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Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma

Author

Listed:
  • Hanchen Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Nicolás Montesdeoca

    (Ruhr-University Bochum)

  • Dongsheng Tang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ganghao Liang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Minhui Cui

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Chun Xu

    (The University of Queensland)

  • Lisa-Marie Servos

    (Ruhr-University Bochum)

  • Tiejun Bing

    (ICE Bioscience)

  • Zisis Papadopoulos

    (Ruhr-University Bochum)

  • Meifang Shen

    (Beijing University of Chemical Technology)

  • Haihua Xiao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yingjie Yu

    (Beijing University of Chemical Technology)

  • Johannes Karges

    (Ruhr-University Bochum)

Abstract

The majority of anticancer agents have a reduced or even complete loss of a therapeutic effect within hypoxic tumors. To overcome this limitation, research efforts have been devoted to the development of therapeutic agents with biological mechanisms of action that are independent of the oxygen concentration. Here we show the design, synthesis, and biological evaluation of the incorporation of a ruthenium (Ru) catalyst into polymeric nanoreactors for hypoxic anticancer therapy. The nanoreactors can catalyze the oxidation of glutathione (GSH) to glutathione disulfide (GSSG) in hypoxic cancer cells. This initiates the buildup of reactive oxygen species (ROS) and lipid peroxides, leading to the demise of cancer cells. It also stimulates the overexpression of the transient receptor potential melastatin 2 (TRPM2) ion channels, triggering macrophage activation, leading to a systemic immune response. Upon intravenous injection, the nanoreactors can systemically activate the immune system, and nearly fully eradicate an aggressive osteosarcoma tumor inside a mouse model.

Suggested Citation

  • Hanchen Zhang & Nicolás Montesdeoca & Dongsheng Tang & Ganghao Liang & Minhui Cui & Chun Xu & Lisa-Marie Servos & Tiejun Bing & Zisis Papadopoulos & Meifang Shen & Haihua Xiao & Yingjie Yu & Johannes , 2024. "Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53646-y
    DOI: 10.1038/s41467-024-53646-y
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    References listed on IDEAS

    as
    1. Joan J. Soldevila-Barreda & Isolda Romero-Canelón & Abraha Habtemariam & Peter J. Sadler, 2015. "Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    2. Minfeng Huo & Liying Wang & Yu Chen & Jianlin Shi, 2017. "Tumor-selective catalytic nanomedicine by nanocatalyst delivery," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
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