Selective Fluorescence Imaging and Cascade Catalytic Therapy of Inflammatory Diseases Enabled by Selenium Engineered Carbon Dots

ABSTRACT Inflammatory diseases are characterized by myeloperoxidase (MPO)‐catalyzed production of HClO, a promising diagnostic biomarker. However, current HClO probes suffer from poor selectivity, and an absence of therapeutic function. Inspired by the structure of glutathione peroxidase (GPx), we developed selenium‐doped carbon dots (Se‐CDs) as a biomimetic theranostic nanoplatform. The rational selenium‐engineering strategy confers CDs with exceptional HClO selectivity, enabling fluorescence imaging of MPO‐mediated inflammation, and their organic–inorganic hybrid nature promotes efficient cellular uptake, and combined with ROS‐scavenging activity, contributes to inflammation suppression. In vitro and in vivo studies by an inflammatory bowel disease model validate the capability of Se‐CDs for precise monitoring of HClO dynamics within the inflammatory microenvironment and attenuation of oxidative stress through superoxide dismutase (SOD)–GPx cascade mimicry. Furthermore, the robust ROS‐scavenging capability of Se‐CDs facilitates the gut microbiota restoration via oxidative stress alleviation and intestinal environment recovery. Transcriptomic and molecular analyses corroborate that Se‐CDs alleviate colitis by inhibiting NF‐κB–mediated inflammatory activation and activating the FoxO–SOD2 axis. Collectively, this work establishes Se‐CDs as a versatile nanoplatform that integrates selective HClO imaging with cascade catalytic therapy for the early diagnosis and effective management of inflammatory disorders.