[Exposure Pathways of Polystyrene Nanoplastics Mediate Their Cellular Distribution and Toxicity].

Objective: To investigate whether exposure pathways influence the distribution pattern and toxicity of polystyrene nanoplastics (PSNPs) in hepatic cells. Methods: Male C57BL/6J wild-type healthy mice aged 6 to 8 weeks old and weighed 18 to 22 g were administered with PSNPs via gavage or tail vein injection. Then, we tracked PSNPs distribution in the major organs of mice via an Results: IVIS revealed predominant hepatic accumulation of PSNPs regardless of exposure pathways via intragastric gavage or tail vein injection. Immunofluorescence/TEM demonstrated exposure pathway-dependent cellular distribution: intragastric PSNPs were localized mainly in hepatocytes, while intravenous PSNPs were accumulated in Kupffer cells. Changes in particle size (300 nm vs. 70 nm) did not alter the cellular distribution pattern, while 70 nm PSNPs injected via the portal vein accumulated in Kupffer cells, which suggested that the cell-type-specific distribution of PSNPs in the liver was independent of PSNPs size and might be related to the transport of PSNPs in the gastrointestinal tract. Flow cytometry showed that PSNPs uptake by AML-12 was time-dependent and that the underlying endocytosis mechanism involved pathways mediated by clathrin ( Conclusion: Exposure pathways mediate the hepatic cell-type-specific distribution of PSNPs, thereby altering the downstream toxicological consequences induced by exposure to PSNPs.