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An osmium-peroxo complex for photoactive therapy of hypoxic tumors

Author

Listed:
  • Nong Lu

    (Shenzhen University)

  • Zhihong Deng

    (Southern University of Science and Technology)

  • Jing Gao

    (Southern University of Science and Technology
    the Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University)

  • Chao Liang

    (Shenzhen University)

  • Haiping Xia

    (Southern University of Science and Technology)

  • Pingyu Zhang

    (Shenzhen University)

Abstract

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O2•− upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

Suggested Citation

  • Nong Lu & Zhihong Deng & Jing Gao & Chao Liang & Haiping Xia & Pingyu Zhang, 2022. "An osmium-peroxo complex for photoactive therapy of hypoxic tumors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29969-z
    DOI: 10.1038/s41467-022-29969-z
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    References listed on IDEAS

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    1. Johannes Karges & Shi Kuang & Federica Maschietto & Olivier Blacque & Ilaria Ciofini & Hui Chao & Gilles Gasser, 2020. "Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Le Jiang & Ning Kon & Tongyuan Li & Shang-Jui Wang & Tao Su & Hanina Hibshoosh & Richard Baer & Wei Gu, 2015. "Ferroptosis as a p53-mediated activity during tumour suppression," Nature, Nature, vol. 520(7545), pages 57-62, April.
    3. Chao Liang & Jiaen Xie & Shuangling Luo & Can Huang & Qianling Zhang & Huaiyi Huang & Pingyu Zhang, 2021. "A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
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