In vivo assessing colitis severity by topical administration of fluorescent probe against neutrophils

Inflammatory bowel disease has become a global burden given its high incidence and refractory to medical treatment. Improved diagnostic strategies to monitor disease activity more accurately are necessary to conduct and evaluate medical treatment. High level of neutrophil infiltration in colon is associated with poor prognosis and enhanced risk of developing colitis-associated cancer. Herein, to accurately monitor neutrophil levels in colitis condition, we designed and constructed a specific probe (CPM), consisting of a neutrophil formyl peptide receptor targeting group (cFLFLFK), a short PEG linker and a near-infrared fluorescent dye. CPM selectively identified neutrophils in vitro and preferentially recognized neutrophils in vivo with enhanced targeting ability and biodistribution property. After verified the ability to target activated neutrophils, CPM was used to detect neutrophils in experimental colitis by systemic and topical administration. Compared to systemic administration, topical administration of CPM allows lower dosage, higher target-to-background ratio and longer duration of effective monitoring. More importantly, we used CPM to assess neutrophil levels in the course of colitis development. The fluorescence intensity of CPM increased along with colitis progression. Additionally, CPM was used to detected neutrophil levels in colitis-associated cancer and enhanced neutrophil infiltration in the tumor sites was detected. In conclusion, the probe CPM is a promising tool for in vivo improved diagnosis of colitis severity by monitoring the extent of neutrophil infiltration.