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J. Hazard. Mater., Available online 1 December 2025, 140670 | https://doi.org/10.1016/j.jhazmat.2025.140670
SiO2 Nanoparticles Disrupt Neurodevelopmental Processes in Human Midbrain Organoids in a Redox-Suppressed, Non-Cytotoxic Manner
Seohyun Kim a,b,1, Youngsun Lee a,b,1, Hyang-Ae Lee c,d, Mi-Ok Lee a,b
aKorea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea
bKRIBB School of Bioscience, University of Science and Technology, Daejeon, 34113, Republic of Korea
cCenter for Biomimetic Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea
dSchool of Korea Institute of Toxicology, University of Science & Technology (UST), Daejeon 34113, Republic of Korea
Corresponding authors: Hyang-Ae Lee, Mi-Ok Lee
aKorea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea
bKRIBB School of Bioscience, University of Science and Technology, Daejeon, 34113, Republic of Korea
cCenter for Biomimetic Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea
dSchool of Korea Institute of Toxicology, University of Science & Technology (UST), Daejeon 34113, Republic of Korea
Corresponding authors: Hyang-Ae Lee, Mi-Ok Lee
Abstract
Silicon dioxide nanoparticles (SiO₂-NPs) are widely used in food, cosmetics, and biomedical products and cross the placental barrier, raising concerns about their potential developmental toxicity. Although previous studies have documented cytotoxic and oxidative effects of SiO₂-NPs in adult tissues, their influence on early human neurodevelopment remains poorly understood. Here, we employed human midbrain organoids (mBOs) derived from pluripotent stem cells to investigate SiO₂-NP–induced neurodevelopmental alterations during dopaminergic lineage formation. Exposure during this critical window reduced organoid growth, suppressed neural progenitor proliferation, and downregulated dopaminergic markers, while overall neuronal populations were preserved. Remarkably, these changes occurred without apoptosis but were accompanied by diminished intracellular ROS, impaired calcium signaling, and activation of astrocytic and inflammatory pathways. Phospho-kinase profiling and RNA sequencing further revealed suppression of calcium- and redox-dependent signaling networks alongside metabolic and inflammatory reprogramming. Collectively, these findings identify a non-cytotoxic, redox-suppressed mechanism by which SiO₂-NPs perturb neuronal maturation and connectivity, highlighting the developmental vulnerability of the human midbrain to nanoparticle exposure.
논문정보
- Research article
- 2025년 12월 (BRIC 등록일 2025-12-02)
- 국내 연구진
- 생명과학 > 세포생물학
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