The formation of atherosclerotic plaques is the root cause of various cardiovascular diseases (CVDs). Effective CVD interventions thus call for precise identification of the plaques to aid clinical assessment and treatment of such diseases. In this study, we introduced a dual-analyte sequentially activated logic fluorescence reporting system CNN2-B to precisely identify the atherosclerotic plaques in vivo. This probe was achieved by creating a dual-locked fluorescent sensor that permits highly specific and sensitive detection of peroxynitrite and lipid droplets─the two hallmarks of atherosclerosis (AS). The recognition group of the probe removed after reacting with ONOO^– and intramolecular charge rearrangement occurred to generate a coumarin derivative structure. This structure had a strong solvent effect; it could recognize lipid droplets (LDs) in cells, thus exhibiting fluorescence without secondary molecular adjustment. The fluorescence was tremendously quenched by double locking; thus, an extreme fluorescence enhancement factor (F/F₀) ratio of 365 for CNN2-B was obtained. Importantly, CNN2-B could move from the mitochondria to lipid droplets after being activated. CNN2-B exhibited higher selectivity and signal-to-noise (S/N) ratio than commercial probe hydroxyphenyl fluorescein (HPF). Therefore, atherosclerotic plaques in mouse models were delineated clearly by fluorescence imaging after in situ administration of CNN2-B.

中文翻译：

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过氧亚硝酸盐/脂滴序列激活的双锁荧光探针可实现动脉粥样硬化斑块的精确术中成像

动脉粥样硬化斑块的形成是各种心血管疾病 (CVD) 的根本原因。因此，有效的 CVD 干预需要精确识别斑块，以帮助临床评估和治疗此类疾病。在这项研究中，我们引入了双分析物顺序激活逻辑荧光报告系统 CNN2-B，以精确识别体内动脉粥样硬化斑块。该探针是通过创建一个双锁荧光传感器实现的，该传感器可以高度特异性和灵敏地检测过氧亚硝酸盐和脂滴——动脉粥样硬化 (AS) 的两个标志。与ONOO反应后去除的探针识别基团^——并发生分子内电荷重排，生成香豆素衍生物结构。该结构具有很强的溶剂作用；它可以识别细胞中的脂滴 (LD)，从而无需二次分子调节即可显示荧光。双重锁定极大地淬灭了荧光；因此，获得了 CNN2-B 的 365 的极端荧光增强因子 ( F / F _{0 ) 比率。}重要的是，CNN2-B 在被激活后可以从线粒体移动到脂滴。CNN2-B 表现出比商用探针羟苯基荧光素 (HPF) 更高的选择性和信噪比 (S/N)。因此，小鼠模型中的动脉粥样硬化斑块在 原位后通过荧光成像清晰地描绘出来CNN2-B 的管理。