Wu Kefeng, Yao Chi, Yang Dayong, Liu Dingbin
Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China; State Key Laboratory of Medicinal Chemical Biology, Research Center for Analytical Sciences, And Tianjin Key Laboratory of Molecular Recognition and Biosensing, College of Chemistry, Nankai University, Tianjin, 300071, China.
Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China.
Biosens Bioelectron. 2022 Aug 1;209:114273. doi: 10.1016/j.bios.2022.114273. Epub 2022 Apr 11.
Atherosclerosis (AS) is the primary cause of cardiovascular disorders, which lead to one-third of all death globally. However, the atherosclerosis process remains elusive due to the lack of appropriate analytical methods. Herein, we present the first nanoflare-based DNA sensor that could report the distribution of ClO (a typical marker of AS) in the atherosclerotic plaques. ClO-responsive phosphorothioate (PS) was inserted into DNA, which was then assembled with a gold nanoparticle (AuNP) core to form a ClO-specific nanoflare probe. The hydrolysis between PS and ClO triggered fluorescence turn-on of the probes, showing excellent sensitivity (as low as 8.51 nM) and specificity for ClO detection. In addition, the nanoflare probes exhibit superior performance in tracing the variations of endogenous and exogenous ClO in living RAW264.7 cells. After intravenous injection, the efficient accumulation of probes and fluorescence signal enhancement were observed in the atherosclerotic plaques of AS model mice. The nanoflare probes possess significant feasibility in the precise identification of atherosclerotic plaques, which holds tremendous implications for clinical diagnosis, mechanism study, and assessment of therapeutic outcomes associated with AS.
动脉粥样硬化（AS）是心血管疾病的主要原因，全球三分之一的死亡与之相关。然而，由于缺乏合适的分析方法，动脉粥样硬化过程仍不清楚。在此，我们展示了首个基于纳米耀斑的DNA传感器，它能够报告ClO（AS的一种典型标志物）在动脉粥样硬化斑块中的分布。将对ClO有响应的硫代磷酸酯（PS）插入DNA中，然后与金纳米颗粒（AuNP）核心组装形成ClO特异性纳米耀斑探针。PS与ClO之间的水解触发了探针的荧光开启，对ClO检测显示出优异的灵敏度（低至8.51 nM）和特异性。此外，纳米耀斑探针在追踪活的RAW264.7细胞内源性和外源性ClO的变化方面表现出卓越性能。静脉注射后，在AS模型小鼠的动脉粥样硬化斑块中观察到探针的有效积累和荧光信号增强。纳米耀斑探针在精确识别动脉粥样硬化斑块方面具有显著的可行性，这对AS相关的临床诊断、机制研究和治疗效果评估具有重大意义。
