Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy.
Fang-Xin WangMu-He ChenYan-Nan LinHang ZhangCai-Ping TanLiang-Nian JiZong-Wan MaoPublished in: ACS applied materials & interfaces (2017)
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-2), 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.
Keyphrases
- photodynamic therapy
- cell migration
- fluorescence imaging
- reactive oxygen species
- oxidative stress
- cell death
- protein kinase
- fluorescent probe
- endothelial cells
- living cells
- high throughput
- cell cycle arrest
- type diabetes
- vascular endothelial growth factor
- blood pressure
- molecular dynamics
- birth weight
- single molecule
- skeletal muscle
- ionic liquid
- resistance training
- high fat diet induced
- signaling pathway
- weight gain
- induced apoptosis
- high intensity
- wild type