Development of ellagic acid-derived bismuth MOF for targeted therapy in colitis

Oxidative stress plays a key role in inflammatory diseases like colitis, but traditional antioxidants are limited by poor bioavailability and non-specific actions, reducing their effectiveness. This study seeks to overcome these limitations by creating a targeted nanotherapy that combines natural ellagic acid with bismuth-based metal-organic framework (MOF) chemistry. SU-101, a MOF, was synthesized through the coordination of ellagic acid and bismuth acetate. SU-101, with a rod-like shape and a zeta potential of −38.51 mV, effectively targets inflamed colonic tissue. It shows strong radical scavenging and SOD/CAT-mimetic activities, providing dual therapeutic benefits. At 5 mg/kg orally, SU-101 outperforms 5-aminosalicylic acid (5-ASA) by reducing weight loss, lowering pro-inflammatory cytokines (IL-6, TNF-α), restoring intestinal barrier proteins, and altering gut microbiota and arginine metabolism. As the ellagic acid-derived bismuth MOF, SU-101 offers precise, multi-level treatment for oxidative inflammation, with promising oral bioavailability and microbiome remodeling potential for inflammatory bowel disease therapy.