Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans

Abstract

We present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in Caenorhabditis elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated. The role of oxidative stress was confirmed by gene expression analysis and by synchrotron Fourier Transform infrared microscopy based on the higher tissue oxidation of NP-treated animals. The observed transcriptional modulation of key signaling pathways such as MAPK and Wnt suggests that SPIONs might be endocytosed by clathrin-mediated processes, a putative mechanism of nanotoxicity which deserves further mechanistic investigations.

Keywords:

• Toxicogenomics
• nanotoxicity
• C. elegans
• iron oxide nanoparticles
• protein corona

Acknowledgements

We acknowledge Víctor Fuentes for his collaboration in the synthesis of gold nanoparticles. SRS acknowledges core funding from King’s College London and access and support from the King’s Genomics Centre. SR-μFTIR experiments were performed at MIRAS beamline at ALBA Synchrotron with the collaboration of ALBA staff.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

C. elegans N2 and E. coli OP50 were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This research was partially funded by the Spanish Ministry of Economy and Competitiveness co-funded by European Social Funds, through project MAT2015-64442-R, the ‘Severo Ochoa’ Program for Centers of Excellence in R&D (SEV- 2015-0496), the Ramon y Cajal program (AL, RyC-2010-06082), FPU program (LGM, FPU12/05549), SY acknowledges Chinese Fundamental Research Funds for the Central Universities (21616306), the Generalitat de Catalunya (2014SGR213), People Program of the European Commission (grant agreement no. 303630, co-funded by the European Social Fund), the COST Action GENIE (Action No. BM1408-A).