Dual-Locked Chemiluminescent Probe Enables Precise Imaging and Timely Diagnosis of Colitis via Chymotrypsin/Vanin-1 Cascade Activation

The development of precise diagnosis and the discovery of individualized drugs go together to provide effective therapy against inflammatory bowel disease (IBD). The exploitation of the unique imaging advantages of chemiluminescent probes represents a pivotal strategy for achieving this goal. Nevertheless, the dual-locked strategy, which is believed to enhance precision, is rarely employed in the design of chemiluminescent probes. A novel dual-locked chemiluminescent probe, <b>BPan-CL</b>, was designed based on IBD candidate biomarkers chymotrypsin (CHT) and vanin-1. <b>BPan-CL</b> exhibited specific reactivity and chemiluminescence response when subjected to simultaneous stimulation of CHT and vanin-1, with a signal-to-noise ratio superior to that of the fluorescent probe with the same dual-locked mode. In both live cell and IBD mice imaging, <b>BPan-CL</b> demonstrated superior sensitivity compared to its single-locked counterpart, <b>Pan-CL</b>. In contrast to <b>Pan-CL</b>, <b>BPan-CL</b> was able to more accurately identify IBD and healthy mice by in vivo imaging and allowed for early prediction of IBD using a noninvasive fecal test. <b>BPan-CL</b> has identified CHT and vanin-1 as valuable combinatorial biomarkers for accurate and early IBD diagnosis. This strategy has significant potential for use in biomedical imaging and future individualized therapies.