Enteric-gated nano–probiotic living nanozyme for gut-directed redox–mitochondrial protection in cisplatin-induced acute kidney injury

Abstract

Oral nano-biohybrid therapeutics provide opportunities for gut–organ axis intervention, but gastrointestinal transit often compromises both probiotic viability and nanozyme activity. Here, we developed CeO 2 @LP@EL, an enteric-gated nano–probiotic living nanozyme constructed by decorating cerium oxide nanozymes onto viable Lactobacillus paracasei and enclosing the hybrid within an EL100-55 enteric layer. This hierarchical architecture preserved hybrid integrity, viable bacterial survival, redox-protective activity, and epithelial adhesion after simulated gastrointestinal processing. In intestinal epithelial cells, CeO 2 @LP@EL reduced oxidative stress and supported antioxidant homeostasis. In cisplatin-induced acute kidney injury, oral CeO 2 @LP@EL attenuated renal dysfunction and tubular damage, accompanied by intestinal barrier repair, reduced endotoxemia and inflammation, oxidative stress suppression, gut microbiota remodeling, mitochondrial preservation, and recovery-associated renal transcriptional changes. These findings identify enteric gating as a practical nano-biohybrid design principle for coordinating probiotic viability and nanozyme-associated redox regulation in gut-directed renoprotection. CeO 2 @LP@EL integrates enteric gating, nanoceria redox buffering, and probiotic gut regulation to enable gut-directed renoprotection against cisplatin-induced AKI.