Development of Akkermansia Muciniphila Membrane‐Coated Mesoporous Silica Nanoparticles with a Cerium Oxide Core for Inflammatory Bowel Disease Treatment

This study introduces an innovative strategy that integrates functional commensal probiotic-derived outer membranes and mesoporous silica nanoparticles containing a cerium dioxide core, renowned for its antioxidant properties. This assembly is designed to reliably reach the lesion sites and exert its therapeutic effects, thereby effectively alleviating the symptoms of inflammatory bowel disease.

Abstract

While convenient for patient compliance, the efficacy of oral treatments for inflammatory bowel disease (IBD) is often compromised by the dynamic and harsh chemical environment of the gastrointestinal tract, presenting challenges for effective therapeutic management. The pathological complexity of IBD frequently involves multiple factors such as oxidative stress, immune dysregulation, gut microbiome abnormality, and inadequate drug bioavailability, among others. To address these challenges, this project develops an oral nanomedicine platform based on mesoporous silica nanoparticles with a cerium oxide core, further coated with an outer membrane (OM) derived from Akkermansia muciniphila (Akk), a beneficial bacteria naturally present in the human gut. This novel nanocomplex, termed “OM-CeMeso,” is evaluated for its enhanced stability, reactive oxygen species (ROS) scavenging capacity, and ability to restore microbiota homeostasis. This project demonstrates that the silica-based nanomaterials’ acid-resistant yet base-degradable properties significantly improved stability in a murine IBD model. The incorporation of cerium oxide nanoparticles (CeO₂ NPs) added further benefits by enhancing ROS scavenging. Notably, the Akk-derived OM coat also increases the diversity and abundance of beneficial gut microbiota. These complementary and integrated functions lead to significant symptom alleviation in murine IBD models while avoiding any unwanted toxicity.