Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition
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 func...
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412799 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yan Yan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c8af76284ec84178812db5c35ddf72ed |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-c8af76284ec84178812db5c35ddf72ed2025-08-20T02:35:40ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202412799Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos InhibitionYan Yan0Bin Li1Qiuxia Gao2Miao Wu3Hua Ma4Jiawei Bai5Chengtai Ma6Xinyu Xie7Yuan Gong8Lingqi Xu9Xiaoxue Li10Wei Wang11Yanqiu Wu12Jiamei Wang13Huanhuan Wang14Yi Feng15Yunlong Zhang16Peiran Li17Huimin Shi18Fei Ma19Yue Jia20Han Duan21Xinting Fu22Wenying Wang23Liying Zhan24Xianjin Du25Huiting Zhou26Yuhui Liao27Department of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaSchool of Inspection Ningxia Medical University Yinchuan Ningxia 750004 ChinaInstitute for Engineering Medicine Kunming Medical University Kunming 650500 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaInstitute for Engineering Medicine Kunming Medical University Kunming 650500 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaInstitute of Pediatric Research Children's Hospital of Soochow University Suzhou 215025 ChinaInstitute of Pediatric Research Children's Hospital of Soochow University Suzhou 215025 ChinaMolecular Diagnosis and Treatment Center for Infectious Diseases Dermatology Hospital of Southern Medical University Guangzhou Guangdong 510091 ChinaMolecular Diagnosis and Treatment Center for Infectious Diseases Dermatology Hospital of Southern Medical University Guangzhou Guangdong 510091 ChinaMolecular Diagnosis and Treatment Center for Infectious Diseases Dermatology Hospital of Southern Medical University Guangzhou Guangdong 510091 ChinaInstitute for Engineering Medicine Kunming Medical University Kunming 650500 ChinaInstitute for Engineering Medicine Kunming Medical University Kunming 650500 ChinaMolecular Diagnosis and Treatment Center for Infectious Diseases Dermatology Hospital of Southern Medical University Guangzhou Guangdong 510091 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaDepartment of Microbiology School of Public Health Southern Medical University Guangzhou 510515 ChinaMolecular Diagnosis and Treatment Center for Infectious Diseases Dermatology Hospital of Southern Medical University Guangzhou Guangdong 510091 ChinaSchool of Inspection Ningxia Medical University Yinchuan Ningxia 750004 ChinaSchool of Inspection Ningxia Medical University Yinchuan Ningxia 750004 ChinaDepartment of Microbiology School of Public Health Southern Medical University Guangzhou 510515 ChinaDepartment of Microbiology School of Public Health Southern Medical University Guangzhou 510515 ChinaInstitute for Engineering Medicine Kunming Medical University Kunming 650500 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaDepartment of Critical Care Medicine Renmin Hospital of Wuhan University Wuhan 430060 ChinaInstitute of Pediatric Research Children's Hospital of Soochow University Suzhou 215025 ChinaSchool of Inspection Ningxia Medical University Yinchuan Ningxia 750004 ChinaAbstract 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.https://doi.org/10.1002/advs.202412799broad‐spectrum anti‐inflammationolaparibparthanatospH‐responsive capsulessepsis‐induced intestinal injury |
| spellingShingle | 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 Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition Advanced Science broad‐spectrum anti‐inflammation olaparib parthanatos pH‐responsive capsules sepsis‐induced intestinal injury |
| title | Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition |
| title_full | Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition |
| title_fullStr | Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition |
| title_full_unstemmed | Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition |
| title_short | Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition |
| title_sort | intestine decipher engineered capsules protect against sepsis induced intestinal injury via broad spectrum anti inflammation and parthanatos inhibition |
| topic | broad‐spectrum anti‐inflammation olaparib parthanatos pH‐responsive capsules sepsis‐induced intestinal injury |
| url | https://doi.org/10.1002/advs.202412799 |
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