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.