School of Pharmacy, Wannan Medical College, Wuhu 241002, China.
Huaxi MR Research Centre (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610000, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2024 Dec 15;323:124918. doi: 10.1016/j.saa.2024.124918. Epub 2024 Jul 31.
The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.
溶酶体中癌细胞的黏度较高，pH 值较低，这突出了它们作为癌症标志物的潜力。因此，开发酸激活黏度荧光探针对于癌症的早期诊断和治疗具有重要意义。基于此，我们设计并合成了一种基于 2-(2-羟基苯基)苯并噻唑（HBT）基团的近红外荧光探针，即 HBTH，以监测溶酶体内的黏度变化。研究表明，HBTH 对黏度极其敏感，荧光强度与（logη）范围内的对数黏度之间存在很强的线性关系（相关系数为 0.98），证明其具有定量测量黏度的能力。特别是，HBTH 的最明显荧光增强仅能被低 pH 值和高黏度的联合作用有效触发。此外，HBTH 可以在低浓度（100 nM）下通过无洗涤程序快速定位到溶酶体，并在 20 s 内实现高保真成像。它还可以监测细胞中溶酶体的动态过程、药物刺激下的黏度变化以及细胞自噬过程中的溶酶体行为。重要的是，HBTH 能够通过体内成像在荷瘤裸鼠中识别肿瘤。这些特点使 HBTH 成为癌症早期诊断和治疗的有力工具。
