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Mitochondria-targeting NIR fluorescent probe for rapid, highly sensitive and selective visualization of nitroxyl in live cells, tissues and mice
Science China Chemistry ( IF 10.4 ) Pub Date : 2019-10-21 , DOI: 10.1007/s11426-019-9604-3
Jianguo Wang , Wenping Zhu , Chunbin Li , Pengfei Zhang , Guoyu Jiang , Guangle Niu , Ben Zhong Tang

Nitroxyl (HNO) has been reported to possess unique biological and pharmacological performances, and emerged as a novel therapy for congestive heart failure. Recent studies also suggest that HNO may be produced and involved in important metabolisms in mitochondria. However, due to its high reactivity and short life properties, fast, sensitive and selective observation and monitoring of HNO related dynamic changes in mitochondria still remains a great challenge. Herein, we synthesized a mitochondria-targeting near-infrared (NIR) fluorescent probe (DCMHNO) for rapid detection of HNO with remarkably high sensitivity, selectivity and photostability. DCMHNO shows fast response (about 4 min) towards HNO via 2-(diphenylphosphino)benzoyl group through the Staudinger reaction to boost the bright NIR emission (700 nm) with excellent sensitivity (detection limit of 13 nM), high pH stability and very low interference from other species. DCMHNO can selectively locate in mitochondria and visualize exogenous and endogenous HNO in live HeLa cells with high biocompatibility and photostability. The probe could also monitor the interaction between NO and H2S that gives rise to the generation of HNO in live HeLa cells. In addition, DCMHNO was further utilized in ex vivo NIR imaging of HNO in live mouse liver tissues at the depth of about 50 µm. In vivo imaging of HNO with high signal-to-noise ratio in live mice was also realized by using DCMHNO. These remarkable imaging performances could render NIR DCMNHNO as a useful tool to reveal HNO related dynamic changes in live samples.

中文翻译:

靶向线粒体的NIR荧光探针可快速,高度灵敏和选择性地观察活细胞,组织和小鼠中的硝氧基

据报道,硝基氧(HNO)具有独特的生物学和药理学性能,并已成为充血性心力衰竭的一种新型疗法。最近的研究还表明,HNO可能在线粒体中产生并参与重要的代谢。然而,由于其高反应性和短寿命特性,线粒体中HNO相关动态变化的快速,灵敏和选择性的观察和监测仍然是一个巨大的挑战。本文中,我们合成了靶向线粒体的近红外(NIR)荧光探针(DCMHNO),用于快速检测HNO,具有极高的灵敏度,选择性和光稳定性。DCMHNO显示通过Staudinger反应通过2-(二苯基膦基)苯甲酰基对HNO的快速响应(约4分钟),从而以出色的灵敏度(检测限为13 nM),高pH稳定性和极低的灵敏度提高了明亮的近红外发射(700 nm)。来自其他物种的干扰。DCMHNO可以选择性地定位于线粒体中,并以高生物相容性和光稳定性显示活HeLa细胞中的外源性和内源性HNO。该探针还可以监测NO和H之间的相互作用2 S导致在活HeLa细胞中生成HNO。此外,DCMHNO还用于活体小鼠肝脏组织中HNO的离体NIR成像,深度约为50 µm。通过使用DCMHNO,还可以在活体小鼠中实现具有高信噪比的HNO的体内成像。这些出色的成像性能可以使NIR DCMNHNO成为揭示活样品中HNO相关动态变化的有用工具。
更新日期:2019-10-24
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