DNA Nanopatch-Specific\nModification of Probiotics\nfor Ultrasound-Triggered Inflammatory Bowel Disease Therapy

Probiotics offer promising results for treating inflammatory\nbowel\ndisease, yet precision therapy remains challenging, particularly in\nmanipulating probiotics spatially and temporally and shielding them\nfrom oxidative stress. To address these limitations, herein we synthesized\nbacteria-specific DNA nanopatches to modify ultrasound-triggered engineered Escherichia coli Nissle 1917. These probiotics produced\nthe anti-inflammatory cytokine interleukin-10 when stimulated by ultrasound\nand were fortified with DNPs for oxidative stress resistance. The\nDNPs were composed of rectangular DNA origami nanosheets with reactive\noxygen species’ scavenging ability and bacterial targeting\nligands of maltodextrin molecules. We systematically demonstrated\nthat the DNPs could selectively attach to bacterial surface but not\nmammalian cell surface via the maltodextrin transporter pathway. To\nfurther enhance the bioavailability of engineered probiotics in the\ngastrointestinal tract, we employed a self-assembly strategy to encapsulate\nthem using chitosan and sodium alginate. In a murine model of ulcerative\ncolitis, this system significantly improved the gut barrier integrity\nand reduced inflammation. Our results indicate that this DNA nanopatch-bacteria\nsystem holds substantial promise for mitigating oxidative stress,\ncorrecting microbiota dysbiosis, and enhancing the intestinal barrier\nfunction in colitis.