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

Nanoparticles (NPs) can make their way to the brain and cause in situ 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 via 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 via INI induced brain apoptosis and autophagy, while the SiO2 NPs introduced via IVI only induced autophagy in the brain.