Altered locomotion and anxiety after exposure to SiO2 nanoparticles in larval zebrafish

Nanoparticles (NP) have been driving the rapid advancement of nanomedicines in recent decades. However, their wide application also raises safety concerns, particularly their neurotoxicity due to their ability to cross the blood-brain barrier and accumulate in the brain, which remains largely underexplored. Here, we used silica nanoparticles (SiO₂ NP) as a model to study the neurotoxicity of nanomedicine, based on their general features and functionalities. Using the light/dark preference behavioral assays of larval zebrafish, we focused on the neurotoxic consequences of exposure to an array of low concentrations of SiO₂ NP, which reflected real-world conditions compared to previous studies, and examined the effect of different exposure durations. We observed dose-dependent and temporally sensitive changes in locomotor activities and elevated anxiety-related behaviors after exposure. Strikingly, exposed animals exhibited biphasic alteration: hypo-locomotion after 24-hour exposure and hyper-locomotion after 48-hour exposure. Our work provided real-world relevant behavioral insights, and highlighted the biphasic response and the temporal sensitivity of the SiO₂ NP neurotoxicity. These findings underscore the potential neurotoxic risks of nanomedicine applications and emphasize the urgent need for further research into NP-associated neurotoxicity and public awareness.