Liao Wantao, Wang Chunzheng, Wang Ruiya, Wu Mengzhao, Li Lanqing, Chao Pengjie, Hu Jinhui, Chen Wen-Hua
School of Pharmacy and Food Engineering, Wuyi University, 529020, Jiangmen, PR China.
School of Pharmacy and Food Engineering, Wuyi University, 529020, Jiangmen, PR China.
Anal Chim Acta. 2025 Jan 15;1335:343442. doi: 10.1016/j.aca.2024.343442. Epub 2024 Nov 20.
Drug-induced liver injury (DILI) is one of the most common liver diseases. The crucial role of lipid droplets (LDs) and hydrogen peroxide (HO), two important biomarkers in the pathophysiology of DILI, has spurred considerable efforts to accurately visualize HO and LDs for elucidating their functions in the progression of DILI. However, construction of a single fluorescent probe that is able to simultaneously image HO and LDs dynamics remains to be a challenging task. Therefore, it is of great demand to develop a novel fluorescent probe for tracking the LDs status and HO fluctuation in drug-induced liver injury.
We developed an "AIE + ESIPT" fluorescent probe TPEHBT for dual-imaging of LDs and HO during DILI process. TPEHBT displayed greatly enhanced fluorescent response to HO by generating an excited state intramolecular proton transfer (ESIPT) fluorophore TPEHBT-OH with aggregation induced emission (AIE) properties. TPEHBT exhibits high selectivity, sensitivity (LOD = 4.73 nM) and large Stokes shift (320 nm) to HO. Interestingly, TPEHBT can light up LDs with high specificity. The probe was favorably applied in the detection of endogenous and exogenous HO in living cells, and notably in the simultaneous real-time visualization of HO generation and LDs accumulation during DILI process. Moreover, TPEHBT was able to image HO generation in zebrafish animal model with APAP-induced liver injury.
For the first time, probe TPEHBT was applied in the dual-imaging of HO fluctuation and LDs status in APAP-induced liver injury model in vitro and in vivo. The present findings strongly suggest that TPEHBT is a promising tool for monitoring HO and LDs dynamics in DILI progression.
药物性肝损伤（DILI）是最常见的肝脏疾病之一。脂滴（LDs）和过氧化氢（HO）作为DILI病理生理学中的两个重要生物标志物，其关键作用促使人们为准确可视化HO和LDs以阐明它们在DILI进展中的功能付出了巨大努力。然而，构建一种能够同时成像HO和LDs动态变化的单一荧光探针仍然是一项具有挑战性的任务。因此，开发一种用于跟踪药物性肝损伤中LDs状态和HO波动的新型荧光探针具有迫切需求。
我们开发了一种“AIE + ESIPT”荧光探针TPEHBT，用于在DILI过程中对LDs和HO进行双成像。TPEHBT通过产生具有聚集诱导发光（AIE）特性的激发态分子内质子转移（ESIPT）荧光团TPEHBT-OH，对HO表现出大大增强的荧光响应。TPEHBT对HO具有高选择性、高灵敏度（检测限 = 4.73 nM）和大斯托克斯位移（320 nm）。有趣的是，TPEHBT能够以高特异性点亮LDs。该探针成功应用于活细胞内源性和外源性HO的检测，尤其用于在DILI过程中同时实时可视化HO的产生和LDs的积累。此外，TPEHBT能够在对乙酰氨基酚（APAP）诱导肝损伤的斑马鱼动物模型中成像HO的产生。
首次将探针TPEHBT应用于体外和体内APAP诱导肝损伤模型中HO波动和LDs状态的双成像。本研究结果有力地表明，TPEHBT是监测DILI进展过程中HO和LDs动态变化的一种有前景的工具。
