State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Centre for Cell Responses, Research Centre for Analytical Sciences, College of Chemistry, Nankai University, Tianjin 300071, P. R. China.
School of Water Conservancy and Environment, University of Jinan, Jinan 250022, P. R. China.
Anal Chem. 2024 May 7;96(18):6968-6977. doi: 10.1021/acs.analchem.3c05940. Epub 2024 Apr 25.
The assessment of atherosclerosis (AS) progression has emerged as a prominent area of research. Monitoring various pathological features of foam cell (FC) formation is imperative to comprehensively assess AS progression. Herein, a simple enzopiropyran-uloliine-based probe, , with switchable dual-color imaging ability was developed. This probe can dynamically and reversibly adjust its molecular structure and fluorescent properties in different polar and pH environments. Such a polarity and pH dual-responsive characteristic makes it superior to single-responsive probes in dual-color imaging of lipid droplets (LDs) and lysosomes as well as monitoring their interaction. By simultaneously tracking various pathological features, including LD accumulation and size changes, lysosome dysfunction, and dynamically regulated lipophagy, more comprehensive information can be obtained for multiparameter assessment of FC formation progression. Using , not only the activation of lipophagy in the early stages and inhibition in the later phases during FC formation are clearly observed but also the important roles of lipophagy in regulating lipid metabolism and alleviating FC formation are demonstrated. Furthermore, is demonstrated to be capable of rapidly imaging FC plaque sites in AS mice with fast pharmacokinetics. Altogether, holds great promise as a dual-color organelle-imaging tool for investigating disease-related LD and lysosome changes and their interactions.
动脉粥样硬化（AS）进展的评估已成为研究的重点领域。监测泡沫细胞（FC）形成的各种病理特征对于全面评估 AS 进展至关重要。在此，我们开发了一种简单的基于 enzopiropyran-uloliine 的探针 ，具有可切换的双色成像能力。该探针可以在不同极性和 pH 环境下动态且可逆地调节其分子结构和荧光性质。这种极性和 pH 双重响应特性使其在脂质滴（LD）和溶酶体的双色成像以及监测它们的相互作用方面优于单响应探针。通过同时跟踪各种病理特征，包括 LD 积累和大小变化、溶酶体功能障碍以及动态调节的自噬，可以获得更全面的信息，用于 FC 形成进展的多参数评估。使用 ，不仅可以清楚地观察到 FC 形成过程中早期的自噬激活和后期的自噬抑制，还可以证明自噬在调节脂质代谢和减轻 FC 形成中的重要作用。此外， 被证明能够快速对 AS 小鼠的 FC 斑块部位进行成像，具有快速的药代动力学特性。总之， 作为一种用于研究与疾病相关的 LD 和溶酶体变化及其相互作用的双色细胞器成像工具具有广阔的应用前景。
