Innocent But Deadly: Nontoxic Organoiridium Catalysts Promote Selective Cancer Cell Death

We demonstrate that nontoxic organoiridum complexes can selectively chemosensitize cancer cells toward platinum antiproliferative agents. Treatment of human cancer cells (breast, colon, eye/retina, head/neck, lung, ovary, and blood) with the iridium chemosensitizers led to lowering of the 50 % growth inhibition concentration (IC₅₀ ) of the Pt drug carboplatin by up to ∼30-50 %. Interestingly, non-cancer cells were mostly resistant to the chemosensitizing effects of the iridium complexes. Cell culture studies indicate that cancer cells that were administered with Ir show significantly higher reactive oxygen species concentrations as well as NAD⁺ /NADH ratios (oxidized vs. reduced nicotinamide adenine dinucleotide) than Ir-treated non-cancer cells. These biochemical changes are consistent with a catalytic transfer hydrogenation cycle involving the formation of iridium-hydride species from the reaction of the iridium catalysts with NADH and subsequent oxidation in air to generate hydrogen peroxide.