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Single-atom cobalt nanozymes promote spinal cord injury recovery by anti-oxidation and neuroprotection

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Abstract

Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury (SCI). Antioxidant therapies that reduce the reactive oxygen and nitrogen species (RONS) overgeneration and inflammation are proved promising for improving the outcomes. However, efficient and long-lasting antioxidant therapy to eliminate multiple RONS with effective neuroprotection remains challenging. Here, a single-atom cobalt nanozyme (Co-SAzyme) with a hollow structure was reported to reduce the RONS and inflammation in the secondary injury of SCI. Among SAzymes featuring different single metal-N sites (e.g., Mn, Fe, Co, Ni, and Cu), this Co-SAzyme showed a versatile property to eliminate hydrogen peroxide (H2O2), superoxide anion (O ·−2 ), hydroxyl radical (·OH), nitric oxide (·NO), and peroxynitrite (ONOO−) that overexpressed in the early stage of SCI. The porous hollow structure also allowed the encapsulation and sustained release of minocycline for neuroprotection in synergy. In vitro results showed that the Co-SAzyme reduced the apoptosis and pro-inflammatory cytokine levels of microglial cells under oxidative stress. In addition, the Co-SAzyme combined with minocycline achieved remarkable improved functional recovery and neural repairs in the SCI-rat model.

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Acknowledgements

This research was financially supported by the National Natural Science Foundation of China (Nos. 22175048, 22005027, and 51890892) and Tianjin Health Commission (No. ZC20175). We thank the assistance from 1W1B beamline at Beijing Synchrotron Radiation Facility in XAFS measurements and Analysis & Testing Center of Beijing Institute of Technology in TEM observations. The animal study protocol was approved by the Institutional Animal Care and Use Committee at the National Center for Nanoscience and Technology (NCNST).

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  1. Yuxing Jiang, Hongtao Rong, and Yifan Wang contributed equally to this work.

Authors and Affiliations

  1. Tianjin Medical University General Hospital, Tianjin, 300052, China

    Yuxing Jiang, Hongtao Rong & Tao Zhu

  2. National Center for Nanoscience and Technology, CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Beijing, 100190, China

    Yuxing Jiang, Peng Xu, Zhen Luo, Lamei Guo, Yu Yi & Hao Wang

  3. Beijing Key Laboratory of Construction-Tailorable Advanced Functional Materials and Green Applications, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Materials Science & Engineering, School of Chemistry and Chemical Engineering, Institute of Engineering Medicine, Beijing Institute of Technology, Beijing, 100081, China

    Yifan Wang, Shange Liu, Hongpan Rong & Jiatao Zhang

  4. Department of Chemistry, Tsinghua University, Beijing, 100084, China

    Dingsheng Wang

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

    Yu Yi & Hao Wang

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  1. Yuxing Jiang
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Correspondence to Tao Zhu, Jiatao Zhang, Yu Yi or Hao Wang.

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Jiang, Y., Rong, H., Wang, Y. et al. Single-atom cobalt nanozymes promote spinal cord injury recovery by anti-oxidation and neuroprotection. Nano Res. 16, 9752–9759 (2023). https://doi.org/10.1007/s12274-023-5588-z

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