Targeted photoredox catalysis in cancer cells

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

Research output: Contribution to journalArticle

2 Downloads (Pure)

Abstract

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]PF 6 ([1]PF 6, 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.

Original languageEnglish
Pages (from-to)1041-1048
Number of pages8
JournalNature Chemistry
Volume11
DOIs
Publication statusPublished - 23 Sep 2019

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Huang, H., Banerjee, S., Qiu, K., Zhang, P., Blacque, O., Malcomson, T., Paterson, M. J., Clarkson, G. J., Staniforth, M., Stavros, V. G., Gasser, G., Chao, H., & Sadler, P. J. (2019). Targeted photoredox catalysis in cancer cells. Nature Chemistry, 11, 1041-1048. https://doi.org/10.1038/s41557-019-0328-4