Analytica chimica acta · 2025
A novel NIR iridium(III) complex-based probe for accurate imaging of mitochondrial biothiols in ferroptosis-mediated lung ischemia-reperfusion injury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Jiang Lin, Liu Chaolong, Wang Wenyu, Li Feng, Ma Qingming, Sun Yong
Аннотация
BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a pathological condition characterized by aggravated oxidative-inflammatory tissue damage that occurs upon blood flow restoration after ischemia. LIRI can lead to severe complications, including primary graft dysfunction in lung transplants and multi-organ failure. However, current treatments remain limited. Studies indicate that ferroptosis exacerbates LIRI through mitochondrial biothiols dyshomeostasis. Visualizing mitochondrial biothiols during ferroptosis is crucial for understanding LIRI pathology and developing new therapies. Nevertheless, reliable imaging methods to track these biothiols in ferroptosis-mediated LIRI are still lacking.
RESULTS: In this study, we developed a biothiols-activated near-infrared (NIR) iridium(III) complex probe, termed NIR-Ir-BDS, for specifically and visually monitoring mitochondrial biothiols fluctuations in ferroptosis-mediated LIRI. NIR-Ir-BDS exhibits very weak NIR luminescence. Upon exposure to biothiols, the 2,4-dinitrobenzene sulfonamide (DBS) group of NIR-Ir-BDS undergoes rapid cleavage through a nucleophilic substitution reaction with the thiol group (-SH), yielding NIR-Ir-BH that exhibits intense NIR luminescence. The probe demonstrates a large Stokes shift, rapid response speed, excellent selectivity, high sensitivity, a satisfactory signal-to-noise ratio, good biocompatibility, and effective mitochondrial-targeting capability, enabling real-time monitoring of mitochondrial biothiols dynamics in living cells under pathological conditions. Furthermore, this study achieved, for the first time, the clear visualization of mitochondrial biothiols in mouse lung tissues during ferroptosis-mediated LIRI and systematically evaluated the in vivo therapeutic response to ferroptosis inhibition.
SIGNIFICANCE: These findings reveal a pivotal association between ferroptosis and the pathogenesis of LIRI, demonstrating that targeted pharmacological intervention in this pathway substantially mitigates disease progression. The newly developed probe NIR-Ir-BDS can be used as a reliable imaging tool to elucidate mitochondrial biothiol pathology in ferroptosis-mediated LIRI, thereby facilitating the development of innovative therapeutic interventions for this disease.
RESULTS: In this study, we developed a biothiols-activated near-infrared (NIR) iridium(III) complex probe, termed NIR-Ir-BDS, for specifically and visually monitoring mitochondrial biothiols fluctuations in ferroptosis-mediated LIRI. NIR-Ir-BDS exhibits very weak NIR luminescence. Upon exposure to biothiols, the 2,4-dinitrobenzene sulfonamide (DBS) group of NIR-Ir-BDS undergoes rapid cleavage through a nucleophilic substitution reaction with the thiol group (-SH), yielding NIR-Ir-BH that exhibits intense NIR luminescence. The probe demonstrates a large Stokes shift, rapid response speed, excellent selectivity, high sensitivity, a satisfactory signal-to-noise ratio, good biocompatibility, and effective mitochondrial-targeting capability, enabling real-time monitoring of mitochondrial biothiols dynamics in living cells under pathological conditions. Furthermore, this study achieved, for the first time, the clear visualization of mitochondrial biothiols in mouse lung tissues during ferroptosis-mediated LIRI and systematically evaluated the in vivo therapeutic response to ferroptosis inhibition.
SIGNIFICANCE: These findings reveal a pivotal association between ferroptosis and the pathogenesis of LIRI, demonstrating that targeted pharmacological intervention in this pathway substantially mitigates disease progression. The newly developed probe NIR-Ir-BDS can be used as a reliable imaging tool to elucidate mitochondrial biothiol pathology in ferroptosis-mediated LIRI, thereby facilitating the development of innovative therapeutic interventions for this disease.