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

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.