A quercetin-modified bifunctional system for efficient acute pancreatitis treatment via inhibiting oxidative stress and modulating inflammation.

Acute pancreatitis (AP), a life-threatening inflammatory disorder characterized by excessive oxidative stress and macrophage-driven inflammation, remains a significant clinical challenge due to limited therapeutic options. Herein, for the first time, we report a novel therapeutic strategy for AP by developing a bifunctional nanohybrid system, denoted as CeOx@Que., which combines a ceria-based antioxidant nanozyme with the immunomodulatory agent quercetin (Que). This unique system possesses broad-spectrum enzyme-mimetic antioxidant activity, enabling efficient scavenging of reactive oxygen species (ROS) within pancreatic tissues. Simultaneously, it modulates the inflammatory microenvironment by promoting macrophage polarization toward the anti-inflammatory M2 phenotype through the synergistic effects of its antioxidant properties and the intrinsic pharmacological activities of Que. As a result, our bifunctional agent potently manages the progression of AP by alleviating oxidative stress and local inflammation at the disease site. Furthermore, by preventing the dissemination of pro-inflammatory cytokines from the pancreatic site into the circulation, it effectively averts the onset of systemic inflammatory responses and remote organ failure. This study highlights a promising new approach for the treatment of AP and underscores the potential of multifunctional nanozymes in managing inflammatory diseases.