An intestinal-targeting near-infrared probe for imaging nitroreductase in inflammatory bowel disease

Inflammatory bowel disease (IBD) is an intestinal disease that causes inflammation of the digestive tract, resulting in a lack of oxygen in the intestinal microenvironment. Within this hypoxic setting, nitroreductase (NTR) is overexpressed and serves as a valuable biomarker for IBD. To date, there are only a limited number of fluorescent probes developed for NTR detection in cases of colitis. Unfortunately, they are unable to target the intestinal site and specifically image IBD. In this work, an intestinal-targeting near-infrared fluorescence probe was designed and synthesized for imaging NTR in IBD. Following its interaction with NTR, Cy-CA displays a remarkable fluorescence off-on transition at 720 nm, achieving a detection limit of 20 ng/mL. The incorporation of cholic acid group into Cy-CA has notably enhanced its ability to target intestinal cells precisely. This modification has demonstrated the specific detection of NTR in living cells, making Cy-CA a potent tool for studying the degree of cellular hypoxia in intestinal cells. In addition, the probe is able to monitor changes in NTR levels in mice with dextran sulphate sodium (DSS)-induced IBD. As far as we know, this represents the novel fluorescent probe designed for both intestinal targeting and NTR detection. As a result, Cy-CA holds the promise as a valuable diagnostic tool, offering a novel approach to monitor NTR activity and diagnose IBD with high specificity and sensitivity.