A Charge‐Adhesive Targeted DNA Gel Bandage for the Precision Treatment of Inflammatory Bowel Disease

The exacerbation and recurrence of inflammatory bowel disease (IBD) are closely related to the overactivation of the immune system and the destruction of the intestinal mucosa. Current small-molecule and biopharmaceutical therapies for IBD are often limited by off-target effects, low bioavailability, and poor treatment outcomes, leading to systemic side effects and severe complications. To address these challenges, DNA gel bandage (DNAgb) designed to block immune cell homing and inhibit inflammatory responses are proposed. DNAgb is a negatively charged "sticky excipient" formed by a rolling circle amplification production hydrogel and an integrin α4 aptamer (ApITGA4) -guided tetrahedral DNA nanostructure. This unique design enables dual-specific localization to inflamed mucosa through electrostatic interactions and ApITGA4-mediated affinity targeting. Our studies have demonstrated that DNAgb exhibits precise targeting, superior stability, and robust anti-inflammatory efficacy. It effectively inhibits activation of the NF-κB signaling pathway, decreases the secretion of inflammatory factors and reshapes the immune microenvironment. Transcriptome analysis further reveals the underlying mechanism of DNAgb in IBD therapy, highlighting its role in inflammation repression. Therefore, DNAgb provides a promising strategy for local therapeutic agents that effectively inhibit the inflammatory response and provides a new and effective choice for the treatment of IBD.