HClO‐Activated Near‐Infrared Chemiluminescent Probes with a Malononitrile Group for In‐Vivo Imaging

Abstract Chemiluminescence (CL) imaging has emerged as a powerful approach to molecular imaging that allows exceptional sensitivity with virtually no background interference because of its unique capacity to emit photons without an external excitation source. Despite its high potential, the application of this nascent technique faces challenges because the current chemiluminescent agents have limited reactive sites, require complex synthesis, are insufficiently bright, and lack near‐infrared emission. Herein, a series of HClO‐activated chemiluminescent probes that exhibit robust near‐infrared emission are studied. Specifically engineered to respond to HClO, a known biomarker of acute inflammation, these probes achieve high‐contrast in vivo imaging by eliminating the need for constant external excitation. Comprehensive experimental and theoretical investigations demonstrate that the CL of the probes depends on the reactivity of the vinylene bonds, following a concerted decomposition of the oxidized chemiluminescent molecule. The application of these chemiluminescent nanoparticles in vivo facilitates high‐contrast imaging of acute inflammation, providing real‐time, high‐contrast visualization of inflammatory conditions. This advancement signifies a leap forward for chemiluminescent nanoplatforms in biomedical imaging and expands the available methodologies in this field.