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近红外荧光探针用于活体肝组织中 HClO 的选择性成像。

Selective Imaging of HClO in the Liver Tissue In Vivo Using a Near-infrared Hepatocyte-specific Fluorescent Probe.

机构信息

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Wusi Dong Road 18, Baoding, 071002, P. R. China.

Medical Comprehensive Experimental Center, Hebei University, East Road Yuhua 342, Baoding, 071000, P. R. China.

出版信息

Chem Asian J. 2021 Jul 19;16(14):1967-1972. doi: 10.1002/asia.202100476. Epub 2021 Jun 7.

Abstract

Liver injury is typified by an inflammatory response. Hypochlorous acid (HClO), an important endogenous reactive oxygen species, is regarded as a biomarker associated with liver injury. Near-infrared (NIR) fluorescent probes with the advantage of deep tissue penetrating and low auto-fluorescence interference are more suitable for bioimaging in vivo. Thus, in this work, we designed and synthesized a novel NIR hepatocyte-specific fluorescent probe named NHF. The probe NHF showed fast response (<3 s), large spectral variation, and good selectivity to trace HClO in buffer solution. By employing N-acetylgalactosamine (GalNAc) as the targeting ligand, probe NHF can be actively delivered to the liver tissue of zebrafish and mice. It is important that probe NHF is the first NIR hepatocyte-specific fluorescent probe, which successfully visualized the up-regulation of endogenous HClO in the oxygen-glucose deprivation/reperfusion (OGD/R) model HepG2 cells and dynamically monitored APAP-induced endogenous HClO in the liver tissue of zebrafish and mice.

摘要

肝损伤的特点是炎症反应。次氯酸(HClO)作为一种重要的内源性活性氧物质,被认为是与肝损伤相关的生物标志物。具有组织穿透能力深和自体荧光干扰低优势的近红外(NIR)荧光探针更适合于体内生物成像。因此,在这项工作中,我们设计并合成了一种新型的 NIR 肝细胞特异性荧光探针,命名为 NHF。探针 NHF 在缓冲溶液中对痕量 HClO 表现出快速响应(<3 s)、大光谱变化和良好的选择性。通过使用 N-乙酰半乳糖胺(GalNAc)作为靶向配体,探针 NHF 可以主动递送到斑马鱼和小鼠的肝组织中。重要的是,探针 NHF 是第一个 NIR 肝细胞特异性荧光探针,成功地可视化了氧葡萄糖剥夺/再灌注(OGD/R)模型 HepG2 细胞中内源性 HClO 的上调,并动态监测了斑马鱼和小鼠肝组织中 APAP 诱导的内源性 HClO。

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