Liposomes capable of generating photons of blue light in situ by triplet-triplet annihilation upconversion of either green or red light, were prepared. The red-to-blue upconverting liposomes were capable of triggering the photodissociation of ruthenium polypyridyl complexes from PEGylated liposomes using a clinical grade photodynamic therapy laser source (630 nm).
We describe two water‐soluble ruthenium complexes, [1]Cl2 and [2]Cl2, 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]Cl2, while [1]Cl2 was thermally unstable. For the first time, the dark and red‐light‐induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1 % O2). In skin (A431) and lung (A549) cancer cells, a 3‐ to 4‐fold increase in cytotoxicity was found upon red‐light irradiation for [2]Cl2, whether the cells were cultured and irradiated with 1 % or 21 % O2. 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.
A LED-based cell irradiation system was built that can irradiate a 96-well plate with monochromatic light at controlled temperature and with a built-in dark control. This system was used to study the response of six human cancer cell lines to blue, green, and red light.
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