Shewanella-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@CeO₂, 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 Ce³⁺/Ce⁴⁺ redox cycle, thereby sustaining the catalytic scavenging of radiation-induced reactive oxygen species (ROS). Following oral administration, SW@CeO₂ 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@CeO₂ 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.