An AND-gate bioluminescent probe for precise tumor imaging

Chenchen Wang; Yajian Hong; Ling Dong; Hu Cheng; Duo Jin; Ronghua Zhao; Zian Yu; Yue Yuan

doi:10.1039/d3sc00556a

An AND-gate bioluminescent probe for precise tumor imaging

Chem Sci. 2023 May 3;14(21):5768-5773. doi: 10.1039/d3sc00556a. eCollection 2023 May 31.

Authors

Chenchen Wang¹, Yajian Hong¹, Ling Dong², Hu Cheng¹, Duo Jin¹, Ronghua Zhao³, Zian Yu¹, Yue Yuan¹

Affiliations

¹ Department of Chemistry, University of Science and Technology of China 96 Jinzhai Road Hefei Anhui 230026 China yueyuan@ustc.edu.cn.
² Department of Chemistry and Chemical Engineering, Hefei Normal University Hefei Anhui 230061 China.
³ Center for Biomedical Imaging, University of Science and Technology of China Hefei Anhui 230026 China.

Abstract

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.