A Nanosystem Alleviates Severe Acute Pancreatitis via Reactive Oxygen Species Scavenging and Enhancing Mitochondrial Autophagy.

Abstract

Severe acute pancreatitis (SAP) is a life-threatening condition characterized by excessive reactive oxygen species (ROS) production and impaired mitochondrial function, resulting from disrupted autophagic flux. Current clinical treatment for SAP fails to address the condition comprehensively, with the treatment targeting only a single pathogenesis. Herein, we report an innovative acid-responsive biomimetic nanozyme. This system features a hollow Prussian blue (PB) core, serving as an ROS scavenger encapsulated within a porous ZIF-8 shell, enabling the efficient delivery of celastrol that activates autophagic flux. Encased in a macrophage membrane, this system selectively targets inflamed pancreatic tissues and is readily internalized by pancreatic acinar cells. This dual-scavenging mechanism effectively attenuates inflammatory cytokine levels and restores mitochondrial homeostasis in three distinct SAP mouse models. Overall, this study presents a promising synergistic strategy for the dual scavenging of damaged mitochondria and ROS, offering a novel therapeutic approach to the treatment of SAP.