Targeted photoredox catalysis in cancer cells

被引：378

作者：

Huang, Huaiyi ^{[1
,2
]}

Banerjee, Samya ^{[2
]}

Qiu, Kangqiang ^{[3
]}

Zhang, Pingyu ^{[4
]}

Blacque, Olivier ^{[5
]}

Malcomson, Thomas ^{[6
]}

Paterson, Martin J. ^{[6
]}

Clarkson, Guy J. ^{[2
]}

Staniforth, Michael ^{[2
,7
]}

Stavros, Vasilios G. ^{[2
,7
]}

Gasser, Gilles ^{[8
]}

Chao, Hui ^{[3
]}

Sadler, Peter J. ^{[2
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Guangzhou, Guangdong, Peoples R China

[2] Univ Warwick, Dept Chem, Coventry, W Midlands, England

[3] Sun Yat Sen Univ, Sch Chem, MOE Key Lab Bioinorgan & Synthet Chem, Guangzhou, Guangdong, Peoples R China

[4] Shenzhen Univ, Coll Chem & Environm Engn, Shenzhen, Peoples R China

[5] Univ Zurich, Dept Chem, Zurich, Switzerland

[6] Heriot Watt Univ, Sch Engn & Phys Sci, Edinburgh, Midlothian, Scotland

[7] Univ Warwick, Dept Phys, Coventry, W Midlands, England

[8] PSL Univ, Chim ParisTech, Inst Chem Hlth & Life Sci, CNRS,Lab Inorgan Chem Biol, Paris, France

来源：

NATURE CHEMISTRY | 2019年 / 11卷 / 11期

基金：

英国工程与自然科学研究理事会; 美国国家科学基金会;

关键词：

PHOTODYNAMIC THERAPY; POLYPYRIDYL COMPLEXES; OXIDATIVE STRESS; REACTIVE OXYGEN; METAL-COMPLEXES; ACTIVATION; DEATH; NADH; PHOTOSENSITIZERS; APOPTOSIS;

D O I：

10.1038/s41557-019-0328-4

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：1041 / +

页数：15

共 58 条

[1] The activation of the c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling pathways protects HeLa cells from apoptosis following photodynamic therapy with hypericin [J].