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用于肝细胞癌成像的次氯酸激活近红外荧光探针的构建。

Construction of HClO activated near-infrared fluorescent probe for imaging hepatocellular carcinoma.

作者信息

Li Songjiao, Wang Peipei, Yang Ke, Liu Ying, Cheng Dan, He Longwei

机构信息

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Cancer Research Institute, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421001, PR China.

Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China.

出版信息

Anal Chim Acta. 2023 Apr 29;1252:341009. doi: 10.1016/j.aca.2023.341009. Epub 2023 Mar 1.

DOI:10.1016/j.aca.2023.341009
PMID:36935131
Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the liver with poor prognosis. In order to improve the prognosis and overall survival of patients with HCC, it is important to identify it at early stage and resect it precisely. Cell microenvironment, active compounds, and enzymes may change during the cancerization of hepatocytes. Hypochlorous acid (HClO), one of the most significant signal molecules in the cellular signaling pathway, plays an important role in many cellular processes. To detect and treat liver cancers, it is imperative to study how HClO levels change in hepatocytes. However, developing fluorescent probes specific to liver cells to detect HClO still challenging. Herein, we designed and synthesized a NIR hepatocyte-specific fluorescent probe (MBH-MT) that displayed excellent optical properties for detecting HClO in biological samples. Cell imaging experiment conducted with the unique probe MBH-MT, showed that the biocompatible sensor is capable of monitoring HClO and distinguishing normal cells from cancer cells (e.g., HepG2, HUVEC, RAW264.7, L02 and HK-2 cells). An organ imaging experiment with the probe MBH-MT demonstrated its effectiveness in diagnosing and imaging hepatocellular carcinoma in vivo. MBH-MT's in situ imaging also demonstrated that it can target and image mouse hepatocellular carcinomas. Furthermore, MBH-MT has also successfully been used to diagnose and guide liver cancer surgery early. In the future, we expect that this powerful tool may be help in the detection and imaging of hepatocellular carcinoma, which may affect a large number of people.

摘要

肝细胞癌(HCC)是肝脏中最常见的恶性肿瘤之一,预后较差。为了改善HCC患者的预后和总生存期,在早期识别并精确切除肿瘤至关重要。在肝细胞癌变过程中,细胞微环境、活性化合物和酶可能会发生变化。次氯酸(HClO)是细胞信号通路中最重要的信号分子之一,在许多细胞过程中发挥着重要作用。为了检测和治疗肝癌,研究HClO在肝细胞中的水平变化势在必行。然而,开发特异性针对肝细胞的荧光探针来检测HClO仍然具有挑战性。在此,我们设计并合成了一种近红外肝细胞特异性荧光探针(MBH-MT),该探针在生物样品中检测HClO时表现出优异的光学性能。使用独特的探针MBH-MT进行的细胞成像实验表明,这种生物相容性传感器能够监测HClO,并区分正常细胞和癌细胞(如HepG2、HUVEC、RAW264.7、L02和HK-2细胞)。用探针MBH-MT进行的器官成像实验证明了其在体内诊断和成像肝细胞癌方面的有效性。MBH-MT的原位成像还表明它可以靶向并成像小鼠肝细胞癌。此外,MBH-MT还成功地用于早期诊断和指导肝癌手术。未来,我们期望这个强大的工具可能有助于肝细胞癌的检测和成像,这可能会影响大量人群。

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