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Rational Design of Genetically Engineered Mitochondrial-Targeting Nanozymes for Alleviating Myocardial Ischemic-Reperfusion Injury

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    Rational Design of Genetically Engineered Mitochondrial-Targeting Nanozymes for Alleviating Myocardial Ischemic-Reperfusion Injury
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    • Xiangyun Zhang
      Xiangyun Zhang
      School of Medicine, Nankai University, Tianjin 300071, China
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
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    • Qiqi Liu
      Qiqi Liu
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Qiqi Liu
    • Rongping Zhao
      Rongping Zhao
      School of Medicine, Nankai University, Tianjin 300071, China
      More by Rongping Zhao
    • Zhihua Pang
      Zhihua Pang
      School of Medicine, Nankai University, Tianjin 300071, China
      Department of Cardiology, Tianjin Union Medical Center, Tianjin 300121, China
      More by Zhihua Pang
    • Weiyu Zhang
      Weiyu Zhang
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Weiyu Zhang
    • Tianyi Qi
      Tianyi Qi
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Tianyi Qi
    • Mingsheng Zhu
      Mingsheng Zhu
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Mingsheng Zhu
    • Helong Kang
      Helong Kang
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Helong Kang
    • Meng Qian
      Meng Qian
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Meng Qian
    • Yajuan Wan
      Yajuan Wan
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Yajuan Wan
    • Rui Wang
      Rui Wang
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Rui Wang
    • Shufang Wang
      Shufang Wang
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      More by Shufang Wang
      Orcidhttps://orcid.org/0000-0002-0335-6024
    • Xinglu Huang*
      Xinglu Huang
      Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
      State Key Laboratory of Medicinal Chemical Biology, Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
      *Email: [email protected]
      More by Xinglu Huang
      Orcidhttps://orcid.org/0000-0002-9378-7425
    • Jie Zhuang*
      Jie Zhuang
      School of Medicine, Nankai University, Tianjin 300071, China
      *Email: [email protected]
      More by Jie Zhuang
      Orcidhttps://orcid.org/0009-0006-4481-0672
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    Nano Letters

    Cite this: Nano Lett. 2025, 25, 2, 663–672
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    https://doi.org/10.1021/acs.nanolett.4c04462
    Published December 9, 2024
    Copyright © 2024 American Chemical Society
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    Abstract

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    The development of mitochondria-targeting nanozymes holds significant promise for treating myocardial ischemia-reperfusion (IR) injury but faces significant biological barriers. To overcome these obstacles, we herein utilized genetically engineered ferritin nanocages (i.e., imFTn) to develop mitochondria-targeting nanozymes consisting of three ferritin subunit assembly modules: an IR-injured cardiomyocyte-targeting module, a lysosome-escaping module, and a mitochondria-targeting module. Using imFTn as a nanozyme platform, we developed nanozymes capable of efficiently catalyzing the l-Arg substrate to produce NO. The imFTn-Ru exhibits NO-generating activities, reduces mitochondrial reactive oxygen species generation, inhibits mitochondrial permeability transition pore opening, and enhances mitochondrial membrane potential. Furthermore, imFTn-Ru provides synergistic effects by specifically targeting myocardial IR-injured tissues, facilitating their accumulation in mitochondria, and protecting mitochondria against myocardial IR-induced injury in both in vitro and in vivo models. This study underscores a rational approach to designing nanozymes for targeting specific subcellular organelles in the treatment of IR injury.

    Copyright © 2024 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.nanolett.4c04462.

    • Flow cytometry gating strategies; active targeting ability of FTn in IR hearts; representative confocal images of the subcellular colocalization of various FTn nanoparticles; catalytic recyclability of imFTn-Ru in NO generation; confocal images and flow cytometry analysis of O2•– and ONOO– level in HL-1 cells; H&E staining of different organs isolated from the mice to evaluate systemic toxicities; confocal images and quantitative analysis of O2•– levels in the IR-damaged area; plasmid construction of FTn and FTn variants (PDF)

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    Cited By

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    This article is cited by 1 publications.

    1. Fanyong Yan, Dongyang Liu, Baojuan Zhao, Yu Wang, Yidi Wang, Shangpeng Yang, Shanshan Li. Intervening with nanozymes in aging-related diseases: Strategies for restoring mitochondrial function. Biomaterials Advances 2025, 169 , 214193. https://doi.org/10.1016/j.bioadv.2025.214193
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    Nano Letters

    Cite this: Nano Lett. 2025, 25, 2, 663–672
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.nanolett.4c04462
    Published December 9, 2024
    Copyright © 2024 American Chemical Society
    Request reuse permissions

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