Atherosclerosis (AS) is a common disease associated with cholesterol metabolism. Cholesterol esterase (CHE), which is found primarily in the liver, intestines, adipose tissue, and skin, plays a crucial role in cholesterol metabolism; thus, it is a potential biomarker for the early diagnosis and therapeutic monitoring of AS. Traditional fluorescent probes for detecting AS often rely on general biomarkers such as reactive oxygen species (ROS) or proteases, which lack specificity. To address this limitation, we developed a novel CHE-responsive fluorescent probe, NR-CHE, which utilizes cholic acid as the recognition group. This probe was synthesized by an esterification reaction between cholic acid and a lipid droplet-targeting near-infrared dye, NR-OH. The NR-CHE probe integrated the lipid droplet-targeting capability of NR with the specific response of CHE, thus offering a unique affinity for cells with lipid abnormalities and enabling precise imaging of atherosclerosis. In vitro experiments demonstrated that NR-CHE exhibited superior optical properties, with a detection limit of 0.076 U/mL. Tests involving 32 common biological interferents confirmed that the recognition group cholic acid provided high selectivity to the probe. Cell experiments further validated that NR-CHE is an effective tool for monitoring endogenous CHE in live cells. Comprehensive fluorescence imaging assessments in an AS mouse model showed that NR-CHE delivered exceptional imaging accuracy. As an extended application, NR-CHE also demonstrated potential in image-guided surgical resection in a liver cancer model. Collectively, NR-CHE holds great promise as a tool for the accurate diagnosis of AS and for guiding tumor resection surgery.

中文翻译：

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胆固醇酯酶响应性近红外荧光探针，用于动脉粥样硬化的精确成像


动脉粥样硬化 （AS） 是一种与胆固醇代谢相关的常见疾病。胆固醇酯酶 （CHE） 主要存在于肝脏、肠道、脂肪组织和皮肤中，在胆固醇代谢中起着至关重要的作用;因此，它是 AS 早期诊断和治疗监测的潜在生物标志物。用于检测 AS 的传统荧光探针通常依赖于通用生物标志物，例如活性氧 （ROS） 或蛋白酶，这些生物标志物缺乏特异性。为了解决这一限制，我们开发了一种新型 CHE 响应性荧光探针 NR-CHE，它利用胆酸作为识别组。该探针是通过胆酸与脂质液滴靶向近红外染料 NR-OH 之间的酯化反应合成的。NR-CHE 探针将 NR 的脂滴靶向能力与 CHE 的特异性反应相结合，从而为脂质异常的细胞提供独特的亲和力，并实现动脉粥样硬化的精确成像。体外实验表明，NR-CHE 表现出优异的光学特性，检出限为 0.076U/mL。涉及 32 种常见生物干扰物的测试证实，识别组胆酸为探针提供了高选择性。细胞实验进一步验证了 NR-CHE 是监测活细胞中内源性 CHE 的有效工具。AS 小鼠模型中的全面荧光成像评估表明，NR-CHE 提供了卓越的成像准确性。作为一种扩展应用，NR-CHE 还在肝癌模型中的影像引导手术切除中显示出潜力。总的来说，NR-CHE 作为准确诊断 AS 和指导肿瘤切除手术的工具具有很大的前景。