Silica nanoparticles antagonize while titania nanoparticles synergize silver nanoparticle toxicity in zebrafish

This study investigated the individual and combined toxicity of silver (AgNPs), titanium dioxide (TiO₂NPs), and silicon dioxide nanoparticles (SiO₂NPs) in zebrafish (Danio rerio), with emphasis on acute/chronic mortality, oxidative stress, bioaccumulation, and histopathology. In vitro stability tests showed that SiO₂NPs reduced AgNP stability more strongly than TiO₂NPs, leading to greater sedimentation and a lower silver concentration in the water. In vivo acute toxicity assays revealed that SiO₂NPs antagonized, whereas TiO₂NPs synergized, AgNPs-induced lethality. During chronic exposure, the highest whole-body Ag accumulation occurred in fish co-exposed to AgNPs and SiO₂NPs. Notably, artificial neural network modeling predicted a late-phase decline in whole-body silver burden during the uptake phase, particularly in the AgNPs-H + SiO₂NPs treatment, although this prediction did not constitute direct evidence of active excretion. During chronic exposure, both SiO₂NPs and TiO₂NPs reduced AgNP-associated mortality, but their effects on tissue damage and oxidative stress were divergent: AgNPs + TiO₂NPs exacerbated liver damage and suppressed antioxidant defenses, whereas AgNPs + SiO₂NPs attenuated gill and intestinal damage and enhanced antioxidant responses. Our results underscore that co-exposure to nanoparticles can fundamentally alter their stability, bioavailability, and toxicological outcomes, with effects ranging from antagonistic to synergistic depending on the nanoparticle combination and target organ.