Peroxynitrite Activatable NIR-II Fluorescent Molecular Probe for Drug-Induced Hepatotoxicity Monitoring

Drug-induced hepatotoxicity represents an important challenge for safety in drug development. The production of peroxynitrite (ONOO–) is proposed as an early sign in the progression of drug-induced hepatotoxicity. Currently, reported ONOO– probes mainly emit in the visible range or the first NIR win...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2019-04, Vol.91 (7), p.4771-4779
Main Authors: Li, Dandan, Wang, Shangfeng, Lei, Zuhai, Sun, Caixia, El-Toni, Ahmed Mohamed, Alhoshan, Mansour Saleh, Fan, Yong, Zhang, Fan
Format: Article
Language:English
Subjects:
Acetylcysteine
Analytical chemistry
Biosensors
Chemistry
Drug development
Fluorescence
Hepatotoxicity
In vivo methods and tests
Infrared windows
Monitoring
Penetration depth
Peroxynitrite
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Summary:Drug-induced hepatotoxicity represents an important challenge for safety in drug development. The production of peroxynitrite (ONOO–) is proposed as an early sign in the progression of drug-induced hepatotoxicity. Currently, reported ONOO– probes mainly emit in the visible range or the first NIR window, which have limited in vivo biosensing application due to the autofluorescence and photon scattering. Herein, we developed a peroxynitrite activatable second near-infrared window (NIR-II) molecular probe for drug-induced hepatotoxicity monitoring, based on the fusion of an NIR-II fluorescence turn-on benzothiopyrylium cyanines skeleton and the phenyl borate. In the presence of ONOO–, the probe IRBTP-B can turn on its NIR-II fluorescence by yielding its fluorophore IRBTP-O and display good linear response to ONOO–. Tissue phantom study confirmed reliable activated signals could be acquired at a penetration depth up to 5 mm. Using this probe, we disclose the upregulation of ONOO– in a preclinical drug-induced liver injury model and the remediation with N-acetyl cysteine (NAC) in vivo. We expect that this strategy will serve as a general method for the development of an activatable NIR-II probe based on the hydroxyl functionalized reactive sites by analyte-specific triggering.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.9b00317