Genotoxicity of mesoporous silica nanoparticles in human embryonic kidney 293 cells

摘要

Mesoporous silica nanoparticles (MSNs) have been widely evaluated for their potential use as carriers for cancer diagnosis and therapy. Understanding the toxicity of MSNs is crucial to their biomedical applications. Although several groups have reported the cytotoxicity of MSNs, the genotoxicity (inducing genetic aberrations) of MSNs in normal human cells has not been extensively investigated. Gene amplification and mutation may initiate and promote carcinogenesis, and changes in mRNA expression can affect normal human physical functions. In this study, human embryonic kidney 293 (HEK293) cells were treated overnight with MSNs at a concentration of 120 mu g/mL. The cells were assayed with fluorescent in situ hybridization to check for chromosome changes and gene amplification. Mutations in the epidermal growth factor receptor 1 (EGFR1) and KRAS genes were checked with DNA sequencing. The effects of MSNs on mRNA expression were investigated with an Agilent human mRNA microarray. No chromosomal alterations or gene mutations in EGFR or KRAS were observed in the control HEK293 cells or HEK293 cells exposed to MSNs. The microarray analysis showed that MSNs significantly altered gene expression. The expression of 579 genes was upregulated and that of 1263 genes was downregulated in HEK293 cells treated with MSNs compared with the control HEK293 cells. Our findings suggest that exposure to MSNs is genotoxic to normal human cells, leading to changes in the expression of some genes. This genotoxicity may cause cellular dysfunction and certain benign diseases. We have not shown that MSN exposure induces serious genotoxicity involving carcinogenesis. Copyright (c) 2015 John Wiley & Sons, Ltd.