Surface chemistry and size-related particle attributes shape lipidomic responses to polystyrene micro- and nanoplastics in zebrafish liver cells.

MICRO: and nano-plastics (MNPs) are emerging environmental pollutants, yet the influence of surface functionalization on their hepatotoxicity remains poorly understood. In this study, zebrafish liver (ZFL) cells were exposed plain and surface-functionalized polystyrene microplastics (1 μm) and nanoplastics (50 nm) to assess their effects on cell viability, generation of reactive oxygen species (ROS), lipidomic responses, and gene expression. As a complementary analysis, UV-treated particles were evaluated on cell viability and ROS production. While most treatments did not impair cellular viability or trigger extensive transcriptional responses, UV photodegradation produced only transient changes in ROS levels, with minor increases relative to controls. MP-NH2 caused a marked accumulation of cholesterol esters, accompanied by reduced microsomal triglyceride transfer protein (mtp) transcript abundance, suggesting perturbation of sterol metabolism. In contrast, plain nanoplastics selectively increased ether-linked phosphatidylcholines, suggesting altered membrane organization. Overall, these findings indicate that size-related particle attributes and surface chemistry, particularly aminated MPs and plain NPs, are associated with distinct lipidomic responses in ZFL cells, and highlight lipidomics as a sensitive approach for detecting early biochemical perturbations following MNP exposure.