A digestive system microphysiological platform for assessment of internal-exposure risks and metabolic disease mechanisms induced by multi-size nano-plastics

Nano-plastics (NPs) are emerging hazardous environmental contaminants that pose health risks with size-dependent toxic effects and are potential risk factors for hepatocellular carcinoma (HCC) and lipid metabolism disorders including non-alcoholic fatty liver disease (NAFLD). However, their underlying molecular mechanisms remain unclear. To shed more light on the causes of these risks, we developed a digestive system microphysiological platform (DS-MPP) for simulating dynamic internal-exposure of multi-size NPs in the gastrointestinal tract and liver. Multi-omics analysis based on DS-MPP revealed hepatic cells are more sensitive to 72 μg/day NPs than gastrointestinal mucosa cells. Specifically, 50 nm NPs disrupt phospholipid metabolism, promote diacylglycerol (DG) accumulation, convert more DG to phosphatidic acid (PA) than triacylglycerol (TG), thus facilitating endocytic vesicles production. Meanwhile, it can active tumorigenesis related pathway mTOR, inducing HCC marked by CAB39. Moreover, 500 nm NPs promote NAFLD by inducing insulin resistance pathways and decreasing PLD1 expression. Our results demonstrate the mechanism of disease and metabolic disorders induced by NPs vary depending on particle size. DS-MPP is a reliable platform for evaluating risk of dynamic NPs exposure and elucidating mechanisms of related metabolic diseases. This platform provides a promising method for health risk assessment caused by environmental pollutants. [Display omitted] •Developed a feasible DS-MPP to simulate nano-plastic dynamic internal exposure.•Nano-plastics can disrupt hepatic lipid metabolism and may increase cancer risk.•Metabolic abnormalities induced by nano-plastics exhibit a size-dependent effect.•50 nm nano-plastics stimulate endocytosis, mTOR signaling, and result in HCC.•500 nm nano-plastics induce insulin resistance signaling, contributing to NAFLD.