State Key Laboratory of Medicinal Chemical Biology, Research Center for Analytical Sciences, Tianjin Key Laboratory of Molecular Recognition and Biosensing, and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Angew Chem Int Ed Engl. 2022 Jul 18;61(29):e202204518. doi: 10.1002/anie.202204518. Epub 2022 May 3.
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, diagnosis, and treatment of such diseases. In this study, we introduce a dual-target sequentially activated fluorescence reporting system, termed in-sequence high-specificity dual-reporter unlocking (iSHERLOCK), to precisely identify the atherosclerotic plaques in vivo and ex vivo. ISHERLOCK was achieved by creating a three-in-one fluorescent probe that permits highly specific and sensitive detection of lipid droplets and hypochlorous acid via "off-on" and ratiometric readouts, respectively. Based on this format, the upregulated lipid accumulation and oxidative stress-the two hallmarks of atherosclerosis (AS)-were specifically measured in the atherosclerotic plaques, breaking through the barrier of precise tissue biopsy of AS and thus aiding effective CVD stewardship.
动脉粥样硬化斑块的形成是各种心血管疾病（CVDs）的根本原因。因此，有效的 CVD 干预措施需要精确识别斑块，以辅助此类疾病的临床评估、诊断和治疗。在这项研究中，我们引入了一种双靶顺序激活荧光报告系统，称为顺序高特异性双报告解锁（iSHERLOCK），以在体内和体外精确识别动脉粥样硬化斑块。iSHERLOCK 通过创建一个三合一荧光探针来实现，该探针分别通过“开-关”和比率读数，允许对脂滴和次氯酸的高度特异性和灵敏检测。基于这种格式，动脉粥样硬化（AS）的两个标志——上调的脂质积累和氧化应激——在动脉粥样硬化斑块中被特异性地测量，突破了 AS 精确组织活检的障碍，从而有助于有效的 CVD 管理。
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