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 (SiO 2 NPs) caused unexpected cardiovascular toxic effects. However, the toxicities of SiO 2 NPs in other organs have warranted further investigation. To confirm the accumulation of SiO 2 NPs in the brain, we introduced SiO 2 NPs with different diameters into mice via intranasal instillation (INI) and intravenous injection (IVI) in parallel. We found that SiO 2 NPs may target the brain through both olfactory and systemic routes, but the size of SiO 2 NPs and delivery routes both significantly affected their brain accumulation. Surprisingly, while equivalent SiO 2 NPs were found in the brain regions, brain lesions were distinctly much higher in INI than in the IVI group. Mechanistically, we showed that SiO 2 NPs introduced via INI induced brain apoptosis and autophagy, while the SiO 2 NPs introduced via IVI only induced autophagy in the brain.