Isomeric Ir(iii) complexes for tracking mitochondrial pH fluctuations and inducing mitochondrial dysfunction during photodynamic therapy.
DALTON TRANSACTIONS(2019)
摘要
Mitochondrial pH is known to be alkaline (near 8.0) and has emerged as a potential factor for mitochondrial function and disorder. Here we investigate two pairs of isomeric phosphorescent Ir(iii) complexes (1-4) that show mitochondrial pH-responsive properties and induce mitochondrial dysfunction during photodynamic therapy. These complexes are designed to function by controlling the protonation of the benzimidazole and carboxyl groups. 1 and 2 exhibit enhanced emission intensity and a blue-shift emission change in response to pH alterations from 6.0 to 8.0. They have ideal pK(a) values (7.49 for 1 and 7.41 for 2) and show mitochondria-specific phosphorescence staining in situ, thereby allowing the monitoring of mitochondrial pH in live cells. 3 and 4 produce abundant intracellular ROS and exhibit high phototoxicities against cancer cells. Interestingly, these pH-responsive probes can be utilized to monitor the change in mitochondrial pH and mitochondrial damage during photodynamic therapy (PDT), which provides a convenient method for the in situ monitoring of therapeutic effects and the assessment of treatment outcomes.
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关键词
mitochondrial dysfunction
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