Real-time monitoring of lipid droplets (LDs) dynamics is critical for elucidating lipid metabolic pathways enabling early diagnosis of related diseases. In this study, we developed three novel donor-acceptor (D-π-A) type aggregation-induced emission (AIE) near-infrared (NIR) fluorescent probes, namely TPA-T1 , TPA-T2 , and TPA-T3 . Among them, TPA-T2 exhibited the most pronounced fluorescence enhancement and excellent lipophilicity, enabling real-time visualization of LDs fluctuations in living cells. Experimental results demonstrated that TPA-T2 not only effectively tracked LDs dynamics but also revealed the functional involvement of LDs in cell death pathways such as ferroptosis and cuproptosis. Furthermore, TPA-T2 displayed a high degree of sensitivity to drug-induced metabolic changes, effectively distinguish normal liver tissue from fatty liver tissue, offering a valuable tool for pharmacodynamic assessment and early diagnosis of lipid metabolism-related diseases. When applied to tumor models, TPA-T2 was able to selectively label LDs within tumor tissues, underscoring its potential for studying tumor metabolic phenotypes. Overall, this work provides a novel molecular imaging tool for elucidating the mechanisms of metabolic diseases and offers broad application prospects in lipid metabolism research, cancer biology, and disease diagnostics.
Wang et al. (Sat,) studied this question.