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Uptake and Toxicity of Copper Oxide Nanoparticles in C6 Glioma Cells

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Abstract

Copper oxide nanoparticles (CuO-NPs) are frequently used for many technical applications, but are also known for their cell toxic potential. In order to investigate a potential use of CuO-NPs as a therapeutic drug for glioma treatment, we have investigated the consequences of an application of CuO-NPs on the cellular copper content and cell viability of C6 glioma cells. CuO-NPs were synthesized by a wet-chemical method and were coated with dimercaptosuccinic acid and bovine serum albumin to improve colloidal stability in physiological media. Application of these protein-coated nanoparticles (pCuO-NPs) to C6 cells caused a strong time-, concentration- and temperature-dependent copper accumulation and severe cell death. The observed loss in cellular MTT-reduction capacity, the loss in cellular LDH activity and the increase in the number of propidium iodide-positive cells correlated well with the specific cellular copper content. C6 glioma cells were less vulnerable to pCuO-NPs compared to primary astrocytes and toxicity of pCuO-NPs to C6 cells was only observed for incubation conditions that increased specific cellular copper contents above 20 nmol copper per mg protein. Both cellular copper accumulation as well as the pCuO-NP-induced toxicity in C6 cells were prevented by application of copper chelators, but not by endocytosis inhibitors, suggesting that liberation of copper ions from the pCuO-NPs is the first step leading to the observed toxicity of pCuO-NP-treated glioma cells.

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Acknowledgments

Aaron Schultz would like to thank the Deakin University, School of Life and Environmental Science for the New Ideas Research Award and the Company of Biologists for the Disease Models and Mechanisms Travelling Fellowship. Arundhati Joshi and Kathrin Faber would like to thank the Hans-Böckler Foundation for a PhD fellowship in the Graduate School NanoCompetence at the University of Bremen.

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

    Arundhati Joshi, Wiebke Rastedt, Kathrin Faber, Felix Bulcke & Ralf Dringen

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

    Arundhati Joshi, Wiebke Rastedt, Kathrin Faber, Felix Bulcke & Ralf Dringen

  3. School of Life and Environmental Sciences, Centre for Molecular and Medical Research, Deakin University, Locked Bag 20000, Geelong, VIC, 3220, Australia

    Aaron G. Schultz

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  1. Arundhati Joshi
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Correspondence to Ralf Dringen.

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Joshi, A., Rastedt, W., Faber, K. et al. Uptake and Toxicity of Copper Oxide Nanoparticles in C6 Glioma Cells. Neurochem Res 41, 3004–3019 (2016). https://doi.org/10.1007/s11064-016-2020-z

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