A DNA Nanopatch-Bacteriophage System Targeting Streptococcus Gallolyticus for Inflammatory Bowel Disease Treatment and Colorectal Cancer Prevention

Abstract

Persistent inflammation in inflammatory bowel disease (IBD) increases Streptococcus gallolyticus (Sg) colonization, increasing the risk of colorectal cancer progression via the Sg-activated cyclooxygenase-2 (COX-2) pathway and β-catenin upregulation. This study presents Sg-specific bacteriophages modified with DNA nanopatches (DNPs@P) designed to treat IBD and prevent Sg-induced malignancy. The DNPs are composed of DNA origami nanosheets and phage capture strands. The DNPs scavenge reactive oxygen species, enhancing the therapeutic efficacy of the phages while targeting and lysing pathogenic bacteria. Coating with an enteric polymer, DNPs@P ensures effective delivery in the gastrointestinal tract. These findings demonstrate significant restoration of colonic length, reduced inflammation, and improved gut microbiota diversity compared with current clinical treatments. Additionally, DNPs@P effectively prevents colonic tumourigenesis in mouse models. This approach presents a promising strategy for treating gastrointestinal diseases by remodeling the gut microenvironment, addressing a critical gap in current therapies.