Enhanced toxicity of silver nanoparticles in transgenic Caenorhabditis elegans expressing amyloidogenic proteins

Abstract

The increasing number of applications of silver nanoparticles (AgNP) prompted us to assess their toxicity in vivo. We have investigated their effects on wild type and transgenic Caenorhabditis elegans (C. elegans) strains expressing two prototypic amyloidogenic proteins: β2-microglobulin and Aβ peptide_3–42. The use of C. elegans allowed us to highlight AgNP toxicity in the early phase of the worm’s life cycle (LC₅₀ survival, 0.9 µg/ml). A comparative analysis of LC₅₀ values revealed that our nematode strains were more sensitive to assess AgNP toxicity than the cell lines, classically used in toxicity tests. Movement and superoxide production in the adult population were significantly affected by exposure to AgNP; the transgenic strains were more affected than the wild type worms. Our screening approach could be applied to other types of nanomaterials that can enter the body and express any nanostructure-related bioactivities. We propose that C. elegans reproducing the molecular events associated with protein misfolding diseases, e.g. Alzheimer’s disease and systemic amyloidosis, may help to investigate the specific toxicity of a range of potentially harmful molecules. Our study suggests that transgenic C. elegans may be used to predict the effect of chemicals in a “fragile population”, where an underlying pathologic state may amplify their toxicity.

• Amyloidosis
• C. elegans
• nanoparticles
• nanotoxicology

Acknowledgements

We wish to thank Stefania Grandi for dynamic light scattering analysis, Elia Di Schiavi for assistance with the stabilization of the transgenic C. elegans strain expressing β2 -m and the Caenorhabditis Genetics Center for providing N2 and CL2120 strains.

Declaration of interest

The authors declare no conflicts of interest. This work was supported by Grants from Italian Ministry of Health, Research and Education to T.C. and L.M.; Project FIRB RBFR109EOS to S.G.; INBB (National Institute of Biostructures and Biosystems) to V.B. and M.S.; Telethon (grant no. GG14127) to V.B. and CARIPLO Foundation (Rif. 2011-2096 to L.M. and 2013-0964 to S.G.).