pH-responsive phytochemical hydrogel loaded with antioxidant nanozymes for synergistic ROS scavenging and targeted inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) remains a therapeutic challenge due to its complex pathophysiology involving oxidative stress and chronic inflammation. Here, we developed a multifunctional hydrogel system (CeO2@Rh-gel) integrating rhein, a natural anti-inflammatory agent, and CeO2 NPs with ROS scavenging nanozyme activity for controlled release IBD therapy. The CeO2@Rh-gel was fabricated through self-assembly, forming a pH-responsive network that protected payloads in the stomach while enabling controlled release in the inflamed colon. In vitro, CeO2@Rh-gel exhibited synergistic antioxidant effects, mimicking SOD and CAT to eliminate ROS, while suppressing pro-inflammatory cytokines in LPS-stimulated macrophages. In a DSS-induced murine colitis model, oral CeO2@Rh-gel significantly alleviated disease severity, as evidenced by reduced weight loss, normalized colon length, and improved histopathology. Mechanistically, the hydrogel restored redox homeostasis and attenuated systemic inflammation. By combining ROS scavenging, anti-inflammatory action, and controllable delivery, CeO2@Rh-gel offers a promising dual-functional strategy for precision IBD therapy.