Bichromophoric anticancer drug: Targeting lysosome with rhodamine modified cyclometalated Iridium(III) complexes

Four bichromophoric cyclometalated iridium complexes were synthesized and fully characterized. Their anti proliferative capacity against A549, HepG2 cells and HeLa cells as well as two human normal cells was studied by MTT assay. Rhodamine B modified complexes 2 and 4 were not cytotoxic to A549 cells while both rhodamine 6 g modified complexes 1 and 3 showed greater cytotoxicity than cisplatin. In particular, the antiproliferative activity of complex 3 was about 4.6 times than that of cisplatin. Thus, complex 3 was used for stability and pH sensitivity studies. The results indicated that the complex not only had rich fluorescence properties under acidic conditions, but also showed good stability. Further, interaction of complex with bovine serum albumin (BSA) has been investigated by UV-vis, fluorescence, synchronous fluorescence spectroscopy. The complexes have a certain ability to bind the BSA. Interestingly, these complexes can catalyze the reaction of the coenzyme NADH to NAD(+), which is consistent with the apparent growth of ROS in cells. In addition, complex 3 can cause S phase arrest in the cell cycle, induce apoptosis, and affect mitochondria] membrane potential changes. Localization experiments of intracellular complexes by confocal microscopy suggested that these complexes enter cancer cells through energy dependence and specifically target the lysosomes, thus resulting in the damage of lysosomes.