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纳米二氧化硅的脑内蓄积和毒性特征:粒径和暴露途径的影响

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

机构信息

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Rd, Beibei District, Chongqing 400715, China.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Rd, Haidian District, Beijing 100085, China.

出版信息

Environ Sci Technol. 2022 Jun 21;56(12):8319-8325. doi: 10.1021/acs.est.1c07562. Epub 2022 May 16.

DOI:10.1021/acs.est.1c07562
PMID:35576522
Abstract

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

摘要

纳米颗粒(NPs)可以进入大脑并造成损伤,这是纳米材料应用和空气传播颗粒物暴露的一个关注点。我们最近的研究表明,呼吸暴露于二氧化硅纳米颗粒(SiO NPs)会引起意想不到的心血管毒性作用。然而,SiO NPs 在其他器官中的毒性仍需要进一步研究。为了确认 SiO NPs 在大脑中的积累,我们平行地将不同直径的 SiO NPs 通过鼻腔内滴注(INI)和静脉注射(IVI)引入小鼠体内。我们发现,SiO NPs 可能通过嗅觉和全身途径靶向大脑,但 SiO NPs 的大小和输送途径都显著影响其在大脑中的积累。令人惊讶的是,尽管大脑区域中存在等效的 SiO NPs,但 INI 组中的脑损伤明显高于 IVI 组。从机制上讲,我们表明通过 INI 引入的 SiO NPs 诱导了脑凋亡和自噬,而通过 IVI 引入的 SiO NPs 仅在脑内诱导了自噬。

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