An Orally Administered CeO2@Montmorillonite Nanozyme Targets Inflammation for Inflammatory Bowel Disease Therapy

Abstract Safe, effective, and convenient administration of therapeutic nanomaterials is one of the greatest difficulties in nanomedicine. To tackle this challenge, a system which couples multi‐enzyme mimicking CeO 2 nanoparticles with clinically approved montmorillonite (MMT) for inflammatory bowel disease (IBD) therapy is reported. CeO 2 exhibits superoxide dismutase‐ and catalase‐like activities, and hydroxyl radical scavenging activity, making it more efficient at scavenging reactive oxygen species (ROS) than non‐catalytic antioxidants while being more stable than free enzymes. In addition, negatively‐charged MMT can be orally administered and specifically adsorbed onto positively‐charged inflamed colon tissue via electrostatic interactions for targeted delivery. When the two are assembled together by in situ growth of CeO 2 onto MMT, the optimized CeO 2 @MMT(1:9) is stable in the stomach for oral delivery, targets the inflamed colon through electrostatic interactions, and reduces inflammation through ROS scavenging, all without any significant systemic exposure as demonstrated by the relief of murine IBD in vivo.