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 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.

Co-Exposure of Ambient Particulate Matter and Airborne Transmission Pathogens: The Impairment of the Upper Respiratory Systems

“…33 In addition, model FPMs with simple compositions, such as silica (SiO 2 ) particles, aluminum oxide (Al 2 O 3 ) particles, and microplastics (fluorescent polystyrene) particles, were chosen to represent the real PMs according to the major components of dust samples and model FPMs applied in previous studies. 33 , 40 , 41 The SEM images showed that the five model particles appeared in different morphologies, but all had a size of approximately 2 μm ( Figure S1 ), consistent with the size of real FPMs. In specific, the SiO 2 and FPS particles were spheres with smooth surfaces, and BC particles appeared as sheet-like morphologies.…”

“…Hereby, different types of FPMs, that is, dust, SiO 2 particles, BC, microplastic particles, and Al 2 O 3 particles were chosen to represent the real FPMs because these compositions were commonly found in atmospheric environments. , The dust sample is a mixture of ambient fine particles containing silica (69–77%), aluminum oxide (8–14%), and other minerals taken from the real environment and is commonly applied to represent real PMs . In addition, model FPMs with simple compositions, such as silica (SiO 2 ) particles, aluminum oxide (Al 2 O 3 ) particles, and microplastics (fluorescent polystyrene) particles, were chosen to represent the real PMs according to the major components of dust samples and model FPMs applied in previous studies. ,, The SEM images showed that the five model particles appeared in different morphologies, but all had a size of approximately 2 μm (Figure S1), consistent with the size of real FPMs. In specific, the SiO 2 and FPS particles were spheres with smooth surfaces, and BC particles appeared as sheet-like morphologies.…”

“…aeruginosa, on the upper respiratory tract as well as the systematic reaction. Airborne FPMs could load with pathogens, such as bacteria and viruses, while floating and then facilitate pathogen transmission and infection. , Recent studies have often applied nasal instillation or intratracheal administration to study the health effects of air pollution. ,,,, These exposure methods could simulate inhalation exposure and refer to detrimental outcomes somehow. However, the particles should be suspended in the solution before administration, and this process apparently is not realistic.…”

“… 3 , 10 Recent studies have often applied nasal instillation or intratracheal administration to study the health effects of air pollution. 28 , 30 , 40 , 47 , 56 These exposure methods could simulate inhalation exposure and refer to detrimental outcomes somehow. However, the particles should be suspended in the solution before administration, and this process apparently is not realistic.…”

Using Chicken Embryos to Identify the Key Determinants of Nanoparticles for the Crossing of Air–Blood Barriers

“…In mammals, inhaled NPs were found to elicit severe pulmonary diseases, such as inflammation, , fibrosis, − and tumor metastasis . In addition, epidemiological studies have indicated that airborne NPs may penetrate lung tissue, circulate in blood, and affect other organs, such as the heart, liver, kidney, and brain, causing cardiovascular or neurological diseases . Ibanez et al visualized the particle distributions in extrapulmonary organs of mice that received aerosol inhalation of UO 4 NPs and detected elemental uranium in the mouse brain after 4 h .…”