Huang HSchool of Pharmaceutical Science (Shenzhen), Sun Yat-sen University, Guangzhou, China.
Banerjee SDepartment of Chemistry, University of Warwick, Coventry, UK.
Qiu KMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China.
Zhang PCollege of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China.
Blacque ODepartment of Chemistry, University of Zurich, Zurich, Switzerland.
Malcomson TSchool of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
Paterson MJSchool of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
Clarkson GJDepartment of Chemistry, University of Warwick, Coventry, UK.
Staniforth MDepartment of Chemistry, University of Warwick, Coventry, UK.
Stavros VGDepartment of Chemistry, University of Warwick, Coventry, UK.
Gasser GChimie 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 HMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China. ceschh@mail.sysu.edu.cn.
Sadler PJDepartment of Chemistry, University of Warwick, Coventry, UK. p.j.sadler@warwick.ac.uk.
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.