An aggregation-induced emission fluorescent probe for selective lipid droplet imaging and real-time visualization of stress-related lipid metabolism

Lipid droplets (LDs) are dynamic organelles essential for cellular energy homeostasis and lipid metabolism. Dysregulation of LDs has been increasingly associated with a range of diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, in which abnormal lipid accumulation and oxidative stress are common features. Despite their biological importance, available tools for real-time, high-fidelity visualization of LD dynamics in living systems remain limited. In this study, we developed TPA-LDs, an aggregation-induced emission (AIE) fluorescent probe for LD imaging. The probe adopts a donor-π-acceptor (D-π-A) structure and operates through an intramolecular charge transfer (ICT) mechanism, which contributes to its resistance to photobleaching under the imaging conditions, LD selectivity, and sensitivity to low-polarity environments characteristic of LDs. We show that TPA-LDs can selectively label LDs in live A549 cells and plant tissues, enabling real-time visualization of LD dynamics under physiological and pathological conditions, including nutrient stimulation, oxidative stress, and ferroptosis. Owing to the central role of LDs in stress responses and lipid metabolism, TPA-LDs may provide a useful imaging tool for investigating LD-associated biological processes and their relevance to human diseases, including disorders of the nervous system.