Evaluation\nof Efficiency of Liposome-Entrapped Iridium(III)\nComplexes Inhibiting Tumor Growth In Vitro and In Vivo

In this paper, three new iridium(III) complexes: [Ir(piq)<sub>2</sub>(DFIPP)]PF<sub>6</sub> (piq = deprotonated 1-phenylisoquinoline,\nDFIPP = 3,4-difluoro-2-(1<i>H</i>-imidazo[4,5-<i>f</i>][1,10]phenenthrolin-2-yl)phenol, <b>3a</b>), [Ir(bzq)<sub>2</sub>(DFIPP)]PF<sub>6</sub> (bzq = deprotonated benzo[<i>h</i>]quinoline, <b>3b</b>), and [Ir(ppy)<sub>2</sub>(DFIPP)]PF<sub>6</sub> (ppy = deprotonated 1-phenylpyridine, <b>3c</b>), were\nsynthesized and characterized. The complexes were found to be nontoxic\nto tumor cells via 3-(4,5-dimethylthiazole-2-yl)-diphenyltetrazolium\nbromide (MTT) assay. Surprisingly, its liposome-entrapped complexes\n3alip, 3blip, and 3clip on B16 cells showed strong cytotoxicity (IC<sub>50</sub> = 13.6 ± 2.8, 9.6 ± 1.1, and 18.9 ± 2.1 μM).\nEntry of 3alip, 3blip, and 3clip into B16 cells decreases mitochondrial\nmembrane potential, regulates Bcl-2 family proteins, releases cytochrome\nc, triggers caspase family cascade reaction, and induces apoptosis.\nIn addition, we also found that 3alip, 3blip, and 3clip triggered\nferroptosis and autophagy. In vivo studies demonstrated that 3blip\ninhibited melanoma growth in C57 mice with a high inhibitory rate\nof 83.95%, and no organic damage was found in C57 mice.