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Functionalized single-walled carbon nanotubes cause reversible acute lung injury and induce fibrosis in mice

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Abstract

Nanotechnology is one of today’s most promising technological developments, but safety concerns raise questions about its development. Risk assessments of nanomaterials during occupational exposure are crucial for their development. Here, we assessed the lung toxicity of functionalized single-walled carbon nanotube (f-SWCNT) exposure in C57BL/6 mice, elucidated the underlying molecular mechanism, and evaluated the self-repair ability and lung fibrosis of the mice. Soluble f-SWCNTs were administered to mice. After 18 h or 14 days, the lung histopathology, bronchoalveolar lavage fluid, lung edema, vascular permeability, and PaO2 levels were evaluated, and biochemical and immunostaining tests were also performed. We found that some f-SWCNTs could induce acute lung injury (ALI) in mice via proinflammatory cytokine storm signaling through the NF-κB pathway in vivo. We illustrated that corticosteroid treatments could ameliorate the ALI induced by the f-SWCNTs in mice. Surprisingly, the ALI was almost completely reversed within 14 days, while mild to moderate fibrosis, granuloma, and DNA damage remained in the mice at day 14. Our studies indicate potential remedies to address the growing concerns about the safety of nanomaterials. In addition, we notify that the type of functional groups should be considered in nanomedicine application as differently functionalized SWCNTs generated different effects on the lung toxicity.

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Acknowledgments

The authors thank Xiangwu Ju for help with the illustrations and gratefully acknowledge Prof. Haiyan Xu, Dr. Jie Meng, Dr. Jian Liu, Weiqi Zhang, and Peng Zhang for their helpful suggestions and kind assistance. This work was supported by the National Natural Science Foundation of China (30625013 and 30721063) and the Ministry of Science and Technology of China (2009ZX10004-308, 2009CB522105, and 2011CB933504).

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The authors declare no conflict of interest related to this study.

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Authors and Affiliations

  1. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Chengyu Jiang, Room 460, No. 5 Dongdansantiao, Beijing, 100005, China

    Yanli Zhang, Jiejie Deng, Yanxu Zhang, Feng Guo, Chenggang Li, Zhen Zou, Wen Xi, Jun Tang, Yang Sun, Peng Yang, Zongsheng Han & Chengyu Jiang

  2. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    Dangsheng Li

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  1. Yanli Zhang
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  2. Jiejie Deng
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  5. Chenggang Li
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  10. Peng Yang
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  11. Zongsheng Han
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  12. Dangsheng Li
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  13. Chengyu Jiang
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Corresponding author

Correspondence to Chengyu Jiang.

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Y. Zhang and J. Deng contributed equally to this work.

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Zhang, Y., Deng, J., Zhang, Y. et al. Functionalized single-walled carbon nanotubes cause reversible acute lung injury and induce fibrosis in mice. J Mol Med 91, 117–128 (2013). https://doi.org/10.1007/s00109-012-0940-x

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  • DOI: https://doi.org/10.1007/s00109-012-0940-x

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