In Vitro and In Vivo Antitumor Assay of Mitochondrially Targeted Fluorescent Half-Sandwich Iridium(III) Pyridine Complexes

Half-sandwich iridium(III) complexes show potential value in the anticancer field. However, complexes with favorable luminescence performance are rare, which limits further investigation of the anticancer mechanism. In this paper, 10 triphenylamine-modified fluorescent half -sandwich iridium(III) pyridine complexes {[(eta 5-Cpx)Ir(L)Cl2]} (Ir1- Ir10) were prepared and showed potential antiproliferative activity, effectively inhibiting the migration of A549 cells. Ir6, showing the best activity among these complexes, exhibited excellent fluorescence perform-ance (absolute fluorescence quantum yield of 15.17%) in solution. Laser confocal detection showed that Ir6 followed an energy-dependent cellular uptake mechanism, specifically accumulating in mitochondria (Pearson co-localization coefficient of 0.95). A Western blot assay further confirmed the existence of a mitochondrial apoptotic channel. Additionally, Ir6 could arrest the cell cycle at the G2/M phase, catalyze NADH oxidation, reduce the mitochondrial membrane potential, induce an increase in the level of intracellular reactive oxygen species, and exhibit a mechanism of oxidation. An in vivo antitumor assay confirmed that Ir6 can effectively inhibit tumor growth and is safer than cisplatin.

Automated summary

This paper investigates the potential value of half-sandwich iridium(III) complexes with favorable luminescence performance in the anticancer field. Ten fluorescent complexes were prepared and showed potential antiproliferative activity, with Ir6 exhibiting the best activity and excellent fluorescence performance. Ir6 followed an energy-dependent cellular uptake mechanism, specifically accumulating in mitochondria and inducing mitochondrial-mediated apoptosis. It also arrested the cell cycle, catalyzed NADH oxidation, reduced the mitochondrial membrane potential, induced an increase in ROS level, and exhibited an oxidation mechanism. In vivo antitumor assay confirmed that Ir6 effectively inhibited tumor growth and was safer than cisplatin.