Targeted photoredox catalysis in cancer cells.
- Huang H School of Pharmaceutical Science (Shenzhen), Sun Yat-sen University, Guangzhou, China.
- Banerjee S Department of Chemistry, University of Warwick, Coventry, UK.
- Qiu K MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China.
- Zhang P College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China.
- Blacque O Department of Chemistry, University of Zurich, Zurich, Switzerland.
- Malcomson T School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
- Paterson MJ School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
- Clarkson GJ Department of Chemistry, University of Warwick, Coventry, UK.
- Staniforth M Department of Chemistry, University of Warwick, Coventry, UK.
- Stavros VG Department of Chemistry, University of Warwick, Coventry, UK.
- Gasser G Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Health and Life Sciences, Laboratory for Inorganic Chemical Biology, Paris, France. gilles.gasser@chimieparistech.psl.eu.
- Chao H MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China. ceschh@mail.sysu.edu.cn.
- Sadler PJ Department of Chemistry, University of Warwick, Coventry, UK. p.j.sadler@warwick.ac.uk.
- 2019-09-25
Published in:
- Nature chemistry. - 2019
Antineoplastic Agents
Biocatalysis
Cell Death
Coordination Complexes
Cytochromes c
Density Functional Theory
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Conformation
NAD
Neoplasms
Oxidation-Reduction
Photochemical Processes
Tumor Hypoxia
English
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)Cl]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• 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 π 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.
- Language
-
- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/s41557-019-0328-4
- PMID 31548671
- Persistent URL
- https://sonar.ch/global/documents/258457
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