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

In this paper, three new iridium(III) complexes: [Ir(piq)2(DFIPP)]PF6 (piq = deprotonated 1-phenylisoquinoline,
DFIPP = 3,4-difluoro-2-(1H-imidazo[4,5-f][1,10]phenenthrolin-2-yl)phenol, 3a), [Ir(bzq)2(DFIPP)]PF6 (bzq = deprotonated benzo[h]quinoline, 3b), and [Ir(ppy)2(DFIPP)]PF6 (ppy = deprotonated 1-phenylpyridine, 3c), were
synthesized and characterized. The complexes were found to be nontoxic
to tumor cells via 3-(4,5-dimethylthiazole-2-yl)-diphenyltetrazolium
bromide (MTT) assay. Surprisingly, its liposome-entrapped complexes
3alip, 3blip, and 3clip on B16 cells showed strong cytotoxicity (IC50 = 13.6 ± 2.8, 9.6 ± 1.1, and 18.9 ± 2.1 μM).
Entry of 3alip, 3blip, and 3clip into B16 cells decreases mitochondrial
membrane potential, regulates Bcl-2 family proteins, releases cytochrome
c, triggers caspase family cascade reaction, and induces apoptosis.
In addition, we also found that 3alip, 3blip, and 3clip triggered
ferroptosis and autophagy. In vivo studies demonstrated that 3blip
inhibited melanoma growth in C57 mice with a high inhibitory rate
of 83.95%, and no organic damage was found in C57 mice.