Rational Development of a Lipid Droplets and Hypochlorous Acid In-Sequence Responsive Fluorescent Probe for Accurate Imaging of Atherosclerotic Plaques.

To answer the call for effective and timely intervention in cardiovascular diseases (CVDs), the development of fluorescent probes that can precisely identify atherosclerotic plaques, the root cause of various fatal CVDs, is highly desirable but remains a great challenge. Herein, by integrating bis(trifluoromethyl)benzyl and phenothiazine into the coumarin matrix, a robust fluorescent probe, NOR1, has been developed. NOR1 responds sequentially to lipid droplets (LDs) and HClO via fluorescence turn-on and ratiometric readouts, respectively, with a fast response rate (within 70 s for LDs and 80 s for HClO), excellent sensitivity (detection limit: 0.41 μg/mL for LDs and 23.38 nM for HClO), and high selectivity. Based on these impressive features, NOR1 was successfully applied to discriminate foam cells from others by simultaneously monitoring two hallmark events, lipid accumulation and oxidative stress, in foam cells. Furthermore, the use of NOR1 to monitor in real time the transformation process of A7r5 cells into foam cells under high LDL/glucose conditions was successfully realized for the first time. Importantly, we further demonstrate the ability of NOR1 to precisely identify atherosclerotic plaques with clear margin delineation, highlighting its potential utility in elucidating the pathological mechanism and clinical diagnosis of atherosclerosis.