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Excess reactive oxygen species (ROS) trigger inflammatory signaling, increase transcription of proinflammatory mediators, and can culminate in tissue damage and fibrosis. The study develops a bilirubin-based ROS-sensitive adaptive nanoscavenger (GP@BR) using different bilirubin conjugates to provide on-demand antioxidative activity, ROS-triggered effects, cytokine absorption, and enhanced transport across the mucosal layer, with in vivo evidence of improved ALI symptoms and reduced pulmonary fibrosis.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/adaptive-bilirubin-nanoscavenger-alleviates-pulmonary-oxidative-stress-and-inflammation-for-acute-lung-injury-therapy/434355/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/adaptive-bilirubin-nanoscavenger-alleviates-pulmonary-oxidative-stress-and-inflammation-for-acute-lung-injury-therapy/434355.png","ImageObject",300,407,{"name":92,"@type":93},"Aria Callaghan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does oxidative stress play in acute lung injury progression?","Question",{"text":113,"@type":114},"Oxidative stress in lung tissue activates inflammatory signaling pathways, increasing proinflammatory factor transcription and worsening tissue injury, which can contribute to necrosis and fibrosis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is GP@BR and how was it constructed?",{"text":118,"@type":114},"GP@BR is a bilirubin-based ROS-sensitive adaptive nanoscavenger formed by co-assembling bilirubin-conjugated glycol chitosan (GC-BR) and bilirubin-conjugated polyethylene glycol (PEG-BR).",{"name":120,"@type":111,"acceptedAnswer":121},"How do the bilirubin conjugations affect nanoscavenger function and delivery?",{"text":122,"@type":114},"Different conjugations provide varying ROS sensitivity, enabling antioxidative activity specifically in oxidative environments. The system also supports transport across the mucosal layer and can absorb excess inflammatory cytokines.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},434355,1790766485,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Journal of Advanced Research 79 (2026) 863–878  \nContents lists available at ScienceDirect  \nJournal of Advanced Research  \njournal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare)  \nOriginal Manuscript  \nAdaptive bilirubin nanoscavenger alleviates pulmonary oxidative stress and inflammation for acute lung injury therapy  \nLongfa Kou a,b,c,⁎, 1, Yitianhe Xu a,b, 1, Shize Li a,b, 1, Zhinan He a,b,c, Di Huang a,c, Zhanzheng Ye a,b,c,  \nYixuan Zhu a,b,c, Yunzhi Wang a,b,c, Xinyu Di a,b,c, Yuqi Yan a,b,c, Yinhao Lin a,b,c, Wanling Zhu d, Xianbao Shi d, Hailin Zhang a,b,e,⁎, Ruijie Chen a,b,⁎  \na Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China  \nb Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, China c School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China  \nd Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China  \ne Department of Children’s Respiration Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China  \nh i g h l i g h t s  \n• Bilirubin is a potent ROS scavenger and a potential drug for acute lung injury therapy.  \n• Different conjugates endow the bilirubin derivatives with varying sensitivity against ROS.  \n• bilirubin-based ROS-sensitive adaptive nanoscavenger was developed in this study.  \n• The nanoscavenger could facilitate efficient transport across the mucosal layer.  \ng r a p h i c a l a b s t r a c t  \na r t i c l e i n f o  \nArticle history:  \nReceived 1 December 2024 Revised 12 March 2025  \nAccepted 15 March 2025  \nAvailable online 17 March 2025  \nKeywords:  \nBilirubin nanoparticles Acute lung injury Oxidative stress Mucus  \nInflammatory cytokines  \na b s t r a c t  \nIntroduction: Acute lung injury (ALI) is a life-threatening condition characterized by rapidly progressing respiratory distress and hypoxemia. Oxidative stress-induced inflammation in lung tissue plays a crucial role in the progression of ALI. Excessive generation of reactive oxygen species (ROS) in the pulmonary microenvironment activates inflammatory signaling pathways, enhancing the transcription of proinflammatory factors and ultimately leading to tissue necrosis.  \nObjectives: Bilirubin (BR), an exceptional endogenous antioxidant, possesses the ability to counteract elevated levels of reactive oxygen species (ROS) through direct reactions or by inducing antioxidant systems such as Nrf2/HO-1 signaling. However, its limited solubility poses a hindrance to further applications. Hence, it is imperative to develop a suitable bilirubin-based system for biological utilization.  \nMethods: In this study, we developed a bilirubin-based ROS-sensitive adaptive nanoscavenger (GP@BR) by co-assembling bilirubin-conjugated glycol chitosan (GC-BR) and bilirubin-conjugated polyethylene glycol (PEG-BR), aiming to alleviate oxidative stress for ALI treatment.  \nResults: The different conjugations endowed the bilirubin derivatives with varying sensitivity towards  \n⁎ Corresponding authors at: Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China.  \nE-mail addresses: [klfpharm@163.com](klfpharm@163.com) (L. Kou), [zhlwz97@hotmail.com](zhlwz97@hotmail.com) (H.  \nZhang), [crjpharm@163.com](crjpharm@163.com) (R. Chen).  \n1 The authors contributed equally to this work.  \n[https://doi.org/10.1016/j.jare.2025.03.027](https://doi.org/10.1016/j.jare.2025.03.027)  \n2090-1232/© 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University.  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://cr","cbCaioXlB1ljZkoN","https://ap.wps.com/l/cbCaioXlB1ljZkoN","pdf",4026922,"English","# Introduction\n## Objectives\n## Methods\n## Results\n## Conclusion","[{\"question\":\"What role does oxidative stress play in acute lung injury progression?\",\"answer\":\"Oxidative stress in lung tissue activates inflammatory signaling pathways, increasing proinflammatory factor transcription and worsening tissue injury, which can contribute to necrosis and fibrosis.\"},{\"question\":\"What is GP@BR and how was it constructed?\",\"answer\":\"GP@BR is a bilirubin-based ROS-sensitive adaptive nanoscavenger formed by co-assembling bilirubin-conjugated glycol chitosan (GC-BR) and bilirubin-conjugated polyethylene glycol (PEG-BR).\"},{\"question\":\"How do the bilirubin conjugations affect nanoscavenger function and delivery?\",\"answer\":\"Different conjugations provide varying ROS sensitivity, enabling antioxidative activity specifically in oxidative environments. The system also supports transport across the mucosal layer and can absorb excess inflammatory cytokines.\"}]","Adaptive bilirubin nanoscavenger alleviates pulmonary oxidative stress and inflammation for acute lung injury therapy | PDF",1790668746]