Gastrointestinal digestion potentiates nanoplastic-induced intestinal barrier dysfunction and macrophage-driven inflammation.

Nanoplastics (NPs) are emerging environmental contaminants that are pervasive in ecosystems and consumer products. When ingested orally, they may potentially cause enteric diseases. Although NPs undergo physicochemical alterations through environmental and biological transformations, which can modulate their toxicity in the gastrointestinal tract, most studies have overlooked these changes, as well as the uncertainties regarding their interaction and inflammatory mechanisms among different intestinal cells after entering the intestine. In this research, a Transwell™ co-culture model consisting of differentiated Caco-2 intestinal epithelial monolayers and Raw264.7 macrophages was employed to investigate the uptake, translocation, and inflammatory effects of food-relevant NPs, namely polystyrene (PS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET), following in vitro gastrointestinal digestion. The results demonstrated that gastrointestinal digestion modified the physicochemical properties of PS, PET, and PVC NPs, promoting agglomeration, an increase in surface negative charge, and the formation of protein corona. These changes enhanced cellular uptake by both Caco-2 epithelial cells and Raw264.7 macrophages. Consequently, digested NPs caused more significant barrier disruption and stronger inflammatory responses, characterized by the activation of NF-κB/NLRP3 and an elevated release of IL-6 and IL-1β. These findings underscore the crucial importance of considering realistic digestive transformations and material-specific characteristics in future toxicity assessments of NPs, offering vital insights for evaluating the enteritis risks associated with ingested NPs.