An AND-gate bioluminescent probe for precise tumor imaging

• Published in: Chemical science (Cambridge) 2023-05, Vol.14 (21), p.5768-5773
• Main Authors: Wang, Chenchen, Hong, Yajian, Dong, Ling, Cheng, Hu, Jin, Duo, Zhao, Ronghua, Yu, Zian, Yuan, Yue
• Format: Article
• Language: English
• Subjects: Bioluminescence; Biomarkers; Chemistry; Correlation analysis; Medical imaging; Sensitivity; Tumors
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc00556a

Sensitivity and specificity are two indispensable requirements to ensure diagnostic accuracy. Dual-locked probes with "AND-gate" logic theory have emerged as a powerful tool to enhance imaging specificity, avoid "false positive" results, and realize correlation analysis. In addition, bioluminescence imaging (BLI) is an excitation-free optical modality with high sensitivity and low background and can thus be combined with a dual-locked strategy for precise disease imaging. Here, we developed a novel AND-gate bioluminescent probe, FK-Luc-BH , which is capable of responding to two different tumor biomarkers (cathepsin L and ClO − ). The good specificity of FK-Luc-BH was proven, as an obvious BL signal could only be observed in the solution containing both cathepsin L (CTSL) and ClO − . 4T1-fLuc cells and tumors treated with FK-Luc-BH exhibited significantly higher BL signals than those treated with unresponsive control compound Ac-Luc-EA or cotreated with FK-Luc-BH and a ClO − scavenger/cathepsin inhibitor, demonstrating the ability of FK-Luc-BH to precisely recognize tumors in which CTSL and ClO − coexist. An AND-gate bioluminescent probe FK-Luc-BH was constructed by integrating excitation-free BLI modality with a dual-locked strategy to monitor the co-localization of cathepsin L and hypochlorite in tumor sites for precise tumor imaging.