Neurotoxicity of Titanium Dioxide Nanoparticles: A Comprehensive Review

The increasing use of titanium dioxide nanoparticles (TiO₂ NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO₂ NPs on both humans and the environment. Notably, TiO₂ NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO₂ NPs in different species and in vitro models. Following exposure, TiO₂ NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO₂ NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO₂ NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO₂ NPs. However, a systematic comparison of the neurotoxic effects of TiO₂ NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO₂ NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO₂ NPs.