DNA Nanostructures Treat Inflammatory Bowel Disease through ROS Scavenging and Gut Microbiota Modulation

Abstract Inflammatory bowel disease (IBD) encompasses a collection of chronic inflammatory conditions impacting the gastrointestinal tract, with a discernible global rise in prevalence and severity. The overabundance of reactive oxygen species (ROS) in the intestinal environment leads disruption of local redox homeostasis, and perturbation of the gut microbiota, exacerbating IBD. Consequently, mitigating excess ROS and preserving gut microbiota homeostasis have emerged as effective approaches for IBD management. In this study, a triangular DNA origami nanostructure loaded with siRNA targeting tumor necrosis factor α (^siTNF‐αtDON) is introduced for this purpose. This nanostructure demonstrates efficacy in eliminating ROS within cells closely associated with IBD, diminishing inflammation, and ameliorating disorders in gut microbiota, as evidenced in an IBD mouse model. Furthermore, this investigation demonstrates the effects of ^siTNF‐αtDON on related inflammatory signaling pathways, including NF‐κB, MAPK/ERK and Keap1/Nrf2. Collectively, this study offers insights into the potential utilization of DNA nanostructures as antioxidants and gut microbiota modulators, presenting promising avenues for the IBD treatment.