Zheng Fan, Yao Heying, Fan Duoyang, Huang Shuai, Fang Yanpeng, Bi Anyao, Bai Shuaige, Zhang Shengwang, Zou Hui, Chen Fei, Zeng Wenbin
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Central South University, Changsha 410013, PR China.
J Med Chem. 2025 Apr 24;68(8):8471-8483. doi: 10.1021/acs.jmedchem.5c00020. Epub 2025 Apr 2.
Hepatocellular carcinoma (HCC) poses a global challenge due to the lack of accurate early stage detection methods. Carboxylesterase (CE), a key HCC biomarker, presents an ideal target for HCC diagnosis. Herein, we developed a novel CE-sensitive fluorescent probe () that offered powerful near-infrared fluorescence signals and a potent synergistic photodynamic/chemodynamic therapeutic effect against HCC. This probe was synthesized by linking ferrocenecarboxylic acid (a Fenton reagent) to (a photosensitizer) through a self-eliminating spacer. This activation enabled ratiometric fluorescence imaging of CE, allowing for specific differentiation of HCC cells from others, exceeding the capabilities of commercial kits. Moreover, could generate O and OH upon CE activation in vitro, triggering both apoptosis and ferroptosis in cancer cells. Remarkably, enabled real-time tumor visualization and effective tumor growth inhibition in vivo. This study showcased the promise of as a versatile tool for advancing precision medicine in HCC.
由于缺乏准确的早期检测方法，肝细胞癌（HCC）构成了一项全球性挑战。羧酸酯酶（CE）作为一种关键的HCC生物标志物，是HCC诊断的理想靶点。在此，我们开发了一种新型的对CE敏感的荧光探针（），它能提供强大的近红外荧光信号，并对HCC具有强大的协同光动力/化学动力治疗效果。该探针通过一个自消除间隔基将二茂铁羧酸（一种芬顿试剂）与（一种光敏剂）连接而成。这种活化实现了CE的比率荧光成像，能够特异性地区分HCC细胞与其他细胞，超越了商业试剂盒的能力。此外，在体外CE活化时可产生O和OH，触发癌细胞的凋亡和铁死亡。值得注意的是，在体内能够实现实时肿瘤可视化并有效抑制肿瘤生长。这项研究展示了作为推进HCC精准医学的多功能工具的前景。
