Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.
University of Science and Technology Beijing, School of Materials Science and Engineering, Beijing 100083, PR China.
Spectrochim Acta A Mol Biomol Spectrosc. 2023 Dec 15;303:123225. doi: 10.1016/j.saa.2023.123225. Epub 2023 Aug 2.
Precise detection of inflammatory microenvironment-related viscosity and hypochlorous acid (HClO) contributes to illuminating the pathogenesis and further diagnosing of atherosclerosis (AS). Herein, a dual-lock-controlled mitochondria-targeted fluorescence probe (NS) for simultaneous imaging of HClO and viscosity in AS-related foam cells is presented. NS performs linear increase in green-fluorescence along with increased viscosity (excited at 425 nm), permitting "off-on" fluorescence imaging of viscosity. Meanwhile, upon HClO activation, NS exhibits red-shifted and enhanced fluorescence in orange, thus leading to ratiometric fluorescence quantification of HClO (excited at 465 nm). Such dual-lock-controlled effect makes NS realize simultaneous imaging of viscosity and HClO with high sensitivity and selectivity via "off-on" and ratiometric fluorescence readouts, respectively. Besides, endowed with mitochondria-targeting capacity, NS achieves in situ imaging of mitochondria viscosity and HClO in living RAW264.7 cells. Importantly, for the first time, NS realizes simultaneous imaging of mitochondria viscosity and HClO in macrophage-derived foam cells, revealing the close association between HClO level and viscosity change in mitochondria during foaming translation of macrophages in atherogenesis. This work not only provides a novel strategy and tool to image organelle-located viscosity and HClO in living systems, but also holds great potential in early diagnosis of AS.
精确检测炎症微环境相关的粘度和次氯酸（HClO）有助于阐明动脉粥样硬化（AS）的发病机制和进一步诊断。在此，提出了一种用于同时成像 AS 相关泡沫细胞中 HClO 和粘度的双锁控线粒体靶向荧光探针（NS）。NS 随着粘度的增加（在 425nm 处激发），在绿色荧光中呈线性增加，允许进行粘度的“关-开”荧光成像。同时，在 HClO 激活后，NS 在橙色中表现出红移和增强的荧光，从而实现 HClO 的比率荧光定量（在 465nm 处激发）。这种双锁控效应使 NS 通过“关-开”和比率荧光读出分别实现粘度和 HClO 的高灵敏度和选择性的同时成像。此外，由于具有靶向线粒体的能力，NS 能够在活 RAW264.7 细胞中实现线粒体粘度和 HClO 的原位成像。重要的是，首次在巨噬细胞源性泡沫细胞中实现了线粒体粘度和 HClO 的同时成像，揭示了在动脉粥样形成过程中巨噬细胞泡沫转化过程中线粒体中 HClO 水平和粘度变化之间的密切关联。这项工作不仅为在活系统中成像细胞器定位的粘度和 HClO 提供了一种新的策略和工具，而且在 AS 的早期诊断中具有很大的潜力。
