An ROS/DAMP dual-scavenging nanomedicine for normalizing macrophage polarization and microbiome in colitis

Treatment for ulcerative colitis (UC) remains a clinical challenge as conventional approaches mostly use immunosuppressive agents to ameliorate pro-inflammatory colonic immune responses, which often induce severe side effects. Herein, we report the development of zeolitic imidazolate framework coated cerium dioxide core-shell nanoparticles for drug-free UC therapy. In compliance with clinical standards, the nanomedicine could be administered through oral or enema route for treating UC. The nanomedicine could cooperatively scavenge the excessive reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) in intestinal macrophages and promote their repolarization into anti-inflammatory M2 phenotypes, thus normalizing the pro-inflammatory immune composition in inflamed colons. Owing to the anti-inflammatory performance, the nanoparticles also successfully abolished the UC-related gut-microbiota disorders and restored the normal mucosal structures and functions, thus completely reversing the UC-induced intestinal damage. Our work provides a potential candidate for drug-free UC treatment in the clinics.