“Turn-On” Nanoprobe for Stage-Differential Imaging of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal disorder with increasing incidence globally. Accurate assessment of its progression is essential for clinical management but remains challenging. Herein, we report a GzmA-activatable near-infrared (NIR) nanoprobe IR780 NP@S100 for stage-differential imaging of DSS-induced acute colitis. A molecular precursor, Cys(StBu)-Gly-Phe-Phe-Arg-Lys(IR780)-CBT (IR780-CBT), was designed to prepare the fluorescence-quenched nanoparticle IR780 NP in vitro with a CBT-Cys click reaction. In the presence of granzyme A (GzmA), a serine protease associated with IBD, IR780 NP was disassembled to turn the NIR fluorescence "On". For in vivo application, IR780 NP was encapsulated in Eudragit S100 to afford IR780 NP@S100 which stabilized the nanoparticle in the stomach but specifically released it in the colon. For IBD mouse models at an early stage (day 4) with higher expression of GzmA, IR780 NP showed higher "On" fluorescence in their colons. However, it showed lower "On" fluorescence in the colons of IBD mice at the late stage (day 8). Moreover, IR780 NP enabled fecal fluorescence analysis of IBD, providing a complementary noninvasive readout for monitoring colitis progression. We anticipate that IR780 NP@S100 can be applied for stage-differential imaging of acute colitis in the clinic in the near future.