Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition

• DOI: 10.1002/advs.202412799
• Publication Date: 2025-01-21T17:12:12Z
• Authors: Yan Yan; Bin Li; Qiuxia Gao; Miao Wu; Hua Ma; Jiawei Bai; Chengtai Ma; Xinyu Xie; Yuan Gong; Lingqi Xu; Xiaoxue Li; Wei Wang; Yanqiu Wu; Jiamei Wang; Huanhuan Wang; Yi Feng; Yunlong Zhang; Peiran Li; Huimin Shi; Fei Ma; Yue Jia; Han Duan; Xinting Fu; Wenying Wang; Liying Zhan; Xianjin Du; Huiting Zhou; Yuhui Liao
• Keywords: parthanatos; Science; Q; broad‐spectrum anti‐inflammation; pH‐responsive capsules; sepsis‐induced intestinal injury; olaparib

Abstract Sepsis is a severe systemic inflammatory syndrome characterized by dysregulated immune response to infection, often leading high mortality rates. The intestine, owing its distinct structure and physiological environment, plays pivotal role in the pathophysiology of sepsis. It functions as “central organ” or “engine” progression sepsis, with intestinal injury exacerbating condition. Despite availability current therapies that offer partial symptom relief, they fall short adequately protecting barrier. In this study, an advanced nanodrug formulation (OLA@MΦ NPs) developed coating macrophage membranes onto polymeric organic nanoparticles encapsulating olaparib. When loaded into pH‐responsive capsules, intestine‐decipher engineered capsule (cp‐OLA@MΦ successfully formulated. Upon oral administration septic mice, these capsules withstand gastric acid release their contents specifically targeting injured tissues. released OLA@MΦ NPs effectively neutralize pro‐inflammatory cytokines via membrane receptors, while olaparib inhibits epithelial parthanatos (a form programmed cell death) suppressing poly(ADP‐ribose) polymerase 1 (PARP1) activation. This strategy significantly reduces bacterial translocation, slows enhances survival thus presenting promising therapeutic approach for sepsis clinical applications.