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A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells
Author(s) -
Lameijer Lucien N.,
Ernst Daniël,
Hopkins Samantha L.,
Meijer Michael S.,
Askes Sven H. C.,
Le Dévédec Sylvia E.,
Bonnet Sylvestre
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201703890
Subject(s) - nicotinamide phosphoribosyltransferase , cytotoxicity , phototoxicity , ruthenium , chemistry , photodynamic therapy , cancer cell , cancer research , biophysics , cytotoxic t cell , microbiology and biotechnology , biochemistry , in vitro , cancer , biology , medicine , nad+ kinase , enzyme , organic chemistry , catalysis
We describe two water‐soluble ruthenium complexes, [ 1 ]Cl 2 and [ 2 ]Cl 2 , that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21 J cm −2 ) of red light in an oxygen‐independent manner. Using a specific NAMPT activity assay, up to an 18‐fold increase in inhibition potency was measured upon red‐light activation of [ 2 ]Cl 2 , while [ 1 ]Cl 2 was thermally unstable. For the first time, the dark and red‐light‐induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1 % O 2 ). In skin (A431) and lung (A549) cancer cells, a 3‐ to 4‐fold increase in cytotoxicity was found upon red‐light irradiation for [ 2 ]Cl 2 , whether the cells were cultured and irradiated with 1 % or 21 % O 2 . These results demonstrate the potential of photoactivated chemotherapy for hypoxic cancer cells, in which classical photodynamic therapy, which relies on oxygen activation, is poorly efficient.