期刊
NATURE CHEMISTRY
卷 11, 期 11, 页码 1041-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41557-019-0328-4
关键词
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资金
- EPSRC [EP/G006792, EP/F034210/1, EP/P030572/1, EP/P001459/1, EP/N010825/1, EP/N010825]
- MRC [G0701062]
- Royal Society [NF160307, NF151429]
- Leverhulme Trust
- National Science Foundation of China (NSFC) [21701113, 21525105, 21471164, 21778079]
- 973 Program [2015CB856301]
- Fundamental Research Funds for the Central Universities
- ERC [GA 681679 PhotoMedMet]
- French Government [ANR-10-IDEX-0001-02 PSL]
- Sun Yat-sen University Startup fund [75110-18841213]
- EPSRC [EP/P030572/1, EP/P001459/1, EP/N010825/1] Funding Source: UKRI
- MRC [G0701062] Funding Source: UKRI
Hypoxic tumours are a major problem for cancer photodynamic therapy. Here, we show that photoredox catalysis can provide an oxygen-independent mechanism of action to combat this problem. We have designed a highly oxidative Ir(III) photocatalyst, [Ir(ttpy)(pq)CI]PF6 ([1]PF6, where 'ttpy' represents 4'-(p-tolyl)-2,2':6',2 ''-terpyridine and 'pq' represents 3-phenylisoquinoline), which is phototoxic towards both normoxic and hypoxic cancer cells. Complex 1 photocatalytically oxidizes 1,4-dihydronicotinamide adenine dinucleotide (NADH)-an important coenzyme in living cells-generating NAD center dot radicals with a high turnover frequency in biological media. Moreover, complex 1 and NADH synergistically photoreduce cytochrome c under hypoxia. Density functional theory calculations reveal pi stacking in adducts of complex 1 and NADH, facilitating photoinduced single-electron transfer. In cancer cells, complex 1 localizes in mitochondria and disrupts electron transport via NADH photocatalysis. On light irradiation, complex 1 induces NADH depletion, intracellular redox imbalance and immunogenic apoptotic cancer cell death. This photocatalytic redox imbalance strategy offers a new approach for efficient cancer phototherapy.
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