Visualizing polarity changes during ferroptosis via a red-emitting BODIPY probe for targeted lipid droplet imaging in live cells.

Ferroptosis is a regulated form of cell death driven by the progressive accumulation of lipid peroxides induced by reactive oxygen species, and has now garnered extensive attention in various pathological research contexts. During the initiation and progression of ferroptosis, the polarity of lipid droplets (LDs) is affected and undergoes alterations. Therefore, developing an effective tool that enables high-fidelity fluorescence detection holds significant research value for the early diagnosis of ferroptosis-associated diseases. In this study, a LD-targeting BODIPY-based fluorescent probe K2 was designed and synthesized. Its photophysical properties and bioimaging performance were systematically investigated. Specifically, probe K2 adopts carbazole-triphenylamine as the electron-donating unit and trifluoromethylphenyl group as the electron-acceptor moiety, constructing an electronic push-pull system. Benefiting from the intramolecular charge transfer (ICT) effect, this probe exhibits red-emitting fluorescence and polarity-responsive characteristics: its fluorescence is quenched in high-polarity solvents, while strong fluorescence emission can be observed in low-polarity environments. Moreover, K2 showed high selectivity for environmental polarity over viscosity and other biomolecules. Cell experiments demonstrated that K2 possessed excellent LD-targeting specificity and low cytotoxicity. The probe enabled real-time monitoring of dynamic LD polarity fluctuations under various physiological and pathological conditions. In particular, real-time tracking of LD polarity variations during ferroptosis was achieved. Thus, this work offers a robust tool to decipher the function of cellular polarity during ferroptosis.