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Low-dose exposure to graphene oxide significantly increases the metal toxicity to macrophages by altering their cellular priming state

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Abstract

Owing to the novel physicochemical properties of graphene, materials such as graphene oxide (GO) are being developed for applications in various fields such as biomedicine. Nonetheless, considerable knowledge gaps still exist regarding the impact of GOs on environmental health and safety (EHS). Thus far, its secondary toxicity, synergistic effects, and mal-adaption have not been focused much upon. Here, we show that at low concentrations (that did not directly result in significant cytotoxicity), GO could greatly enhance metal toxicity in macrophages by altering their cellular priming state. Specifically, GO caused impairments to the cellular morphology and membrane integrity of macrophages, and remarkably enhanced the cellular uptake of Cd and other non-essential metal ions (such as Hg and Gd). Furthermore, upon low-dose GO pre-treatment, the uptake of Cd at a non-toxic concentration brought about a remarkable amount of oxidative stress in macrophages, and ultimately resulted in increased cell death. Mechanistic investigations illustrated that GO pre-treatment triggered cell death through apoptosis because of Cd exposure. Overall, this study’s results reveal a new path for understanding the impact of GOs on EHS through the perspective of its synergistic and secondary effects, previously unidentified mechanisms via which nanomaterials might pose detrimental effects on organisms.

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Acknowledgements

This work was supported by the National Basic Research Program of China (No. 2014CB932000), the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB14000000), the National Natural Science Foundation of China (Nos. 21425731, 21425729, 21637004, 21407169, 21077128 and 21577097), the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No. 2017KJ209) and China Postdoctoral Science Foundation funded project (No. H037).

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Author notes

  1. Jianqiang Zhu and Ming Xu contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China

    Jianqiang Zhu, Ming Xu, Ming Gao & Sijin Liu

  2. Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China

    Jianqiang Zhu, Zhihong Zhang & Yong Xu

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Ming Xu, Ming Gao & Sijin Liu

  4. College of Environmental Science and Engineering, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin, 300350, China

    Fanfan Wang & Wei Chen

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  1. Jianqiang Zhu
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Correspondence to Wei Chen or Sijin Liu.

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12274_2018_1996_MOESM1_ESM.pdf

Low-dose exposure to graphene oxide significantly increases the metal toxicity to macrophages by altering their cellular priming state

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Zhu, J., Xu, M., Wang, F. et al. Low-dose exposure to graphene oxide significantly increases the metal toxicity to macrophages by altering their cellular priming state. Nano Res. 11, 4111–4122 (2018). https://doi.org/10.1007/s12274-018-1996-x

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