Cao Shixian, Ding Qihang, Sun Caixia, Codogno Borbala, Liu Zhiqiang, Yu Xiaoqiang, Kim Jong Seung, Wang Kang-Nan
State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, P.R. China.
Department of Chemistry, Korea University, Seoul, 02841, South Korea.
Angew Chem Int Ed Engl. 2025 Jul;64(29):e202502159. doi: 10.1002/anie.202502159. Epub 2025 May 20.
Dysregulated lipid metabolism plays a critical role in the pathogenesis of numerous diseases. However, due to the lack of effective solutions, the dynamic monitoring and deep understanding of lipid metabolism in those disease progression has remained challenging. Herein, a polarity-sensitive, lipid droplets (LDs)-targeted probe was developed for spatiotemporal super-resolution imaging of lipid metabolism dynamics. Based on the stimulated emission depletion (STED) and fluorescence lifetime imaging microscopy (FLIM) platform, we achieved the super-resolution visualization and dynamic tracking of the nonlinear fusion and expansion mechanisms of LDs in orthotopic pathology models-an unprecedented achievement in the field. We also analyzed lipid distribution in zebrafish models using the STED-FLIM platform to capture lipid metabolism at the organismal level. Crucially, based on the integrated STED-FLIM platform, this probe accurately monitors lipid metabolism in cellular and pathological tissue contexts of atherosclerosis and fatty liver. This breakthrough provides novel insights for diagnosing lipid metabolism-related diseases and advancing therapeutic development.
脂质代谢失调在众多疾病的发病机制中起着关键作用。然而，由于缺乏有效的解决方案，对这些疾病进展过程中脂质代谢的动态监测和深入理解仍然具有挑战性。在此，我们开发了一种极性敏感、靶向脂滴（LDs）的探针，用于脂质代谢动力学的时空超分辨率成像。基于受激发射损耗（STED）和荧光寿命成像显微镜（FLIM）平台，我们在原位病理模型中实现了脂滴非线性融合和扩张机制的超分辨率可视化及动态跟踪，这是该领域前所未有的成就。我们还使用STED-FLIM平台分析了斑马鱼模型中的脂质分布，以在机体水平捕获脂质代谢。至关重要的是，基于集成的STED-FLIM平台，该探针能够准确监测动脉粥样硬化和脂肪肝的细胞及病理组织环境中的脂质代谢。这一突破为诊断脂质代谢相关疾病和推进治疗发展提供了新的见解。
