Nucleic Acid-Functionalized Gold Nanorods Modulate Inflammation and Dysregulated Intestinal Barriers for Treatment of Ulcerative Colitis

Traditional oral treatments for ulcerative colitis (UC) face marked limitations including their single therapeutic effect, potential off-target interactions, and toxic side effects. In this study, we present nucleic acid-functionalized gold nanorods (NAF AuNRs), a biocompatible nanomaterial designed for the oral treatment of dextran sulfate sodium (DSS)-induced colitis. The NAF AuNRs alleviate immune responses by inhibiting pro-inflammatory macrophages and enhancing the expression of barrier proteins in intestinal epithelial cells. Due to the negatively charged nucleic acid shell, NAF AuNRs preferentially target anionic, inflamed colon tissues upon oral administration, reducing pro-inflammatory cytokine levels and promoting the recovery of intestinal barrier in DSS-induced colitis mice. Collectively, these findings suggest that NAF AuNRs represent an innovative and promising therapeutic approach for UC management, offering novel insights into the application of nucleic acid-functionalized nanomaterials.