[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-407201-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-407201-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","precision-targeting-of-fdx1-mediated-cuproptosis-by-a-ros-responsive-hydrogel-for-myocardial-ischemia-reperfusion-injury-treatment","Precision targeting of FDX1-mediated cuproptosis by a ROS-responsive hydrogel for myocardial ischemia-reperfusion injury treatment","","Myocardial ischemia-reperfusion injury (MIRI) remains a critical clinical challenge driven by intertwined oxidative stress and cuproptosis-dependent cell death. The study develops a ROS-responsive hydrogel, OD@G4CAsi-FDX1, to deliver antioxidant caffeic acid and FDX1-targeted siRNA with spatiotemporal control. In vitro assays evaluate biocompatibility, ROS scavenging, and mitochondrial protection, while in vivo testing uses a murine MIRI model to assess cardiac function, infarct size, and molecular markers.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/precision-targeting-of-fdx1-mediated-cuproptosis-by-a-ros-responsive-hydrogel-for-myocardial-ischemia-reperfusion-injury-treatment/407201/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/precision-targeting-of-fdx1-mediated-cuproptosis-by-a-ros-responsive-hydrogel-for-myocardial-ischemia-reperfusion-injury-treatment/407201.png","ImageObject",300,407,{"name":42,"@type":43},"Finn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",17,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What therapeutic problem does the study address in myocardial ischemia-reperfusion injury (MIRI)?","Question",{"text":63,"@type":64},"It targets MIRI mechanisms involving oxidative stress and cuproptosis-driven cell death, where current therapies do not adequately address both ROS overproduction and copper dysregulation with precise drug delivery.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does the ROS-responsive hydrogel OD@G4CAsi-FDX1 work?",{"text":68,"@type":64},"It is engineered by dynamic Schiff base crosslinking and co-encapsulates caffeic acid for ROS neutralization and FDX1-targeted siRNA to inhibit FDX1-related cuproptosis processes, enabled by sustained ROS-triggered release.",{"name":70,"@type":61,"acceptedAnswer":71},"What outcomes were observed in vitro and in vivo?",{"text":72,"@type":64},"In vitro, the system reduced ROS, preserved mitochondrial membrane potential, and suppressed pro-inflammatory cytokines. In vivo, it reduced infarct size, suppressed cuproptosis markers, and improved cardiac function.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},407201,1790792343,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Theranostics 2026, Vol. 16, Issue 3 1281  \nIvyspring  \nInternational Publisher  \nTheranostics  \n2026; 16(3): 1281-1294. doi: 10.7150/thno.120455  \nResearch Paper  \nPrecision targeting of FDX1-mediated cuproptosis by a ROS-responsive hydrogel for myocardial  \nischemia-reperfusion injury treatment  \nJiayi Hu, Xiaoyi Bao, Meihua Ting, Yecheng Tao, Ran Li, Guosheng Fu, Fuyu Qiu􀀍, Jing Zhao􀀍, Wenbin Zhang􀀍  \nZhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.  \n􀀍 Corresponding authors: Emails: 3309029@zju.edu.cn (F. Qiu), jingzhao123@zju.edu.cn (J. Zhao), 3313011@zju.edu.cn (W. Zhang) .  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2025.06.27; Accepted: 2025.10.16; Published: 2026.01.01  \nAbstract  \nRationale: Myocardial ischemia-reperfusion injury (MIRI) poses a critical clinical challenge due to intertwined oxidative stress and cuproptosis-driven cell death. Current therapies inadequately address dual-pathology mechanisms (ROS overproduction and copper dysregulation), while conventional drug delivery lacks spatiotemporal precision.  \nMethods: A ROS-responsive hydrogel (OD@G4CAsi-FDX1) was engineered via dynamic Schiff base crosslinking between oxidized dextran (OD) and polyamidoamine dendrimers (PAMAM G4). The hydrogel co-encapsulates antioxidant caffeic acid (CA) and FDX1-targeted siRNA (si-FDX1) . In vitro biocompatibility, ROS scavenging, and mitochondrial protection were assessed in primary cardiomyocytes. In vivo efficacy was evaluated in a murine MIRI model following intramyocardial hydrogel injection. Cardiac function, infarct size, and molecular markers were analyzed.  \nResults: In vitro, it reduced ROS, preserved mitochondrial membrane potential, and suppressed pro-inflammatory cytokines. In vivo, it reduced infarct size, suppressed cuproptosis markers, and improved cardiac function. Mechanistically, si-FDX1 blocked DLAToligomerization, while CA neutralized ROS, synergistically restoring redox homeostasis. This efficacy was enabled by sustained ROS-triggered release.  \nConclusions: OD@G4CAsi-FDX1 hydrogel dual-targets ROS and cuproptosis via a single injectable platform, overcoming limitations of conventional mono-mechanistic therapies. It demonstrates significant cardioprotection and clinical potential for MIRI management.  \nKeywords: myocardial ischemia-reperfusion injury; cuproptosis; oxidative stress; ferredoxin 1; ROS-responsive & scavenging  \nIntroduction  \nMyocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge in acute myocardial infarction (MI) management, significantly worsening patient outcomes. The pathophysiology of MIRI is complex, involving mitochondrial dysfunction, oxidative stress, and inflammatory cascades [1] . Mitochondria, the cellular powerhouses responsible for energy production, are essential for maintaining the functional stability of cardiomyocytes. Mitochondrial dysfunction not only amplifies oxidative damage via excessive reactive oxygen species (ROS) production [2] but also activates multiple cell death pathways, including apoptosis and necrosis [3] . In turn, these pathways can further  \nexacerbate mitochondrial damage, creating a self-reinforcing cycle that ultimately leads to cardiac functional impairment [4] .  \nCuproptosis is a novel form of regulated cell death characterized by copper dependency and associated with mitochondrial metabolism. Copper ions (Cu ions), essential for cellular respiration and energy metabolism, are tightly regulated to maintain normal","cbCaieIfYeTjE78T","https://ap.wps.com/l/cbCaieIfYeTjE78T","pdf",35390736,14,"English","# Abstract\n## Rationale\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What therapeutic problem does the study address in myocardial ischemia-reperfusion injury (MIRI)?\",\"answer\":\"It targets MIRI mechanisms involving oxidative stress and cuproptosis-driven cell death, where current therapies do not adequately address both ROS overproduction and copper dysregulation with precise drug delivery.\"},{\"question\":\"How does the ROS-responsive hydrogel OD@G4CAsi-FDX1 work?\",\"answer\":\"It is engineered by dynamic Schiff base crosslinking and co-encapsulates caffeic acid for ROS neutralization and FDX1-targeted siRNA to inhibit FDX1-related cuproptosis processes, enabled by sustained ROS-triggered release.\"},{\"question\":\"What outcomes were observed in vitro and in vivo?\",\"answer\":\"In vitro, the system reduced ROS, preserved mitochondrial membrane potential, and suppressed pro-inflammatory cytokines. In vivo, it reduced infarct size, suppressed cuproptosis markers, and improved cardiac function.\"}]","Precision targeting of FDX1-mediated cuproptosis by a ROS-responsive hydrogel for myocardial ischemia-reperfusion injury treatment | PDF",1790571691,35]