Chemiluminescent Probes with Long‐Lasting High Brightness for In Vivo Imaging of Neutrophils

Abstract Real‐time optical imaging of immune cells can contribute to understanding their pathophysiological roles, which still remains challenging. Current sensitive chemiluminophores have issues of short half‐lives and low brightness, limiting their ability for in vivo longitudinal monitoring of immunological processes. To tackle these issues, we report benzoazole‐phenoxyl‐dioxetane (BAPD)‐based chemiluminophores with intramolecular hydrogen bonding for in vivo imaging of neutrophils. Compared with the classical counterpart, chemiluminescence half‐lives and brightness of BAPDs in the aqueous solution are increased by ∼ 33‐ and 8.2‐fold, respectively. Based on the BAPD scaffold, a neutrophil elastase‐responsive chemiluminescent probe is developed for real‐time imaging of neutrophils in peritonitis and psoriasis mouse models. Our study provides an intramolecular hydrogen bonding molecular design for improving the performance of chemiluminophores in advanced imaging applications.