Synergistically\nActivated Aggregation-Induced Emission\nProbe for Precise In Situ Staining of Lipids in Atherosclerotic Plaques

Visualizing the localization and distribution of lipids\nwithin\narteries is crucial for studying atherosclerosis. However, existing\nlipid-specific probes face challenges such as strong hydrophobicity\nand nonspecific staining of lipophilic organelles or tissues, making\nthem impractical for the precise identification of atherosclerotic\nplaques. To address this issue, we design a synergistically activated\nprobe, Cbz-Lys-Lys-TPEB, which responds to cathepsin B (CTB) and H<sub>2</sub>O<sub>2</sub> for the in situ generation of aggregation-induced\nemission luminogens (AIEgens). This enables specific staining of lipids\nwithin arteries and precise imaging of atherosclerotic plaques. The\nprobe combines a tetraphenylethene building block with a hydrophilic\npeptide sequence (Cbz-Lys-Lys) and phenylboric acid module, providing\nexcellent water solubility and fluorescence quenching in a molecular\ndispersion state. Upon interaction with H<sub>2</sub>O<sub>2</sub> and CTB within plaques, the hydrophilic Cbz-Lys-Lys-TPEB probe is\nspecifically cleaved and converted into hydrophobic AIEgens, leading\nto rapid aggregation and significant fluorescence enhancement. Interestingly,\nthe in situ-liberated AIEgens display distinct lipid binding ability,\neffectively tracking the location and distribution of lipids in plaques.\nThis synergistic target-activated AIEgen liberation strategy demonstrates\nsignificant feasibility for the reliable and accurate identification\nof atherosclerotic plaques, holding tremendous potential for clinical\ndiagnosis and risk stratification of atherosclerosis.