<i>Shewanella</i> ‐Augmented Cerium Oxide Nanoclusters With Superior Antioxidant Activity for Enhanced Radioprotection of Intestine

ABSTRACT Developing oral radioprotectants for radiation‐induced gastrointestinal syndrome (RIGS) is hindered by the non‐renewable catalytic capacity of conventional antioxidants and the harsh gastrointestinal biological barriers. Herein, we developed a self‐regenerating bio‐hybrid nanozyme, SW@CeO 2 , by in situ growth of cerium oxide on electroactive Shewanella oneidensis (SW). Uniquely, this system exploits bacterial extracellular electron transfer (EET) to continuously fuel the reversible Ce 3+ /Ce 4+ redox cycle, thereby sustaining the catalytic scavenging of radiation‐induced reactive oxygen species (ROS). Following oral administration, SW@CeO 2 demonstrates exceptional gastrointestinal stability, favorable biodistribution, and efficient intestinal colonization. In a lethal irradiation mouse model, the bio‐hybrid effectively mitigates oxidative stress, preserves intestinal barrier integrity, and reshapes the gut microbiota by enriching beneficial taxa such as Lactobacillaceae . Remarkably, SW@CeO 2 increases the survival rate from 0% to 80%. This study presents a novel paradigm of harnessing microbial electron transport to sustain inorganic nanozyme activity, providing a robust and translatable solution for radioprotection.