Interaction of gold nanoparticles and nickel(II) sulfate affects dendritic cell maturation

Abstract

Despite many investigations have focused on the pristine toxicity of gold nanoparticles (GNPs), little is known about the outcome of co-exposure and interaction of GNPs with heavy metals which can possibly detoxify or potentiate them. Here, the combined exposure of nickel (II) sulfate (NiSO₄) and GNPs on the maturation response of dendritic cells (DCs) was explored. Exposure to GNPs or NiSO₄ separately induced cell activation. When cells were exposed to a mixture of both, however, the observed cell activation pattern indicated a competitive rather than an additive effect of both inducers with levels similar to those induced by NiSO₄ alone. Quantification of the GNP uptake by DCs demonstrated a significant decrease in intracellular gold content during co-incubation with NiSO₄. An extensive physiochemical characterization was performed to determine the interaction between GNPs and NiSO₄ in the complex physiological media using nanoparticle tracking analyses, disc centrifugation, UV–visible spectroscopy, ICP-MS analyses, zeta potential measurements, electron microscopy, and proteomics. Although GNPs and NiSO₄ did not directly interact with each other, the presence of NiSO₄ in the physiological media resulted in changes in GNPs' charge and their associated protein corona (content and composition), which may contribute to a decreased cellular uptake of GNPs and sustaining the nickel-induced DC maturation. The presented results provide new insights in the interaction of heavy metals and NPs in complex physiological media. Moreover, this study highlights the necessity of mixture toxicology, since these combined exposures are highly relevant for human subjection to NPs and risk assessment of nanomaterials.

Keywords:

• Co-exposure
• dendritic cells
• gold nanoparticles
• nickel sulfate

Acknowledgements

Authors would like to thank Raymond Kemps for the assistance with the scanning electron microscopy, Wilfried Bursten for the ICP-MS analyses and Dr. Nathalie Lambrechts for the advice concerning the sensitization potential of NiSO₄.

Declaration of interest

The authors declare that there are no conflicts of interest. This work was funded by the FP7 project QualityNano under Grant agreement no. INFRA-2010-262163 and FP7 Future Nano Needs under Grant agreement no. NMP4-LA-2013-604602. Sarah Deville is supported by a fellowship of VITO and UHasselt (BOF). SFI Industry fellowship (15/IFA/3057) awarded to Marco P. Monopoli is also acknowledged.

Supplementary material available online

Supplementary Figures S1–S5 and Table S1.