All-Nontoxic Fluorescent Probe for Biothiols and Its Clinical Applications for Real-Time Glioblastoma Visualization

• DOI: 10.1021/acssensors.3c00004
• Publication Date: 2023-03-27T04:39:27Z
• Authors: Youngwoong Kim; Jaehoon Kim; Jong Min An; Chul-Kee Park; Dokyoung Kim
• Keywords: Biocompatibility

Fluorescence-guided surgery (FSG) is a surgical method to selectively visualize the tumor site using fluorescent materials with instrumental setups in operation rooms. It has been widely used of brain tumors, such as glioblastoma (GBM), which difficult distinguish from normal tissue. Although FSG crucial for GBM surgery, commercially available have shown serious adverse effects. To satisfy clinical demand, we recently reported reaction-based probes based on 4-chloro-7-nitrobenzofurazan (NBD) fluorophore that can detect cysteine (Cys) and homocysteine (Hcy), biomarker GBM, their applications diagnosis FSG. However, our cellular toxicity issues arising leaving group (LG) generated after reaction probe analytes. In this study, disclosed nontoxic sensing biothiols real-time human visualization. Systematic analysis several LGs was conducted cell lines. Among LGs, 2-hydroxy-pyridine showed negligible toxicity, its derivative (named NPO-o-Pyr) high specificity sensitivity (LOD: 0.071 ppm Cys; 0.189 Hcy), fast response time (<5 min) Cys Hcy, biocompatibility. addition, NPO-o-Pyr significantly both actual samples well GBM-xenografted mouse model. We are confident will become new substitute due capability overcome limitations current probes.