Oral Metal‐Free Melanin Nanozymes for Natural and Durable Targeted Treatment of Inflammatory Bowel Disease (IBD)

Abstract Oral antioxidant nanozymes bring great promise for inflammatory bowel disease (IBD) treatment. To efficiently eliminate reactive oxygen species (ROS), various metal‐based nanozymes have been developed for the treatment of IBD but their practical applications are seriously impaired by unstable ROS‐eliminating properties and potential metal ion leakage in the digestive tract. Here, the authors for the first time propose metal‐free melanin nanozymes (MeNPs) with excellent gastrointestinal stability and biocompatibility as a favorable therapy strategy for IBD. Moreover, MeNPs have extremely excellent natural and long‐lasting characteristics of targeting IBD lesions. In view of the dominant role of ROS in IBD, the authors further reveal that oral administration of MeNPs can greatly alleviate the six major pathological features of IBD: oxidative stress, endoplasmic reticulum stress, apoptosis, inflammation, gut barrier disruption, and gut dysbiosis. Overall, this strategy highlights the great clinical application prospects of metal‐free MeNPs via harnessing ROS scavenging at IBD lesions, offering a paradigm for antioxidant nanozyme in IBD or other inflammatory diseases.