Wang Liying, Gao Zerui, Tian Mengxiang, Liu Li, Xie Jinyan, Chen Muxiong, Huang Zihao, Dong Bingzhi, Li Weiqi, Shi Liang, Tong Yifan, Xu Hongxia, Shen Bo, Cen Dong, Yu Hong, Yu Xin
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, People's Republic of China.
Zhejiang Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, People's Republic of China.
Nano Lett. 2025 May 28;25(21):8644-8654. doi: 10.1021/acs.nanolett.5c01495. Epub 2025 May 14.
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.
重症急性胰腺炎（SAP）是一种危及生命的疾病，其特征是活性氧（ROS）产生过多和线粒体功能受损，这是由自噬通量破坏所致。目前针对SAP的临床治疗未能全面解决该病症，治疗仅针对单一发病机制。在此，我们报告一种创新的酸响应仿生纳米酶。该系统具有中空普鲁士蓝（PB）核心，作为ROS清除剂封装在多孔ZIF-8壳内，能够有效递送激活自噬通量的雷公藤红素。包裹在巨噬细胞膜中，该系统选择性地靶向炎症胰腺组织，并易于被胰腺腺泡细胞内化。这种双重清除机制在三种不同的SAP小鼠模型中有效降低炎症细胞因子水平并恢复线粒体稳态。总体而言，本研究提出了一种有前景的协同策略，用于对受损线粒体和ROS进行双重清除，为SAP的治疗提供了一种新的治疗方法。
