An osmium-peroxo complex for photoactive therapy of hypoxic tumors
Nong Lu,
Zhihong Deng,
Jing Gao,
Chao Liang,
Haiping Xia (hpxia@xmu.edu.cn) and
Pingyu Zhang (p.zhang6@szu.edu.cn)
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Nong Lu: Shenzhen University
Zhihong Deng: Southern University of Science and Technology
Jing Gao: Southern University of Science and Technology
Chao Liang: Shenzhen University
Haiping Xia: Southern University of Science and Technology
Pingyu Zhang: Shenzhen University
Nature Communications, 2022, vol. 13, issue 1, 1-11
Abstract:
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.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29969-z
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DOI: 10.1038/s41467-022-29969-z
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