Polarity Sensitive and <scp>H₂O₂</scp>/Lipid Droplets Sequence‐Activated Asymmetric Cyanine Probe Achieves Multi‐marker Imaging of Atherosclerosis

Comprehensive Summary Atherosclerosis is a lipoprotein‐driven disease. In‐depth understanding of pathology and accurate identification are particularly important in clinical assessment and treatment due to the irreversibility of atherosclerotic plaque formation. Atherosclerosis is not only accompanied by lipid droplets accumulation but also closely related to inflammation, which is accompanied by excessive reactive oxygen species (ROS) and changes in microenvironment. However, there is still a lack of a simple and rapid detection platform to simultaneously evaluate multiple indicators of atherosclerosis in multiple channels. In this study, we propose a multicolor imaging probe Cy7P‐B for polarity, H 2 O 2 and lipid droplets to evaluate atherosclerotic plaques in vivo . Cy7P‐B is sensitive to environmental polarity and can monitor polarity changes by near‐infrared ratio. Moreover, Cy7P‐B has H 2 O 2 /lipid droplets dual‐analyte sequential activation characteristics. Based on the multifunctional properties of Cy7P‐B , the classical biomarkers of atherosclerotic plaque, lipid accumulation and up‐regulation of oxidative stress are effectively detected in atherosclerotic plaques, and more importantly, the change of aortic polarity in atherosclerosis was detected for the first time. This work provides a general molecular design approach for multi‐species imaging of AS, which is helpful for effective cardiovascular disease stewardship.