Evaluating the toxicity of silicon dioxide nanoparticles on neural stem cells using RNA-Seq

Abstract

Neural stem cells are characterized by self-renewal and multipotency, and a capacity to regenerate in response to brain injury or neurodegenerative disease. Silicon dioxide nanoparticles (SiO₂ NPs) are novel materials, which enable the delivery of specific payloads to stem cells; for example, genes or proteins, to enable cell-fate manipulation, or tracer materials, to enable in vivo tracing. However, little is known about the dose-dependent cytotoxicity of SiO₂ NPs, and how exposure to SiO₂ NPs changes mRNA expression profiles in neural stem cells. In this study, a mouse C17.2 neural stem cell line was treated with 90 nm monodisperse fluorescein isothiocyanate-SiO₂ NPs at 0, 100, 200 and 400 μg mL⁻¹ for 48 hours. Internalization of SiO₂ NPs was observed in C17.2 cells in a dose-dependent manner. SiO₂ NP exposure induced apoptosis and inhibited cell proliferation in the C17.2 cell line at dosage levels of 200 μg mL⁻¹ and above. Microscopically, mitochondrial swelling and cristae fracture were observed. Furthermore, next generation RNA sequencing (RNA-Seq) indicated that high-dose SiO₂ NP exposure specifically inhibited transcription of glutathione-S-transferase (GST) genes, including GSTM1, GSTM7 and GSTT1. These results suggest that application of high-dose SiO₂ NPs to the nervous system may cause neurotoxicity, induce apoptosis and reduce neural stem cell proliferation by inhibiting GST gene expression.