Brain Accumulation and Toxicity Profiles of Silica Nanoparticles: The Influence of Size and Exposure Route

Abstract

Nanoparticles (NPs) can make their way to the brain and cause <i>in situ</i> damage, which is a concern for nanomaterial application and airborne particulate matter exposure. Our recent study indicated that respiratory exposure to silica nanoparticles (SiO₂ NPs) caused unexpected cardiovascular toxic effects. However, the toxicities of SiO₂ NPs in other organs have warranted further investigation. To confirm the accumulation of SiO₂ NPs in the brain, we introduced SiO₂ NPs with different diameters into mice <i>via</i> intranasal instillation (INI) and intravenous injection (IVI) in parallel. We found that SiO₂ NPs may target the brain through both olfactory and systemic routes, but the size of SiO₂ NPs and delivery routes both significantly affected their brain accumulation. Surprisingly, while equivalent SiO₂ NPs were found in the brain regions, brain lesions were distinctly much higher in INI than in the IVI group. Mechanistically, we showed that SiO₂ NPs introduced <i>via</i> INI induced brain apoptosis and autophagy, while the SiO₂ NPs introduced <i>via</i> IVI only induced autophagy in the brain.