Nanoplastics enhance florfenicol toxicity by disturbing detoxification and metabolic processes in nematodes

Nanoplastics (NPs) and antibiotics are ubiquitous contaminants that frequently coexist and undergo interactions in various environments. While their combined toxicity is known to depend on NP physicochemical properties, the mechanistic basis of their toxicological interactions, particularly how surface charge and particle size modulate combined effects, remains unclear. Using <i>Caenorhabditis elegans</i> as a model, we investigated the combined toxicity of florfenicol (FF) with four polystyrene nanoplastics (PS-NPs) differing in size (100 nm (PS-100) and 500 nm (PS-500)) and surface modification (-NH₂ (PS-NH₂) and -COOH (PS-COOH)), and the mechanisms were explained through integrated analyses of bioaccumulation, detoxification gene expression, and metabolic homeostasis. The results revealed that while the NP coexposures did not significantly alter analyte bioaccumulation in <i>C. elegans</i>, they suppressed detoxification genes, with PS-100 and PS-NH₂ causing more severe dysfunction than PS-500 or PS-COOH. Metabolomic perturbations in the combined exposures were 2.12- to 4.86-fold greater than those in the FF exposure alone, with different NPs exacerbating oxidative stress and toxicity <i>via</i> divergent metabolic pathway disruptions. Building upon these transcriptomic and metabolomic mechanisms, the positively charged PS-NH₂ and smaller-sized PS-100 amplified FF toxicity, as quantified through both survival rate and body length reductions, more than their negatively charged (PS-COOH) and larger-sized (PS-500) counterparts. The findings advance the mechanistic understanding of NP-antibiotic interactions, supporting evidence-based environmental risk assessment of co-occurring pollutants.