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Fluorescent Probe for Imaging Nitroxyl in Liver Injury
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A Near-Infrared Fluorescent Probe for Imaging Nitroxyl Dynamics in Ferroptosis-Associated Drug-Induced Liver Injury
发布时间：2026-08-14 发布者： 浏览次数：1
Article| August 13, 2026
A Near-Infrared Fluorescent Probe for Imaging Nitroxyl Dynamics in Ferroptosis-Associated Drug-Induced Liver Injury
Xianzhu Luo § Qiuxin Huang § Tian SuJihong ShenZiqiang Wang * Yanlong Xing * Fabiao Yu *
Anal. Chem. (2026) https://doi.org/10.1021/acs.analchem.6c04503
AbstractAs a global health challenge, drug-induced liver injury (DILI) is an acute inflammatory disease closely linked to ferroptosis. Ferroptosis, characterized by iron-dependent lipid peroxidation, has been implicated in diverse pathological conditions, however, its precise molecular mechanism in liver injury remains to be fully elucidated. As a key active nitrogen species, the concentration fluctuation of nitroxyl (HNO) is closely correlated with ferroptosis. Nevertheless, in situ and real-time monitoring of endogenous HNO remains highly challenging owing to its transient lifespan and prominent reactivity. To address this issue, we constructed a near-infrared fluorescent probe specifically activated by HNO to delineate the intrinsic interplay between ferroptosis and DILI, thereby facilitating early diagnosis. This probe features a rapid response rate, extremely specificity, high sensitivity, and outstanding photostability, successfully achieving precise detection and imaging of both exogenous and endogenous HNO in vitro and in vivo. Crucially, real-time monitoring of the dynamic fluctuations of HNO levels with the probe explicitly unveiled a tight correlation of the ferroptosis process with DILI. Notably, inhibiting ferroptosis could significantly alleviate the progression of liver injury. Overall, this work not only provides a powerful molecular tool for the diagnosis of ferroptosis-associated liver diseases, but also offers important theoretical foundations and new strategies for the early clinical intervention of liver injury and related drug screening.
In summary, we have developed a novel NIR fluorescent probe (DCI-Cl-HNO) for precise monitoring of the dynamic levels of HNO during the DILI process. DCI-Cl-HNO exhibits efficient performance for HNO detection, including a rapid response, high specificity, and outstanding sensitivity. Furthermore, this probe demonstrates excellent performance in tracking fluctuations of both exogenous and endogenous HNO, and has been successfully applied to monitor the overproduction of HNO in an Erastin-induced cellular model of ferroptosis. We not only successfully achieved real-time tracking of fluctuations in endogenous and exogenous HNO levels in cells, but also clearly monitored the excessive production of HNO in Erastin-induced cellular model of ferroptosis. Crucially, with the help of this probe, we intensively investigated the correlation between ferroptosis and DILI in both cellular and murine models, confirming that the occurrence and development of DILI are accompanied by the pathological process of ferroptosis. Therefore, this work not only provides insights into the association between DILI and ferroptosis, but also offers a promising molecular imaging strategy for the diagnosis of DILI.
https://blog.sciencenet.cn/blog-2438823-1547863.html
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