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

作者：Dandan Li, Shangfeng Wang, Zuhai Lei, Caixia Sun, Ahmed Mohamed El‐Toni, Mansour Saleh Alhoshan, Yong Fan, Fan Zhang · 发表于：Analytical Chemistry · 年份：2019 · DOI：10.1021/acs.analchem.9b00317 · 被引用次数：190 · 研究领域：Nanoplatforms for cancer theranostics、Molecular Sensors and Ion Detection、Sulfur Compounds in Biology

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.