​Construction of a novel AIE NIR fluorescence probe for monitoring lipid droplet dynamics during drug intervention and identification of disease models.

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.