Yang Zhi-Chao, Yang Zhi-Hao, Wang Zhi-Qing, Li Yao, Mao Guo-Jiang, Hu Liufang, Ouyang Juan, Li Chun-Yan
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, Hunan Provincial University Key Laboratory for Environmental and Ecological Health, College of Chemistry, Xiangtan University, Xiangtan 411105, P.R. China.
Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P.R. China.
Anal Chem. 2025 Jan 14;97(1):185-193. doi: 10.1021/acs.analchem.4c03540. Epub 2025 Jan 3.
The challenge of "false positive" signals significantly complicates tumor localization and surgical resection, which are pivotal for successful tumor surgeries. Therefore, the development of a method for preoperative tumor localization and intraoperative margin determination holds considerable promise for improving surgical outcomes. In this study, a zero-crosstalk ratiometric tumor-targeting near-infrared (NIR) fluorescent probe was developed for precise cancer diagnosis and intraoperative navigation via NIR fluorescence imaging. This probe integrates a tumor-targeting moiety that selectively homes in on hepatocellular carcinoma cells and exhibits a highly sensitive ratiometric response to γ-glutamyltranspeptidase (GGT), characterized by a substantial emission shift from 830 to 650 nm. This unique NIR ratiometric emission property significantly enhances its effectiveness in early diagnosis and imaging-guided surgery resection. Furthermore, this zero-crosstalk probe successfully monitors GGT activity in blood, cells, and in vivo, endowing its potential for early cancer diagnosis in the clinic. Due to its efficient targeting and sensitive in situ response to GGT in both subcutaneous tumors and orthotopic hepatic tumors, the probe exhibits accurate detection capability for hepatic tumors. Additionally, by leveraging zero-crosstalk ratiometric NIR fluorescence imaging, this tumor-targeting probe can serve as a sprayable tool for delineating tumor margins with precision, thereby furnishing real-time intraoperative imaging guidance during tumor resection surgery.
“假阳性”信号带来的挑战显著增加了肿瘤定位和手术切除的复杂性，而这对于成功的肿瘤手术至关重要。因此，开发一种术前肿瘤定位和术中切缘确定的方法对于改善手术结果具有很大的前景。在本研究中，开发了一种零串扰比率型肿瘤靶向近红外（NIR）荧光探针，用于通过NIR荧光成像进行精确的癌症诊断和术中导航。该探针整合了一个肿瘤靶向部分，该部分选择性地定位于肝癌细胞，并对γ-谷氨酰转肽酶（GGT）表现出高度敏感的比率响应，其特征是发射波长从830 nm大幅移至650 nm。这种独特的近红外比率发射特性显著提高了其在早期诊断和影像引导手术切除中的有效性。此外，这种零串扰探针成功地监测了血液、细胞和体内的GGT活性，赋予了其在临床中早期癌症诊断的潜力。由于其在皮下肿瘤和原位肝肿瘤中对GGT具有高效靶向和敏感的原位响应，该探针对肝肿瘤具有准确的检测能力。此外，通过利用零串扰比率型近红外荧光成像，这种肿瘤靶向探针可以作为一种可喷涂工具精确勾勒肿瘤边缘，从而在肿瘤切除手术中提供实时术中影像引导。
