期刊
ANALYTICAL CHEMISTRY
卷 91, 期 7, 页码 4771-4779出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.9b00317
关键词
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资金
- National Key R&D Program of China [2017YFA0207303]
- National Science Fund for Distinguished Young Scholars [21725502]
- Key Basic Research Program of Science and Technology Commission of Shanghai Municipality [17JC1400100]
- China Post-doctoral Science Foundation [KLH1615151]
- International Scientific Partnership Program ISPP at King Saud University [0100]
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.
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