Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.
Yan Yan: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Bin Li: School of Inspection, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. ORCID
Qiuxia Gao: Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
Miao Wu: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Hua Ma: Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
Jiawei Bai: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Chengtai Ma: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Xinyu Xie: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Yuan Gong: Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215025, China.
Lingqi Xu: Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215025, China.
Xiaoxue Li: Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, 510091, China.
Wei Wang: Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, 510091, China.
Yanqiu Wu: Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, 510091, China.
Jiamei Wang: Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
Huanhuan Wang: Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
Yi Feng: Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, 510091, China.
Yunlong Zhang: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Peiran Li: Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Huimin Shi: Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, 510091, China.
Fei Ma: School of Inspection, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Yue Jia: School of Inspection, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Han Duan: Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Xinting Fu: Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Wenying Wang: Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China.
Liying Zhan: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Xianjin Du: Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China. ORCID
Huiting Zhou: Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215025, China.
Yuhui Liao: School of Inspection, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. ORCID
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@M�� 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@M�� 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@M�� 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.
