School of Engineering, China Pharmaceutical University, Nanjing 211198, China.
School of Mechanical Engineering, Southeast University, Nanjing 211189, China.
J Med Chem. 2024 Mar 14;67(5):4026-4035. doi: 10.1021/acs.jmedchem.3c02344. Epub 2024 Feb 15.
Rheumatoid arthritis (RA) is a destructive autoimmune disease, where nitric oxide (NO) is closely implicated in the inflammatory processes of RA. Therefore, direct visualization of NO is essential to assess the pathological changes in RA. Herein, a mitochondrial-targeted near-infrared ratiometric fluorescent probe (NFL-NH), based on the intramolecular charge transfer effect, was synthesized and applied to monitor the changes of NO content in early RA. Specially, probe NFL-NH showed a 44-fold fluorescent intensity ratio (/) response toward NO with a detection limit of 0.536 nM, enabling qualitative and quantitative analysis of NO. Additionally, NFL-NH can accurately target mitochondria and sensitively detect exogenous and endogenous NO in RAW 264.7 cells. Notably, RA monitoring assays demonstrated that NFL-NH can rapidly detect NO levels associated with the inflammatory damage degree in RA mice models by ratiometric fluorescence imaging. These results validate that NFL-NH holds significant potential for diagnosing NO-mediated RA diseases.
类风湿性关节炎(RA)是一种破坏性的自身免疫性疾病,其中一氧化氮(NO)与 RA 的炎症过程密切相关。因此,直接可视化 NO 对于评估 RA 的病理变化至关重要。在此,基于分子内电荷转移效应,合成了一种线粒体靶向近红外比率荧光探针(NFL-NH),并将其用于监测早期 RA 中 NO 含量的变化。特别地,探针 NFL-NH 对 NO 表现出 44 倍的荧光强度比(I/I)响应,检测限为 0.536 nM,能够对 NO 进行定性和定量分析。此外,NFL-NH 可以准确靶向线粒体,并在 RAW 264.7 细胞中灵敏地检测外源性和内源性 NO。值得注意的是,RA 监测实验表明,NFL-NH 可以通过比率荧光成像快速检测与 RA 小鼠模型中炎症损伤程度相关的 NO 水平。这些结果验证了 NFL-NH 具有诊断由 NO 介导的 RA 疾病的巨大潜力。