Lighting up intestinal inflammation in situ with a pH-insensitive NIR fluorescent probe

The accurate and sensitive in situ imaging of inflammatory bowel disease (IBD) is critical for the precise diagnosis and treatment of this disease, but it remains a challenge for fluorescent probes because of a more dynamical shift of pH in the intestinal tract than under other physical conditions. To address this issue, we report here that the rational introduction of the ortho-halogen bond at the electron acceptor can regulate the protonation and deprotonation of fluorescent dye, resulting in a pH-insensitive dye (pH 5–12). Therefore, constructing a near-infrared (NIR) probe, 2F-RBH, which effectively avoids this pH effect with a stable fluorescent signal and selectively indicates sites of inflammation in situ, by tracking peroxynitrite (ONOO−) in an acute colitis mouse model. Collectively, our results highlight that 2F-RBH is a promising probe for the imaging of IBD and that our pH-insensitive dye has potentially desirable properties for in vivo bioimaging.