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Uptake of Intact Copper Oxide Nanoparticles Causes Acute Toxicity in Cultured Glial Cells

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Abstract

Copper oxide nanoparticles (CuO-NPs) dispersions are known for their high cell toxic potential but contaminating copper ions in such dispersions are a major hurdle in the investigation of specific nanoparticle-mediated toxicity. In order to distinguish between the adverse effects exhibited by CuO-NPs and/or by contaminating ionic copper, the membrane-impermeable copper chelator bathocuproine disulfonate (BCS) was added in a low molar ratio (20% of the total copper applied) in order to chelate the copper ions that had been released extracellularly from the CuO-NPs before or during the incubation. Physicochemical characterization of synthesized CuO-NPs revealed that the presence of this low concentration of BCS did not alter the size or zeta potential of the CuO-NPs. Application of CuO-NPs to C6 glioma cells and primary astrocytes induced a concentration- and temperature-dependent copper accumulation which was accompanied by a severe loss in cell viability. The adverse consequences of the CuO-NP application were not affected by the presence of 20% BCS, while the copper accumulation and cell toxicity observed after application of ionic copper were significantly lowered in the presence of BCS. These results demonstrate that for the experimental conditions applied the adverse consequences of an exposure of cultured glial cells to dispersions of CuO-NPs are mediated by accumulated NPs and not caused by the uptake of contaminating copper ions.

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Acknowledgements

Arundhati Joshi would like to thank the Hans-Böckler Foundation for a PhD fellowship at the Graduate School NanoCompetence at the University of Bremen, Germany.

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Authors and Affiliations

  1. Center for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO. Box 330440, 28334, Bremen, Germany

    Arundhati Joshi, Kshitija Jog & Ralf Dringen

  2. Center for Environmental Research and Sustainable Technology, Leobener Strasse, 28359, Bremen, Germany

    Arundhati Joshi & Ralf Dringen

  3. Fraunhofer Institute for Manufacturing Technology and Advanced Materials, Wiener Strasse 12, 28359, Bremen, Germany

    Karsten Thiel

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  1. Arundhati Joshi
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Correspondence to Ralf Dringen.

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Joshi, A., Thiel, K., Jog, K. et al. Uptake of Intact Copper Oxide Nanoparticles Causes Acute Toxicity in Cultured Glial Cells. Neurochem Res 44, 2156–2169 (2019). https://doi.org/10.1007/s11064-019-02855-9

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