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Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells.

ABSTRACT: The increasing use of nanoparticles (NPs) in various applications entails the need for reliable assessment of their potential toxicity for humans. Originally, studies concerning the toxicity of NPs focused on cytotoxic and genotoxic effects, but more recently, attention has been paid to epigenetic changes induced by nanoparticles. In the present research, we analysed the DNA methylation status of genes related to inflammation and apoptosis as well as the expression of miRNAs related to these processes in response to silver (AgNPs), gold (AuNPs), and superparamagnetic iron oxide nanoparticles (SPIONs) at low cytotoxic doses in HepG2 cells. There were no significant differences between treated and control cells in the DNA methylation status. We identified nine miRNAs, the expression of which was significantly altered by treatment with nanoparticles. The highest number of changes was induced by AgNPs (six miRNAs), followed by AuNPs (four miRNAs) and SPIONs (two miRNAs). Among others, AgNPs suppressed miR-34a expression, which is of particular interest since it may be responsible for the previously observed AgNPs-mediated HepG2 cells sensitisation to tumour necrosis factor (TNF). Most of the miRNAs affected by NP treatment in the present study have been previously shown to inhibit cell proliferation and tumourigenesis. However, based on the observed changes in miRNA expression we cannot draw definite conclusions regarding the pro- or anti-tumour nature of the NPs under study. Further research is needed to fully elucidate the relation between observed changes in miRNA expression and the effect of NPs observed at the cellular level. The results of the present study support the idea of including epigenetic testing during the toxicological assessment of the biological interaction of nanomaterials.

SUBMITTER: Brzoska K

PROVIDER: S-EPMC6479689 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells.

Brzóska Kamil K Grądzka Iwona I Kruszewski Marcin M

Materials (Basel, Switzerland) 20190329 7

The increasing use of nanoparticles (NPs) in various applications entails the need for reliable assessment of their potential toxicity for humans. Originally, studies concerning the toxicity of NPs focused on cytotoxic and genotoxic effects, but more recently, attention has been paid to epigenetic changes induced by nanoparticles. In the present research, we analysed the DNA methylation status of genes related to inflammation and apoptosis as well as the expression of miRNAs related to these pro ...[more]

PMID: 30934809

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Project description:Au and Fe nanoparticles and their conjugates with the drug methotrexate were obtained by an environmentally safe method of metal-vapor synthesis (MVS). The materials were characterized by transmission and scanning electron microscopy (TEM, SEM), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering using synchrotron radiation (SAXS). The use of acetone as an organic reagent in the MVS makes it possible to obtain Au and Fe particles with an average size of 8.3 and 1.8 nm, respectively, which was established by TEM. It was found that Au, both in the NPs and the composite with methotrexate, was in the Au0, Au+ and Au3+ states. The Au 4f spectra for Au-containing systems are very close. The effect of methotrexate was manifested in a slight decrease in the proportion of the Au0 state-from 0.81 to 0.76. In the Fe NPs, the main state is the Fe3+ state, and the Fe2+ state is also present in a small amount. The analysis of samples by SAXS registered highly heterogeneous populations of metal nanoparticles coexisting with a wide proportion of large aggregates, the number of which increased significantly in the presence of methotrexate. For Au conjugates with methotrexate, a very wide asymmetric fraction with sizes up to 60 nm and a maximum of ~4 nm has been registered. In the case of Fe, the main fraction consists of particles with a radius of 4.6 nm. The main fraction consists of aggregates up to 10 nm. The size of the aggregates varies in the range of 20-50 nm. In the presence of methotrexate, the number of aggregates increases. The cytotoxicity and anticancer activity of the obtained nanomaterials were determined by MTT and NR assays. Fe conjugates with methotrexate showed the highest toxicity against the lung adenocarcinoma cell line and Au nanoparticles loaded with methotrexate affected the human colon adenocarcinoma cell line. Both conjugates displayed lysosome-specific toxicity against the A549 cancer cell line after 120 h of culture. The obtained materials may be promising for the creation of improved agents for cancer treatment.

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Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells.

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Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells.

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