Lyu Zhaojie, Kou Yao, Fu Yao, Xie Yuxuan, Yang Bo, Zhu Hongjie, Tian Jing
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China.
Center for Automated and Innovative Drug Discovery, School of Medicine, Northwest University, Xi'an, China.
Front Genet. 2024 May 17;15:1402771. doi: 10.3389/fgene.2024.1402771. eCollection 2024.
Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (FeO or FeO) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3 nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.
氧化铁纳米颗粒是一种由氧化铁（FeO或Fe₂O₃）组成的纳米材料，在磁共振成像中有广泛应用。与氧化铁纳米颗粒相比，直径约3纳米的极小氧化铁纳米颗粒（ESIONPs）由于尺寸更小，可改善成像性能。然而，目前尚无关于ESIONPs对人体潜在毒性作用的报道。在本研究中，我们将ESIONPs应用于斑马鱼模型，并使用RNA测序技术对48小时、72小时、96小时和120小时斑马鱼胚胎中的差异表达基因（DEGs）进行加权基因共表达网络分析（WGCNA）。确定了与神经毒性和铁死亡相关的关键枢纽基因，进一步实验还表明ESIONPs损害了斑马鱼的神经元和肌肉发育，并诱导了铁死亡，导致氧化应激、细胞凋亡和炎症反应。在此，我们首次通过WGCNA分析了ESIONPs的潜在毒性作用。我们的研究表明，ESIONPs可能具有神经毒性并可诱导铁死亡，而铁离子的异常积累可能增加早期退行性神经疾病的风险。
