Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy

Abstract

Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can effectively inhibit several cancerous processes, including cell migration, invasion, colony formation, and angiogenesis. Interestingly, they show a much higher singlet oxygen quantum yield in an acidic solution than in a neutral solution. Upon irradiation at 425 nm with low energy (1.2 J cm), they can induce apoptosis through lysosomal damage, evaluation of reactive oxygen species level, and activation of caspase-3/7. The highest phototoxicity index is >476, with almost no dark cytotoxicity observed for Ir4. Ir4 can also inhibit tumor growth effectively in nude mice in vivo after photodynamic therapy. An in vitro assay against 70 kinases indicates that maternal embryonic leucine zipper kinase (MELK), PIK3CA, and AMPK are the possible molecular targets. The half maximal inhibitory concentration of Ir4 toward MELK is 1.27 μM. Our study demonstrates that these Ir(III) complexes are promising anticancer agents with dual functions, including metastasis inhibition and lysosome-damaged photodynamic therapy.

Half‐sandwich Ruthenium (II) complexes with triphenylamine modified dipyridine skeleton and application in biology/luminescence imaging

“…The diffusion of cancer cells is closely related to cell migration, which is significative for studying the effect of complexes on cancer cell antimigration . The effects of complexes 2 and 4 on A549 antimigration were investigated by wound healing migration assays.…”

Recent Advances in the Design of Targeted Iridium(III) Photosensitizers for Photodynamic Therapy

“…Based on these findings, they developed a further series of Ir III complexes ( 66 – 69 , Scheme ) containing benzimidazole groups for lysosome‐targeted PDT . These complexes showed much higher singlet‐oxygen quantum yields in acidic solution (pH 5.4) than in neutral solution.…”

“…The highest PI achieved was >476 for 69 in HeLa cells, with almost no dark toxicity. Complex 69 can also inhibit tumor growth effectively in nude mice in vivo after photodynamic therapy . An in vitro assay against 70 kinases indicated that maternal embryonic leucine zipper kinase (MELK), phosphoinositide‐3‐kinase regulatory subunit 1 (PIK3CA/PIK3R1 (p110 α/p85 α)), and AMP‐activated protein kinase (AMPK A2/B1/G1) were among the most likely three possible molecular targets.…”

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

“…76,77 In last years, the preclinical toxicity of variety of metal complexes (Ag, Au, Ir, Os, Pt, Ru, etc.) has been tested in the zebrafish embryos, [78][79][80][81] while, to the best of our knowledge, only one study explored Re(I) tricarbonyl complexes in this model. 51 Herein, according to the determined LC50 values ( were compared to those in the control (DMSO-treated) group and the groups treated with clinically approved drugs -cisplatin, doxorubicin and sunitinib-malate.…”