Oral administration of nanozyme-armed probiotic Escherichia coli Nissle 1917 with ROS scavenging for inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) represents a group of chronic, non-specific gastrointestinal disorders characterized by pathological overproduction of reactive oxygen species (ROS). Current therapeutic interventions, including conventional drugs and oral probiotics, are frequently limited by their vulnerability to the harsh gastrointestinal environment. To address these challenges, we have developed a novel engineered bacterium, designated as CeO₂@EcN-L, through the integration of cerium oxide nanozymes (CeO₂) with the probiotic strain Escherichia coli Nissle 1917 (EcN), followed by encapsulation with a pH-responsive anionic copolymer composed of methacrylic acid and ethyl acrylate (Eudragit L100–55). The negatively charged surface of the Eudragit L100–55 coating enables CeO₂@EcN-L to not only selectively adhere to positively charged inflamed colon tissues through electrostatic interactions but also achieve sustained release of therapeutic agents throughout the gastrointestinal tract. Upon accumulation in the inflamed colon, the CeO₂ component demonstrates dual enzymatic activities, mimicking both catalase (CAT) and superoxide dismutase (SOD), which collectively facilitate efficient ROS scavenging and subsequent inflammation alleviation. In a dextran sulfate sodium (DSS)-induced murine IBD model, CeO₂@EcN-L demonstrate remarkable anti-inflammatory efficacy and significantly restore gut microbiota homeostasis. This study establishes a novel, safe, and effective therapeutic strategy for IBD treatment, offering promising potential for clinical translation.