Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles

Abstract

Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) 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.

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

“…Excessive use of exogenous metals may cause potentially adverse effects on human health, including acute and chronic damage. 283 The enhanced permeability and retention (EPR) effect is influenced by factors such as the nature of the nanomedicine itself, tumor growth, and patient heterogeneity. These factors make drug targeting inefficient and make it difficult to achieve complete drug enrichment in the tumor.…”

“…After applying very small IONPs (ESIONPs) to a zebrafish model, Zhaojie Lyu et al found that ESIONPs may be neurotoxic and induce ferroptosis. 283 The abnormal accumulation of iron ions may increase the risk of early degenerative neurological diseases. Therefore, the biosafety and selectivity of nanomedicines for therapeutic use remain highly questionable.…”