Highly Bright Near-Infrared Chemiluminescent Probes for Cancer Imaging and Laparotomy

Near-infrared (NIR) chemiluminescence imaging holds potential for sensitive imaging of cancer due to its low background; however, few NIR chemiluminophores are available, which share the drawback of low chemiluminescence quantum yields (Φ_CL ). Herein, we report the synthesis of NIR chemiluminophores for cancer imaging and laparotomy. Molecular engineering of the electron-withdrawing group at the para-position of the phenol-dioxetane leads to a highly bright NIR chemiluminophore (DPT), showing the Φ_CL (4.6×10^-2  Einstein mol^-1 ) that is 3 to 5-fold higher than existing NIR chemiluminophores. By caging the phenol group of DPT with a cathepsin B (CatB) responsive moiety, an activatable chemiluminescence probe (DPT_CB ) is developed for real-time turn-on detection of deeply buried tumor tissues in living mice. Due to its high brightness, DPT_CB permits accurate chemiluminescence-guided laparotomy.