2. Academic Validation
  3. Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition

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

  • Adv Sci (Weinh). 2025 Jan 21:e2412799. doi: 10.1002/advs.202412799.
Yan Yan 1,  Bin Li 2,  Qiuxia Gao 3,  Miao Wu 1,  Hua Ma 3,  Jiawei Bai 1,  Chengtai Ma 1,  Xinyu Xie 1,  Yuan Gong 4,  Lingqi Xu 4,  Xiaoxue Li 5,  Wei Wang 5,  Yanqiu Wu 5,  Jiamei Wang 3,  Huanhuan Wang 3,  Yi Feng 5,  Yunlong Zhang 1,  Peiran Li 6,  Huimin Shi 5,  Fei Ma 2,  Yue Jia 2,  Han Duan 6,  Xinting Fu 6,  Wenying Wang 3,  Liying Zhan 1,  Xianjin Du 1,  Huiting Zhou 4,  Yuhui Liao 2 3
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 2 School of Inspection, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
  • 3 Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
  • 4 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215025, China.
  • 5 Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, 510091, China.
  • 6 Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
PMID: 39836501 DOI: 10.1002/advs.202412799
Abstract

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

Keywords

broad‐spectrum anti‐inflammation; olaparib; pH‐responsive capsules; parthanatos; sepsis‐induced intestinal injury.

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