Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood–brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

中文翻译：

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利用新型线粒体靶向荧光探针实时监测胶质母细胞瘤线粒体粘度异常

由于血脑屏障（BBB）的存在和肿瘤细胞的高侵袭性，胶质母细胞瘤是最致命和隐匿的恶性肿瘤。线粒体粘度异常已被确定为恶性肿瘤的一个关键特征。因此，本研究报告了一种新型线粒体粘度荧光探针，称为ZVGQ，它基于扭曲分子内电荷转移（TICT）效应。该探针使用 3-二氰基甲基-1,5,5-三甲基环己烯作为电子供体部分和分子转子，并使用三苯基膦 (TPP) 阳离子作为电子受体和线粒体靶向基团。ZVGQ具有高选择性、pH 值和时间稳定性，并表现出快速的粘度响应能力。体外实验表明，ZVGQ可以快速识别并检测 U87MG 细胞中制霉菌素和鱼藤酮诱导的线粒体粘度变化，并能够在活 U87MG 细胞中进行长达 12 小时的长期成像。此外，体外3D 肿瘤球和体内原位肿瘤模型表明，探针ZVGQ表现出出色的组织穿透深度和穿透血脑屏障的能力。 ZVGQ探针不仅成功地实现了异常线粒体粘度变化的可视化，而且为胶质母细胞瘤的实时成像和临床诊断提供了实用可行的工具。