumer care productsThis project will develop an in vitro small intestine tissue based assay method to identify biomarkers that can better predict the effects of ENPs on the human gastrointestinal tractThe multicellular nature of the reconstructed tissue model allows investigation of cellularmolecularand immunological mechanisms of gastrointestinal related adverse effectsWe anticipate that this project will allow us to develop a highly sensitive and reliable set of biomarkers to screen ENPs intended for oral administration