Ca/Fe-Based Nanozymes Relieve Severe Acute Pancreatitis by Ferroptosis Regulation and Reactive Oxygen Species Scavenging

Severe acute pancreatitis (SAP) is a serious inflammatory disease that is often associated with high mortality rate. It tends to trigger a cascade of systemic inflammation that causes damage to multiple organs, such as the lungs and kidneys. Currently, there is no effective treatment plan to reverse the progress of SAP. The occurrence and development of SAP are associated with oxidative stress (OS) and ferroptosis. In this study, the Ca/Fe-based nanozymes are used as multi-enzyme simulants, which can effectively remove the reactive oxygen species and regulate ferroptosis to prevent and treat SAP. Notably, we make two trials for prevention and treatment of SAP. Under the condition of good biocompatibility, the Ca/Fe-based nanozymes effectively reduce the levels of serum pancreatitis-related biomarkers and inflammatory factors which involved in local and systemic inflammatory response. Moreover, the Ca/Fe nanozymes significantly increase the level of ferroptosis regulator of glutathione peroxidase 4 (GPx4) and ferritin heavy chain 1 (FTH1) in pancreas. These results demonstrate that the Ca/Fe-based nanozymes not only alleviate SAP but also mitigate subsequent multi-organ damage, thus providing an effective strategy of Ca/Fe nanozymes for treating SAP-related disorders in clinical research.