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Targeted photoredox catalysis in cancer cells

Research output: Contribution to journalJournal articlepeer-review

  • Huaiyi Huang
  • Samya Banerjee
  • Kangqiang Qiu
  • Pingyu Zhang
  • Olivier Blacque
  • Thomas Malcomson
  • Martin J. Paterson
  • Guy J. Clarkson
  • Michael Staniforth
  • Vasilios G. Stavros
  • Gilles Gasser
  • Hui Chao
  • Peter J. Sadler
<mark>Journal publication date</mark>1/11/2019
<mark>Journal</mark>Nature Chemistry
Issue number11
Number of pages8
Pages (from-to)1041-1048
Publication StatusPublished
Early online date23/09/19
<mark>Original language</mark>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.