Anticancer Agent with Inexplicable Potency in Extreme Hypoxia: Characterizing a Light-Triggered Ruthenium Ubertoxin

被引：60

作者：

Cole, Houston D. ^{[1
]}

Roque, John A. ^{[1
,2
,3
]}

Shi, Ge ^{[1
]}

Lifshits, Liubov M. ^{[1
,3
]}

Ramasamy, Elamparuthi ^{[1
]}

Barrett, Patrick C. ^{[2
,4
]}

Hodges, Rachel O. ^{[2
,5
]}

Cameron, Colin G. ^{[1
]}

McFarland, Sherri A. ^{[1
]}

机构：

[1] Univ Texas Arlington, Dept Chem & Biochem, Arlington, TX 76019 USA

[2] Univ North Carolina Greensboro, Dept Chem & Biochem, Greensboro, NC 27402 USA

[3] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[4] Virginia Polytech Inst & State Univ, Carilion Sch Med, Roanoke, VA 24016 USA

[5] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2022年 / 144卷 / 22期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

ALPHA-OLIGOTHIOPHENES; PHOTODYNAMIC THERAPY; RU(II) COMPLEXES; PHOTOSENSITIZER; SENSITIZATION; LIGANDS; SINGLET;

D O I：

10.1021/jacs.1c09010

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Tumor hypoxia renders treatments ineffective that are directly (e.g., radiotherapy and photodynamic therapy) or indirectly (e.g., chemotherapy) dependent on tumor oxygenation. This study introduces a ruthenium compound as a light-responsive anticancer agent that is water-soluble, has minimal dark cytotoxicity, is active at concentrations as low as 170 pM in similar to 18.5% O-2 normoxia and near 10 nM in 1% O-2 hypoxia, and exhibits phototherapeutic indices as large as >500,000 in normoxia and >5,800 in 1% O-2 hypoxia using broadband visible and monochromatic blue light treatments. These are the largest values reported to date for any compound class. We highlight the response in four different cell lines to improve rigor and reproducibility in the identification of promising clinical candidates.

引用

页码：9543 / 9547

页数：5

共 34 条

[1] Marked Improvement in Photoinduced Cell Death by a New Tris-heteroleptic Complex with Dual Action: Singlet Oxygen Sensitization and Ligand Dissociation [J].

Albani, Bryan A. ;

Pena, Bruno ;

Leed, Nicholas A. ;

de Paula, Nataly A. B. G. ;

Pavani, Christiane ;

Baptista, Mauricio S. ;

Dunbar, Kim R. ;

Turro, Claudia .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2014, 136 (49) :17095-17101

[2] Selective Photoinduced Ligand Exchange in a New Tris-Heteroleptic Ru(II) Complex [J].

Albani, Bryan A. ;

Durr, Christopher B. ;

Turro, Claudia .

JOURNAL OF PHYSICAL CHEMISTRY A, 2013, 117 (50) :13885-13892

[3] Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future [J].

Alzeibak, Razan ;

Mishchenko, Tatiana A. ;

Shilyagina, Natalia Y. ;

Balalaeva, Irina V. ;

Vedunova, Maria V. ;

Krysko, Dmitri V. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (01)

[4] Phototoxicity of strained Ru(II) complexes: is it the metal complex or the dissociating ligand? [J].

Azar, Daniel F. ;

Audi, Hassib ;

Farhat, Stephanie ;

El-Sibai, Mirvat ;

Abi-Habib, Ralph J. ;

Khnayzer, Rony S. .

DALTON TRANSACTIONS, 2017, 46 (35) :11529-11532

[5] Yellow-light sensitization of a ligand photosubstitution reaction in a ruthenium polypyridyl complex covalently bound to a rhodamine dye [J].

Bahreman, Azadeh ;

Cuello-Garibo, Jordi-Amat ;

Bonnet, Sylvestre .

DALTON TRANSACTIONS, 2014, 43 (11) :4494-4505

[6] Comprehensive evaluation of the absorption, photophysical, energy transfer, structural, and theoretical properties of alpha-oligothiophenes with one to seven rings [J].

Becker, RS ;

deMelo, JS ;

Macanita, AL ;

Elisei, F .

JOURNAL OF PHYSICAL CHEMISTRY, 1996, 100 (48) :18683-18695

[7] Why develop photoactivated chemotherapy? [J].

Bonnet, Sylvestre .

DALTON TRANSACTIONS, 2018, 47 (31) :10330-10343

[8] Fine-Feature Modifications to Strained Ruthenium Complexes Radically Alter Their Hypoxic Anticancer Activity† [J].

Cole, Houston D. ;

Roque, John A., III ;

Lifshits, Liubov M. ;

Hodges, Rachel ;

Barrett, Patrick C. ;

Havrylyuk, Dmytro ;

Heidary, David ;

Ramasamy, Elamparuthi ;

Cameron, Colin G. ;

Glazer, Edith C. ;

McFarland, Sherri A. .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2022, 98 (01) :73-84

[9] To cage or to be caged? The cytotoxic species in ruthenium-based photoactivated chemotherapy is not always the metal [J].

Cuello-Garibo, Jordi-Amat ;

Meijer, Michael S. ;

Bonnet, Sylvestre .

CHEMICAL COMMUNICATIONS, 2017, 53 (50) :6768-6771

[10] Singlet and triplet energies of α-oligothiophenes:: A spectroscopic, theoretical, and photoacoustic study:: Extrapolation to polythiophene [J].

de Melo, JS ;

Silva, LM ;

Arnaut, LG ;

Becker, RS .

JOURNAL OF CHEMICAL PHYSICS, 1999, 111 (12) :5427-5433

← 1 2 3 4 →