BODIPY-based fluorescent probes distinguish the heterogeneity of lipid droplets in carotid and femoral atherosclerotic plaques

Atherosclerosis (AS), a complex and long-term disease, is a major contributor to cardiovascular complications and a leading cause of death across the globe. Lipid droplets (LDs) are closely involved in the initiation and development of AS plaques. Therefore, visualization and quantification of the complexity of LDs may assist in understanding the biology of atherosclerotic plaques and assessing lesion stability. In this study, we report lipophilic fluorescent sensors based on a BODIPY scaffold (<i>P</i>1 & <i>P</i>2). These probes exhibited fluorescence responsiveness in oil/water systems and lipid droplet mimics (LDMs), with detection limits as low as 50 μg mL^-1. In a cellular milieu, the probes effectively tracked LD accumulation induced by oxidized low-density lipoprotein (ox-LDL) as well as lipid suppression caused by treatment with rosiglitazone. <i>Ex vivo</i> imaging of atherosclerotic plaques in ApoE^-/- mice and human tissues further demonstrated that these probes could distinguish pathological characteristics across various vascular regions. Collectively, these results highlight the first application of LD sensors in sensing the distinct lipidic lesions in biopsied atherosclerotic plaques from patients, suggesting an organ-specific pathogenesis.