Resistant starch grafted cerium-sulfasalazine infinite coordination polymers synergistically remold intestinal metabolic microenvironment for inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease which is closely related with the overproduced reactive oxygen species (ROS), increased pro-inflammatory cytokines and disordered intestinal microbes. However, current therapeutic methods usually ignored the interrelation among the pathogenesis, and mainly focused on a single factor, inducing clinical outcomes unsatisfied. Herein, biocompatible infinite coordination polymers of drugs (Ce-SASP-RS ICPs) composed of Ce ions, FDA-approved drug sulfasalazine (SASP) and natural ingredient resistant starch (RS) were developed for synergistic treatment of IBD. The proper Ce³⁺/Ce⁴⁺ ratio in Ce-SASP-RS ICPs can endow them with SOD-like activities, POD-like activities and •OH scavenging ability, which guarantee Ce-SASP-RS ICPs to simultaneously kill bacteria and maintain ROS balance through cascade reactions. Owing to the recovered redox balance microenvironment, SASP in Ce-SASP-RS ICPs can better play their anti-inflammatory function. Moreover, benefitting from the recovered metabolic balance of ROS and inflammatory cytokines in colon, resistant starch can also function better in modifying gut microbiota through generating short-chain fatty acids. Collectively, Ce-SASP-RS ICPs can synergistically restore intestinal metabolic microenvironment through modulating redox balance, attenuating inflammation and modifying intestinal flora. Hence, in view of the mutual influences among IBD pathogenesis, this work presents a synergistic intervention approach for effectively treating IBD.