Rational design of an AIEgen for imaging lipid droplets polarity change during ferroptosis.

Ferroptosis can regulate cell death by accumulating lipid peroxides, affecting the structure and polarity of lipid droplets (LDs), but clear evidence is still lacking. Fluorescence imaging is the most powerful technique for studying LDs' function. However, developing AIE fluorescent probes with high selectivity and sensitivity for targeting LDs remains challenging. In this study, we rationally designed an AIEgen, as a novel fluorescent probe TPE-BD, by constructing a push-pull electron structure. The probe has benzo[b]thiophene-3(2H)-one 1,1-dioxide as the electron acceptor, tetraphenylethylene (AIE skeleton) as the electron donor, and thiophene as the bridging group. The optical performance of probe TPE-BD indicated that the UV-visible absorption spectrum of the probe was minimally affected by solvent polarity (except for glycerol and PBS solvents), but the fluorescence of probe is very sensitive to changes in polarity, achieving the goal of polarity detection in LDs. CCK-8 assay and cell imaging experiments demonstrated that probe TPE-BD exhibited good cell compatibility and effectively targeted LDs, enabling the monitoring of LDs' polarity and quantity during ferroptosis.