Engineering Coumarin-Based Afterglow Luminescence Probes for Activatable Imaging Peroxynitrite In Vivo

Afterglow luminescence imaging materials have evolved from inorganic to organic systems, and further from macromolecular polymers to small molecules, highlighting the imperative of developing safe and efficient organic afterglow molecules for bioimaging. However, flexible organic afterglow molecules with well-characterized structure-luminescence intensity relationships for high-contrast activatable imaging remain scarce. Here, we report for the first time that coumarin derivatives exhibit bright afterglow luminescence and reveal that rigidified coumarin structures display stronger emission than their flexible and backbone analogues. Further, we designed MP molecules bearing boronic ester and methylenecyclobutane moieties and integrated them with coumarin to construct the activatable afterglow probe C545-MP NPs. Oxidation of the boronic ester by ONOO^- primes the probe, whereas subsequent irradiation induces coumarin-mediated singlet oxygen generation that reacts with the methylenecyclobutane unit to initiate afterglow emission. By virtue of the elimination of autofluorescence and high activation contrast, C545-MP NPs enable precise assessing therapeutic efficacy of ulcerative colitis and Parkinson's disease.