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<p>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 <b>TPA-T1</b>, <b>TPA-T2</b>, and <b>TPA-T3</b>. Among them, <b>TPA-T2</b> exhibited the most pronounced fluorescence enhancement and excellent lipophilicity, enabling real-time visualization of LDs fluctuations in living cells. Experimental results demonstrated that <b>TPA-T2</b> not only effectively tracked LDs dynamics but also revealed the functional involvement of LDs in cell death pathways such as ferroptosis and cuproptosis. Furthermore, <b>TPA-T2</b> 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, <b>TPA-T2</b> 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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年1月17日

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  • Yuqing Wang,
  • Zhiyu Wang,
  • Kun Yu,
  • Jing Yang,
  • Qi Su,
  • Jie Wang,
  • Lei Hu,
  • Hui Wang

摘要

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.

Graphical Abstract