Biocompatible carbon dots nanozymes as ROS/RNS modulators for ulcerative colitis alleviation by comprehensively orchestrating intestinal homeostasis

Abstract

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), is characterized by the presence of chronic, nonspecific, and recurring inflammation in the intestine. Current therapies are insufficient in addressing the effective modulation of the intestinal oxidative stress-inflammation cycle, the repair of the intestinal mechanical barrier, and the regulation of gut microbiota and metabolites. There is a need for a comprehensive approach to orchestrate intestinal homeostasis more effectively. For this purpose, biocompatible antioxidant carbon dots nanozymes (GH-CDs) were synthesized based on glucose and D-histidine using a microwave-assisted method for the systematic management of intestinal inflammation. It was demonstrated that GH-CDs possessed excellent reactive oxygen/nitrogen species (ROS/RNS) scavenging capacities, thus modulating oxidative stress-induced damage and mitigating inflammation by inhibiting the TNF, MAPK, PI3K-Akt, NF-κB, and JAK-STAT signaling pathways. For in vivo experiments, GH-CDs have demonstrated both protective and therapeutic effects in mitigating colitis by reducing ROS levels, decreasing the infiltration of M1-type macrophages, suppressing the release of pro-inflammatory cytokines, and repairing intestinal mechanical and chemical barriers. Importantly, GH-CDs also influenced the gut microbiome to achieve a more beneficial state, which was accomplished by enhancing bacterial diversity and altering the microbial composition towards an anti-inflammatory type. Additionally, GH-CDs supported the biosynthesis of secondary bile acids and isoflavonoids. In conclusion, with excellent biocompatibility, GH-CDs will be a promising strategy for UC by comprehensively orchestrating intestinal homeostasis.