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Nano Research 2023, 16(7): 9752-9759 https://doi.org/10.1007/s12274-023-5588-z
Research Article | Issue | Published: 13 March 2023

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

Show Author's Information Yuxing Jiang1,2,§,  Hongtao Rong1,§,  Yifan Wang3,§,  Shange Liu3,  Peng Xu2,  Zhen Luo2,  Lamei Guo2,  Tao Zhu1( ),  Hongpan Rong3,  Dingsheng Wang4,  Jiatao Zhang3( ),  Yu Yi2,5( ),  Hao Wang2,5( )
Tianjin Medical University General Hospital, Tianjin 300052, China
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
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
Department of Chemistry, Tsinghua University, Beijing 100084, China
University of Chinese Academy of Sciences, Beijing 100049, China

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

Keywords:
spinal cord injury, anti-inflammation, neuroprotection, reactive oxygen and nitrogen species, single-atom catalysis
Topics:
Biomaterials Enzymes
Cite this article:
Jiang Y, Rong H, Wang Y, et al. Single-atom cobalt nanozymes promote spinal cord injury recovery by anti-oxidation and neuroprotection. Nano Research, 2023, 16(7): 9752-9759. https://doi.org/10.1007/s12274-023-5588-z
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Abstract Full text Electronic supplementary material About this article

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 (O2•−), 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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Electronic supplementary material
About this article

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

Show Author's information Yuxing Jiang1,2,§, Hongtao Rong1,§, Yifan Wang3,§, Shange Liu3, Peng Xu2, Zhen Luo2, Lamei Guo2, Tao Zhu1( ), Hongpan Rong3, Dingsheng Wang4, Jiatao Zhang3( ), Yu Yi2,5( ), Hao Wang2,5( )
Tianjin Medical University General Hospital, Tianjin 300052, China
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
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
Department of Chemistry, Tsinghua University, Beijing 100084, China
University of Chinese Academy of Sciences, Beijing 100049, China

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

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 (O2•−), 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.

Keywords: spinal cord injury, anti-inflammation, neuroprotection, reactive oxygen and nitrogen species, single-atom catalysis

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Publication history
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Acknowledgements

Publication history

Received: 19 December 2022
Revised: 04 February 2023
Accepted: 18 February 2023
Published: 13 March 2023
Issue date: July 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

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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