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

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.