TY - JOUR
T1 - Photoactivated Osmium Arene Anticancer Complexes
AU - Xue, Xuling
AU - Fu, Ying
AU - He, Liang
AU - Salassa, Luca
AU - He, Ling-Feng
AU - Hao, Yuan-Yuan
AU - Koh, Madeleine J.
AU - Soulié, Clément
AU - Needham, Russell J.
AU - Habtemariam, Abraha
AU - Garino, Claudio
AU - Lomachenko, Kirill A.
AU - Su, Zhi
AU - Qian, Yong
AU - Paterson, Martin J.
AU - Mao, Zong-Wan
AU - Liu, Hong-Ke
AU - Sadler, Peter J.
N1 - Funding Information:
We thank Dr. Zhe Liu, Dr. Yao Zhao, and Dr. Lihong Li for their help with NMR and MS experiments and Dr. P. Glatzel, Dr. E. Gallo, Dr. D. Gianolio, and Prof. C. Lamberti for the assistance during the XAS experiment at ID26 beamline of the ESRF. We thank NSFC (nos. 22077066, 21771109, 21778033, 21701195, 21837006, and 21977052), NSF of Jiangsu Province (no. BK20171472), ERC (grant 247450), EPSRC (grants EP/F034210/1, EP/P030572/1, EP/P001459, and EP/T021675), Anglo American Platinum, and the Severo Ochoa Centres of Excellence Programme for L.S. by the Spanish State Research Agency (ref CEX2018-000867-S) for their financial support.
Publisher Copyright:
©
PY - 2021/12/6
Y1 - 2021/12/6
N2 - Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2′-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 μM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).
AB - Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2′-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 μM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).
UR - http://www.scopus.com/inward/record.url?scp=85115662576&partnerID=8YFLogxK
U2 - 10.1021/acs.inorgchem.1c00241
DO - 10.1021/acs.inorgchem.1c00241
M3 - Article
C2 - 34503331
SN - 0020-1669
VL - 60
SP - 17450
EP - 17461
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 23
ER -