Amplified toxic effects of nanoplastic composite norfloxacin on liver cells in mice: Mechanistic insights and multiscale evaluation

Abstract

The concomitant presence of nanoplastics (NPs) and antibiotics in environmental matrices demands urgent investigation into their combined toxicity, however, the underlying mechanisms remain poorly understood. Here, we employed a multiscale strategy to clarify the combined toxicity and mechanisms of NPs and norfloxacin (NOR) in primary murine hepatocytes. Specifically, co-exposure triggered a 59.0 % reduction in cell viability, exceeding individual treatments (NOR alone: 43.2 %), while amplifying intracellular reactive oxygen species (ROS) generation by 60.1 % compared to individual NOR treatment. NPs promoted NOR bioaccumulation via carrier-mediated transport, thereby aggravating oxidative imbalance through SOD suppression (24.3 % inhibition) and lipid peroxidation (48.3 % MDA elevation). Molecular analyses revealed NPs-NOR complexes destabilized the secondary structure of CAT, increasing α-Helix (2.2 %) content, and docking simulations identified NOR binding to residues. These findings mechanistically link NPs-antibiotic interactions to amplified toxicity via oxidative stress and conformational disruption, highlighting NPs as critical modulators of pollutant bioavailability. This work advances predictive frameworks for composite toxicity, underscores the need to prioritize risk assessment of co-contaminants in environmental and biomedical contexts.