Recent advances in antioxidant nanozymes for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) refers to a group of chronic, nonspecific gastrointestinal disorders that impose a significant global health burden. Conventional therapies are frequently hindered by severe off-target toxicities and compromised efficacy within the dynamically changing intestinal microenvironment. Recently, nanozymes have emerged as a revolutionary therapeutic paradigm for IBD, offering potent reactive oxygen species (ROS) scavenging and profound immunoregulatory capabilities. Herein, we summarize the latest advances in nanozyme-based IBD therapies. Firstly, we categorize the diverse nanozyme platforms utilized in IBD therapy, spanning metal-based, metal-organic framework (MOF)-based, organic, and carbon-based materials. Subsequently, we highlight how advanced rational design strategies, including surface modification, electronic structure regulation, defect engineering, and atomic doping, orchestrate complex bio-modulatory effects, encompassing mitochondrial homeostasis restoration, inflammatory signaling pathway modulation, programmed cell death (PCD) intervention, and intestinal barrier regeneration. Furthermore, to overcome biopharmaceutical bottlenecks, we provide an overview of nanozyme-based intelligent delivery platforms tailored for the inflamed gut, covering endogenous/exogenous stimuli-responsive, biomimetic, and microbiota-mediated systems. Finally, we critically evaluate the impending translational challenges and future perspectives of nanozyme-based nanomedicines, providing a rigorous roadmap for the development of spatiotemporally controlled, precision gastroenterology therapies.