Abstract

Nanotechnology has significantly facilitated the diagnosis and therapy of inflammatory bowel disease (IBD). To obtain better therapeutic efficacy, a nanoplatform built from polysaccharides and metal-phenolic networks (MPN) is developed here to enhance retention in the damaged intestinal region and modulate systemic immunological status in IBD models. Polysaccharides from tragacanth gum (GUM) are coordinated with iron and further interact with shikonin (Shik) to obtain a nanocomposite named Shik-Fe@GUM. Shik-Fe@GUM demonstrates strong and persistent accumulation in the inflamed intestinal region, which is validated in clinical specimens from IBD patients, cocultured cellular models, and living animals. Shik-Fe@GUM served as a strong scavenger for reactive oxygen or nitrogen species in inflamed tissues or cells, and alleviated local and systemic inflammatory status by cytokine downregulation. In addition, Shik-Fe@GUM restored the functions of damaged colonic barriers and mitigate disease activity index. The working mechanisms of Shik-Fe@GUM are also explored and genetic sequencing results revealed that Shik-Fe@GUM imposed its treatment effect from attenuating major inflammatory pathways. In particular, Shik-Fe@GUM can modulate IL-17RA relevant cell signaling and reduce the recruitment of T_h17 cells (T helper cell 17). This polysaccharide-metal-functional molecule hybrid strategy can be broadly applicable to other IBD drugs and enhance their therapeutic index in patients.