Li Xinming, Hou Yanan, Zhang Fang, Zhao Jintao, Liu Yunlong, Liu Yu, Liu Qile, Chen Xin, Fang Jianguo
School of Chemistry and Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, China.
School of Pharmacy, Changzhou University, Changzhou, Jiangsu, 213164, China.
Anal Chim Acta. 2025 Sep 22;1368:344328. doi: 10.1016/j.aca.2025.344328. Epub 2025 Jun 14.
Lipid peroxidation (LPO) and abnormal accumulation of lipid droplets (LDs) are key pathogenic factors contributing to the onset and progression of multiple diseases. Fluorescent probes for monitoring LPO and LDs accumulation are promising tools for the early diagnosis of related diseases, providing valuable insights that could lead to improved disease management and therapeutic strategies. However, to the best of our knowledge, a dual-channel fluorescent probe capable of simultaneously monitoring LPO and LD accumulation has not yet been reported.
We rationally designed and synthesized a dual-responsive fluorescent probe, Cou-LPO4, for simultaneous visualization of LPO and LDs in living cells. Cou-LPO4 exhibits green fluorescence at 560 nm in response to lipid peroxyl radicals (LOO•) with excellent selectivity and sensitivity, and red fluorescence at 640 nm in response to LDs accumulation. Cou-LPO4 was successfully applied to evaluate LPO during RSL3-and erastin-induced ferroptosis by monitoring fluctuations in LOO• levels. Subsequently, using Cou-LPO4, we revealed a significant upregulation of LPO, accompanied by a marked accumulation of LDs in nonalcoholic fatty liver disease (NAFLD) cell model.
Cou-LPO4 is the first dual-channel fluorescent probe enabling simultaneous monitoring of LPO and LDs accumulation in living cells. It provides a powerful tool for studying LPO and LDs accumulation-related diseases like NAFLD, offering new insights for early diagnosis and therapeutic strategies.
脂质过氧化（LPO）和脂滴（LDs）的异常积累是导致多种疾病发生和发展的关键致病因素。用于监测LPO和LDs积累的荧光探针是相关疾病早期诊断的有前景的工具，可为改善疾病管理和治疗策略提供有价值的见解。然而，据我们所知，尚未报道能够同时监测LPO和LDs积累的双通道荧光探针。
我们合理设计并合成了一种双响应荧光探针Cou-LPO4，用于在活细胞中同时可视化LPO和LDs。Cou-LPO4在560 nm处对脂质过氧自由基（LOO•）表现出绿色荧光，具有优异的选择性和灵敏度，在640 nm处对LDs积累表现出红色荧光。通过监测LOO•水平的波动，Cou-LPO4成功应用于评估RSL3和埃拉司亭诱导的铁死亡过程中的LPO。随后，使用Cou-LPO4，我们揭示了在非酒精性脂肪性肝病（NAFLD）细胞模型中LPO显著上调，同时伴有LDs的明显积累。
Cou-LPO4是第一种能够同时监测活细胞中LPO和LDs积累的双通道荧光探针。它为研究如NAFLD等与LPO和LDs积累相关的疾病提供了一个强大的工具，为早期诊断和治疗策略提供了新的见解。
