<p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, whose pathogenesis is closely associated with oxidative stress. As a key biomarker of oxidative stress, peroxynitrite (ONOO<sup>−</sup>) plays a critical role in the onset and progression of AD. Consequently, developing efficient tools for ONOO<sup>−</sup> detection is crucial for the early diagnosis and pathological investigation of AD. In this study, we designed and synthesized a novel near-infrared (NIR) fluorescent probe, termed <b>CNOP</b>, for the specific recognition and detection of ONOO<sup>−</sup>. The probe demonstrated excellent optical responses to ONOO<sup>−</sup>, including high selectivity, outstanding sensitivity (with a detection limit in the nmol/L range), a large Stokes shift, and notably, a significant NIR fluorescence enhancement exceeding 300-fold. Leveraging these superior analytical properties, we successfully applied <b>CNOP</b> for the NIR fluorescence imaging of ONOO<sup>−</sup> in both live cells and the brains of AD model mice. The imaging results clearly revealed a markedly elevated level of ONOO<sup>−</sup> in the AD model mice brain compared to that of the wild-type control group, highlighting the probe’s considerable potential for application in AD pathological research.</p>

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A Highly Sensitive Near-infrared Organic Fluorescent Probe for Peroxynitrite Imaging in Alzheimer’s Disease Model Mouse Brain

  • Wenjing Zhang,
  • Yujie Han,
  • Chenming Chan,
  • Qi-Wei Zhang

摘要

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, whose pathogenesis is closely associated with oxidative stress. As a key biomarker of oxidative stress, peroxynitrite (ONOO) plays a critical role in the onset and progression of AD. Consequently, developing efficient tools for ONOO detection is crucial for the early diagnosis and pathological investigation of AD. In this study, we designed and synthesized a novel near-infrared (NIR) fluorescent probe, termed CNOP, for the specific recognition and detection of ONOO. The probe demonstrated excellent optical responses to ONOO, including high selectivity, outstanding sensitivity (with a detection limit in the nmol/L range), a large Stokes shift, and notably, a significant NIR fluorescence enhancement exceeding 300-fold. Leveraging these superior analytical properties, we successfully applied CNOP for the NIR fluorescence imaging of ONOO in both live cells and the brains of AD model mice. The imaging results clearly revealed a markedly elevated level of ONOO in the AD model mice brain compared to that of the wild-type control group, highlighting the probe’s considerable potential for application in AD pathological research.