Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury

Drug-induced liver injury (DILI) is a major clinical concern associated with drug toxicity, primarily characterized by hepatocyte damage driven by oxidative stress and inflammation. Excessive accumulation of reactive oxygen species (ROS) and pro-inflammatory cytokines exacerbates liver injury, neces...

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Main Authors: Wenxing Gu, Ruxue Bai, Jiaxin Wang, Jun Wang, Chongzhou Fang, Yuanchao Shi, Peixing Wang, Qiaoqiao Wang, Wei Bing, Tian Xie, Jing Mu
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425007392
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author Wenxing Gu
Ruxue Bai
Jiaxin Wang
Jun Wang
Chongzhou Fang
Yuanchao Shi
Peixing Wang
Qiaoqiao Wang
Wei Bing
Tian Xie
Jing Mu
author_facet Wenxing Gu
Ruxue Bai
Jiaxin Wang
Jun Wang
Chongzhou Fang
Yuanchao Shi
Peixing Wang
Qiaoqiao Wang
Wei Bing
Tian Xie
Jing Mu
author_sort Wenxing Gu
collection DOAJ
description Drug-induced liver injury (DILI) is a major clinical concern associated with drug toxicity, primarily characterized by hepatocyte damage driven by oxidative stress and inflammation. Excessive accumulation of reactive oxygen species (ROS) and pro-inflammatory cytokines exacerbates liver injury, necessitating effective therapeutic interventions. While natural antioxidant enzymes exhibit high catalytic activity and specificity in ROS scavenging, their clinical use is limited by poor stability in circulation and limited cellular uptake. To address these challenges, we developed antioxidant polymersomal nanoreactors (CS@PS) for the targeted co-delivery of catalase (CAT) and superoxide dismutase (SOD). CS@PS functions as a cascade system, efficiently neutralizing ROS and mitigating inflammation in hepatocytes. Notably, systemic administration of CS@PS exhibits targeted delivery to hepatocytes, ensuring enzyme stability and bioavailability. In a model of acetaminophen-induced liver injury, CS@PS significantly reduced hepatic ROS levels and alleviated liver damage, underscoring its therapeutic potential. This study highlights the promise of CS@PS as an innovative antioxidant nanoreactor for DILI treatment offer a promising strategy for managing other ROS-mediated diseases.
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publishDate 2025-10-01
publisher Elsevier
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spelling doaj-art-e422348d86204dc382db6872cc90df562025-08-20T02:57:22ZengElsevierMaterials Today Bio2590-00642025-10-013410216910.1016/j.mtbio.2025.102169Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injuryWenxing Gu0Ruxue Bai1Jiaxin Wang2Jun Wang3Chongzhou Fang4Yuanchao Shi5Peixing Wang6Qiaoqiao Wang7Wei Bing8Tian Xie9Jing Mu10Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, China; School of Pharmacy, Zhejiang Provincial Key Laboratory of Anti-Cancer Chinese Medicines and Natural Medicines, Hangzhou Normal University, Hangzhou, 311121, ChinaInstitute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, China; School of Chemistry and Life Science, Changchun University of Technology, Changchun, 130012, ChinaInstitute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, ChinaInstitute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, ChinaInstitute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, ChinaInstitute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, ChinaSchool of Pharmacy, Zhejiang Provincial Key Laboratory of Anti-Cancer Chinese Medicines and Natural Medicines, Hangzhou Normal University, Hangzhou, 311121, ChinaSchool of Pharmacy, Zhejiang Provincial Key Laboratory of Anti-Cancer Chinese Medicines and Natural Medicines, Hangzhou Normal University, Hangzhou, 311121, ChinaSchool of Chemistry and Life Science, Changchun University of Technology, Changchun, 130012, China; Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, 130022, China; Corresponding author. School of Chemistry and Life Science, Changchun University of Technology, Changchun, 130012, ChinaSchool of Pharmacy, Zhejiang Provincial Key Laboratory of Anti-Cancer Chinese Medicines and Natural Medicines, Hangzhou Normal University, Hangzhou, 311121, China; Corresponding author.Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Corresponding author.Drug-induced liver injury (DILI) is a major clinical concern associated with drug toxicity, primarily characterized by hepatocyte damage driven by oxidative stress and inflammation. Excessive accumulation of reactive oxygen species (ROS) and pro-inflammatory cytokines exacerbates liver injury, necessitating effective therapeutic interventions. While natural antioxidant enzymes exhibit high catalytic activity and specificity in ROS scavenging, their clinical use is limited by poor stability in circulation and limited cellular uptake. To address these challenges, we developed antioxidant polymersomal nanoreactors (CS@PS) for the targeted co-delivery of catalase (CAT) and superoxide dismutase (SOD). CS@PS functions as a cascade system, efficiently neutralizing ROS and mitigating inflammation in hepatocytes. Notably, systemic administration of CS@PS exhibits targeted delivery to hepatocytes, ensuring enzyme stability and bioavailability. In a model of acetaminophen-induced liver injury, CS@PS significantly reduced hepatic ROS levels and alleviated liver damage, underscoring its therapeutic potential. This study highlights the promise of CS@PS as an innovative antioxidant nanoreactor for DILI treatment offer a promising strategy for managing other ROS-mediated diseases.http://www.sciencedirect.com/science/article/pii/S2590006425007392Hepatocyte targetingPolymersomeNanoreactorDrug-induced liver injuryReactive oxygen species
spellingShingle Wenxing Gu
Ruxue Bai
Jiaxin Wang
Jun Wang
Chongzhou Fang
Yuanchao Shi
Peixing Wang
Qiaoqiao Wang
Wei Bing
Tian Xie
Jing Mu
Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury
Materials Today Bio
Hepatocyte targeting
Polymersome
Nanoreactor
Drug-induced liver injury
Reactive oxygen species
title Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury
title_full Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury
title_fullStr Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury
title_full_unstemmed Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury
title_short Biomimetic polymersomal nanoreactors for hepatocyte-directed detoxification in drug-induced liver injury
title_sort biomimetic polymersomal nanoreactors for hepatocyte directed detoxification in drug induced liver injury
topic Hepatocyte targeting
Polymersome
Nanoreactor
Drug-induced liver injury
Reactive oxygen species
url http://www.sciencedirect.com/science/article/pii/S2590006425007392
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