State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Analyst. 2022 Sep 26;147(19):4257-4265. doi: 10.1039/d2an01115h.
Cysteine (Cys), a small-molecule biothiol, has recently been identified as a novel Glioblastoma (GBM) biomarker. The highly selective real-time monitoring and fluorescence imaging of Cys levels is of great significance for the early diagnosis and treatment of GBM. In this work, we reported a highly selective Cys fluorescent probe ZS-C1, based on quinoline according to the mechanism of the conjugate addition cyclization reaction. The Limit of Detection (LOD) of probe ZS-C1 was 1.97 μM, = 380 nm; = 531 nm. experiments showed that ZS-C1 could be distinguished from Hcy and GSH significantly, and the fluorescence quantum yield was reduced by 30 times. Further, biological imaging and 3D tumor sphere penetration assay showed that the ZS-C1 could monitor both exogenous and endogenous Cys in the living U87MG cells, and the fluorescence of probe ZS-C1 diffusely distributed inside the U87MG three-dimensional solid cell spheroid (up to 60 μM deep into the solid tumors). This work provided a potential tool for further investigations of Cys in biological samples and critical information for early diagnosis of glioma and guidance for clinical surgery.
半胱氨酸(Cys),一种小分子生物硫醇,最近被确定为神经胶质瘤(GBM)的新型生物标志物。对半胱氨酸水平的高选择性实时监测和荧光成像对 GBM 的早期诊断和治疗具有重要意义。在这项工作中,我们根据共轭加成环化反应的机制,基于喹啉报道了一种高选择性的 Cys 荧光探针 ZS-C1。探针 ZS-C1 的检测限(LOD)为 1.97 μM,λex = 380nm;λem = 531nm。实验表明,ZS-C1 可以与 Hcy 和 GSH 明显区分,荧光量子产率降低了 30 倍。此外,生物成像和 3D 肿瘤球穿透实验表明,ZS-C1 可以监测活 U87MG 细胞中外源和内源性 Cys,探针 ZS-C1 的荧光在 U87MG 三维固体细胞球体内弥漫分布(深入固体肿瘤达 60 μM)。这项工作为进一步研究生物样品中的 Cys 提供了潜在的工具,并为神经胶质瘤的早期诊断和临床手术指导提供了关键信息。