An Oral H<sub>2</sub>S Responsive Cu<sub>5.4</sub>O Nanozyme Platform with Strong ROS/H<sub>2</sub>S Scavenging Capacity\nfor the Treatment of Colitis

Inflammatory bowel disease involves excess reactive oxygen\nspecies\n(ROS) and hydrogen sulfide (H<sub>2</sub>S) at inflammatory sites.\nNanozyme-mediated ROS and H<sub>2</sub>S scavenging therapy is promising\nfor colitis treatment. Here, we synthesized a multiple ROS scavenging\nCu<sub>5.4</sub>O nanoparticle and first explored its H<sub>2</sub>S scavenging capacity. Chitosan oligosaccharide modified with alpha-lipoic\nacid was coated on the nanoparticles to further enhance the H<sub>2</sub>S scavenging capacity. Furthermore, calcium alginate was coated\non the surface to develop an oral nanoplatform (Cu<sub>5.4</sub>O@SAG)\npossessing dual-pH/H<sub>2</sub>S-responsive release characteristics.\nImportantly, Cu<sub>5.4</sub>O@SAG exhibited enrichment at the colonic\ninflammation site and relieved the inflammatory index, containing\nthe recovery of colon length, spleen index, liver index, and body\nweight, as well as inflammatory cell infiltration. In vivo and in\nvitro experiments revealed the dual ROS and H<sub>2</sub>S scavenging\ncapacities of the nanoplatform. Additionally, Cu<sub>5.4</sub>O@SAG\nregulated tight junctions, mucus layers, and gut microbiota, which\nwas accompanied by the downregulation of inflammatory cytokines. Notably,\nCu<sub>5.4</sub>O@SAG also had excellent biocompatibility. In conclusion,\nthis oral multiple-scavenging nanozyme platform provides a new and\nsafe paradigm for the development of nanozymes for colitis treatment.