Polarity-Tuned Lipid Droplet-Specific Probe for Heart Failure Imaging

Heart failure (HF) is the ultimate development trend of most cardiovascular diseases, and a poor prognosis would result in serious consequences. Lately, the involvement of lipid droplets (LDs) in cardiovascular pathogenesis has garnered growing scientific recognition. Aberrant polarity alterations of LDs may destroy the balance of lipid metabolism, which is mechanistically linked to the occurrence and development of HF. In this investigation, we engineered and synthesized the probe WT-X utilizing the BODIPY scaffold, a polarity-sensitive molecular tool featuring a donor-π-acceptor (D-π-A) architectural framework, which exhibits good photostability, excellent biocompatibility, and high selectivity to polarity. WT-X demonstrated sensitive detection of aberrant lipid droplet polarity alterations in HF cardiomyocyte models, yolk sac region of inflamed live zebrafish, and the myocardial LDs in mice with HF. This discovery facilitates noninvasive visualization of pathological lipid metabolism for precision HF management, enabling real-time therapeutic efficacy monitoring and patient stratification.