CO-Releasing Polyoxometalates Nanozyme with Gut Mucosal Immunity and Microbiota Homeostasis Remodeling Effects for...

Area of Science:

• Gastroenterology
• Nanomedicine
• Immunology

Background:

• Inflammatory bowel disease (IBD) pathogenesis involves intestinal epithelial barrier disruption, immune dysregulation, and microbial imbalances.
• Current IBD treatments face challenges in efficacy and side effects.

Purpose of the Study:

• To develop and evaluate a novel CO-releasing polyoxometalates (POMs) nanozyme (PMC) for IBD treatment.
• To investigate PMC's therapeutic mechanisms, including barrier repair, antioxidant, anti-inflammatory, and immunomodulatory effects.

Main Methods:

• Synthesis of PMC by coordinating pentacarbonyl manganese bromide with molybdenum-based POM nanoclusters.
• In vitro and in vivo studies using cell models and animal models of ulcerative colitis.
• Assessment of intestinal barrier integrity, reactive oxygen species (ROS) scavenging, CO release, gut microbiota composition (16S rRNA sequencing), and immune cell profiles (single-cell RNA sequencing).

Main Results:

• PMC demonstrated targeted accumulation at IBD-affected sites, efficient ROS scavenging, and responsive CO release.
• PMC significantly repaired the intestinal barrier, exhibiting potent antioxidant and anti-inflammatory properties.
• PMC remodeled gut microbiota, reduced pro-inflammatory M1 macrophages, and suppressed inflammatory pathways.
• PMC promoted M2 macrophage and intestinal stem cell populations, activating VEGF and NOTCH signaling pathways.

Conclusions:

• PMC is a promising multifunctional therapeutic agent for IBD, effectively restoring intestinal barrier function and immune homeostasis.
• The nanozyme's ability to modulate gut microbiota and promote tissue repair highlights its therapeutic potential for ulcerative colitis.