L-Arginine-Modified Selenium Nanozymes Targeting M1 Macrophages for Oral Treatment of Ulcerative Colitis

Ulcerative colitis (UC) involves persistent inflammation in the colon and rectum, with excessive reactive oxygen species (ROS) accumulation. This ROS buildup damages colonic epithelial cells and disrupts intestinal flora, worsening disease progression. Current antioxidant therapies are limited due to their instability in the gut and lack of targeting, hindering precise intervention at the lesion site. This study prepares an L-Arginine-modified selenium nanozyme (Se-CA) for the targeted oral treatment of UC. Se-CA specifically targets M1-type macrophages at sites of inflammation by binding to cationic amino acid transporter protein 2 on the surface of M1-type macrophages. In vitro studies show that Se-CA scavenges reactive ROS and reactive nitrogen species (RNS) in artificial gastric acid and intestinal fluids, and inhibits iron death in intestinal epithelial cells. In mice model of ulcerative colitis, oral administration of Se-CA is effective in the treatment of colitis through its anti-inflammatory and antioxidant properties, inhibition of iron death and regulation of intestinal flora. In conclusion, this work provides new insights into the targeted oral treatment of UC.