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Two rhodamine-modified half-sandwich Ir(III) complexes with the general formula [(Cp x )Ir(ĈN) Cl] were synthesized and characterized, where Cp x is 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl (Cp xbiph ). Both complexes showed potent anticancer activity against A549, HeLa, and HepG2 cancer cells and normal cells, and altered ligands had an effect on proliferation resistance. The complex enters cells through energy dependence, and because of the different ligands, not only could it affect the anticancer ability of the complex but also could affect the degree of complex lysosome targeting, lysosomal damage, and further prove the antiproliferative mechanism of the complex. Excitingly, antimetastatic experiments demonstrated that complex 1 has the ability to block the migration of cancer cells. Furthermore, although the complex did not show a stronger ability to interfere with the coenzyme NAD + /NADH pair by transfer hydrogenation, the intracellular reactive oxygen species (ROS) content has shown a marked increase. NF-κB activity is increased by ROS regulation, and the role of ROS-NF-κB signaling pathway further induces apoptosis. Moreover, cell flow experiments also demonstrated that complex 1 blocked the cell cycle in S phase, but the complex did not cause significant changes in the mitochondrial membrane potential.

Theranostic Lysosomal Targeting Anticancer and Antimetastatic Agents: Half-Sandwich Iridium(III) Rhodamine Complexes