An oral ratiometric NIR-II fluorescent probe for reliable monitoring of gastrointestinal diseases in vivo

Early monitoring of gastrointestinal diseases via orally delivered NIR-II ratiometric fluorescent probes represents a promising noninvasive diagnostic modality, but is challenging due to the limitation of harsh digestive envi-ronment. Here, we report a single-component NIR-II ratiometric molecular nanoprobe (LC-1250 NP) to monitor gastrointestinal disease with high specificity to its biomarker H2O2 via oral administration. LC-1250 NP displays stable fluorescence in the channel of 1250 long-pass (F1250LP) before and after the gastrointestinal disease detection as the reference, while it presents significantly enhanced fluorescence signal in the response channel of 1150 nm short-pass (F1150SP) in diseased gastrointestinal environment due to the intramolecular cyclization of LC-1250 molecules activated by H2O2. The fluorescence ratio (F1150SP/F1250LP) increases linearly with the con-centration of H2O2 with a low detection limit of 20 nM. Therefore, when delivered orally, LC-1250 NP can accurately map the diseased areas and surmount the false-positive interference from biological heterogeneity by NIR-II ratiometric fluorescence imaging, providing sensitive and reliable evaluation for the progress of gastroenteritis.

Automated summary

This study presents a single-component NIR-II ratiometric molecular nanoprobe (LC-1250 NP) for early monitoring of gastrointestinal diseases via oral administration. LC-1250 NP shows stable fluorescence in the 1250 nm long-pass channel before and after disease detection, but exhibits enhanced fluorescence in the 1150 nm short-pass channel in the diseased gastrointestinal environment due to the activation of LC-1250 molecules by H2O2. The ratio of fluorescence signals (F1150SP/F1250LP) linearly increases with the concentration of H2O2, providing accurate mapping of the diseased areas and reliable evaluation for the progress of gastroenteritis.