Investigating the Impact of Carboxylated Polystyrene Nanoplastics in the Liver Using Cell Lines and Precision‐Cut Liver Slices

BACKGROUND AND AIMS: Increasing reports of plastic accumulation in human tissue have raised concerns about potential adverse health outcomes. Evidence of negative effects of nanoplastics is heterogeneous and provides limited insights into the underlying pathogenic toxicity mechanisms in humans. METHODS: In the present study, carboxylate-modified fluorescently labelled polystyrene nanoparticles (PS NPs) were used to investigate uptake and cytotoxicity in three different hepatic models of varying complexity, including HepG2 cells, IHH cells, and human precision-cut liver slices (hPCLS). RESULTS: The results show model- and dose-dependent effects on hepatocytes. 74.2% ± 13.4% of the IHH cells showed PS NPs uptake at 0.1 μg/mL, which is considerably lower than the estimated plastic concentration in human blood (1.8-4.7 μg/mL). The viability of IHH cells decreased to 10.6% ± 9.1% after exposure to 100 μg/mL for 48 h. Early signs of hepatic injury were found in hPCLS at high concentrations. No changes were observed in the redox state and mitochondrial respiratory parameters of HepG2 cells after exposure. CONCLUSION: The PS NPs exposure experiments show uptake across all three hepatic models and toxic effects in IHH cells and hPCLS. Overall, the study highlights the need for physiologically relevant human tissue models to understand the impact of nanoplastic pollution on human health.