Bi2O2Se nanosheets coated with rosmarinic acid for colon-targeted treatment of inflammatory bowel disease

The accumulation of reactive oxygen species (ROS) within colonic tissue represents a critical factor in the pathogenesis of inflammatory bowel disease (IBD). The application of antioxidant therapy utilizing artificial nanozymes has emerged as an effective strategy for the management of IBD. Nevertheless, current nanozymes exhibit limitations in stability, tissue compatibility, and systemic toxicity, which constrain their applicability within the biomedical domain. Herein, we designed a biocompatible colon-targeted integrated therapeutic system (BiOSe-RA@FP), the core of which is Bi 2 O 2 Se (BiOSe) nanosheets encapsulating natural plant rosmarinic acid (RA), enclosed within pH-responsive enteric hydrogel microspheres (FP). This system ensures targeted delivery of BiOSe-RA to the inflamed colon and prolongs its local retention time. BiOSe-RA fully exerts the activities of superoxide dismutase (SOD) and catalase (CAT) in the colon, effectively removing ROS (·OH, ·O 2 − , and H 2 O 2 ). Concurrently, BiOSe-RA exerts excellent anti-inflammatory activities in the colon, which could inhibit the secretion of inflammatory factors, and induce macrophages to polarize the M2 type. The ultimate effect is to preserve the integrity of the intestinal epithelial mucosal barrier and restore microbial homeostasis in the colon by mitigating intestinal oxidative stress and ameliorating the inflammatory microenvironment. The constructed BiOSe-RA@FP could regulate intestinal microbial community disorders, providing a safe and effective new solution for the treatment of IBD.