Cyclometalated Ir(III) Complexes as Lysosome-Targeted Photodynamic Anticancer Agents

Abstract

We have designed and synthesized two Ir(III) complexes ( Ir1 and Ir2 ) coordinated with an 8-sulfonamidoquinoline derivative ligand as photosensitizers, which exhibit strong red phosphorescence emission and a long phosphorescence lifetime. The Ir(III) complexes exhibit a high population of triplet states, which enable red phosphorescence and efficient singlet oxygen generation. Ir1 and Ir2 rapidly enter the cancer cells and accumulate in lysosomes, producing large amounts of intracellular singlet oxygen when exposed to light irradiation, eventually leading to cancer cell death, and the phototoxic indexes of complexes Ir1 and Ir2 against cancer cells are in the range of 76–228. Overall, our studies indicate that the synthesized Ir(III) complexes with quinoline ligands exhibit photosensitizing properties, effectively inducing cancer cell death when exposed to light. These promising results suggest their potential application in photodynamic therapy.

Tuning the Organelle-Specific Imaging and Photodynamic Therapeutic Efficacy of Theranostic Mono- and Trinuclear Organometallic Iridium(III) Complexes

“…Given that all the complexes except for IrB3 exhibited low cell cytotoxicity (IC 50 values of 36.59, 46.44, 32.69, 51.09) at 12 h post-incubation, we further increased the incubation time up to 24 h. The IC 50 values after an extended period of incubation of cells with the test compounds were greatly increased, resulting in a higher phototherapeutic index (PI) (IC 50 dark: IC 50 light, in a range of 30–260). Our result is in line with previous publications where the PI indices (IC 50 dark: IC 50 light) of Ir­(III)­complexes are in the range of 76–228 or, however, in different cell lines . A similar observation was also recorded where the PI indexes were within 7–14 in human A549 cells photoirradiated with a light source of 405 nm .…”

“…Our result is in line with previous publications where the PI indices (IC 50 dark: IC 50 light) of Ir(III)complexes are in the range of 76−228 or, however, in different cell lines. 20 A similar observation was also recorded where the PI indexes were within 7−14 in human A549 cells photoirradiated with a light source of 405 nm. 21 Nevertheless, we provide evidence that the IrB3 complexes can have a strong cytotoxic effect on the MCF7 cells under photoirradiation, followed by IrA2, IrB2, and IrA3 (Table 3).…”