[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-407290-105":59,"doc-detail-407290-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","cuproptosis-triggering-nanomedicine-boosts-antitumor-immunotherapy","Cuproptosis-triggering nanomedicine boosts antitumor immunotherapy","","Cuproptosis is a copper-dependent programmed cell death driven by mitochondrial copper accumulation and proteotoxic stress, offering a strategy to strengthen antitumor immunity. Yet conventional cuproptosis inducers are limited by short circulation half-lives, dose-dependent systemic toxicity, and insufficient tumor targeting. Advanced nanoplatforms improve targeted cuproptosis induction and immune activation. This review details immune-activating mechanisms and highlights nanomaterial advances and translational challenges for clinical immunotherapy.",{"@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/cuproptosis-triggering-nanomedicine-boosts-antitumor-immunotherapy/407290/",{"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/cuproptosis-triggering-nanomedicine-boosts-antitumor-immunotherapy/407290.png","ImageObject",300,407,{"name":92,"@type":93},"Liam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",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 is cuproptosis and how does it drive antitumor immunity?","Question",{"text":113,"@type":114},"Cuproptosis is a copper-dependent programmed cell death caused by mitochondrial copper accumulation, which triggers proteotoxic stress and cell death. Its immune activation effects can enhance antitumor immunity through multiple pathways in the tumor setting.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why do conventional cuproptosis inducers face translational limitations?",{"text":118,"@type":114},"They have short blood circulation half-lives, can cause dose-dependent systemic toxicity, and often fail to achieve adequate tumor targeting. These issues reduce therapeutic effectiveness and clinical feasibility.",{"name":120,"@type":111,"acceptedAnswer":121},"How do nanomedicine platforms address these challenges?",{"text":122,"@type":114},"They enable precise, tumor-targeted induction of cuproptosis while improving immune activation. The review emphasizes cutting-edge nanomaterial strategies that can be used alone or combined with other antitumor modalities.","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},407290,1790815790,{"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":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Theranostics 2026, Vol. 16, Issue 5 2405  \nIvyspring  \nInternational Publisher  \nTheranostics  \n2026; 16(5): 2405-2446. doi: 10.7150/thno.123080  \nReview  \nCuproptosis-triggering nanomedicine boosts antitumor immunotherapy  \nMaoshan Wang, Chunyu Shi, Zhenbo Shu􀀍, Zhongmin Li􀀍  \nDepartment of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China.  \n􀀍 Corresponding authors: Zhenbo Shu ([shuzb@jlu.edu.cn](shuzb@jlu.edu.cn)), Zhongmin Li ([lizhongmin1211@jlu.edu.cn](lizhongmin1211@jlu.edu.cn)) .  \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: 2025.08.04; Accepted: 2025.11.18; Published: 2026.01.01  \nAbstract  \nCuproptosis, a copper-dependent programmed cell death triggered by mitochondrial copper accumulation and subsequent proteotoxic stress, has emerged as a promising strategy to enhance antitumor immunity. However, conventional cuproptosis inducers face critical limitations such as short blood circulation half-lives, dose-dependent systemic toxicity, and inadequate tumor targeting. To address these challenges, advanced nanoplatforms have been developed to enable precise tumor-targeted cuproptosis induction and immune activation. This review summarizes the immune-activating mechanisms of cuproptosis, including its roles in promoting immune cell maturation and infiltration, remodeling the immunosuppressive tumor microenvironment, modulating immune checkpoint molecule expression, and activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. We highlight cutting-edge advancements in nanomaterial-based strategies for triggering cuproptosis, which enhance antitumor immunity whether used as a single treatment or in combination with other antitumor modalities. The current challenges in translating cuproptosis-based therapies into clinical applications are proposed to promote the development of cuproptosis-triggering nanomedicines as next-generation immunotherapy strategy.  \nKeywords: cuproptosis, nanomedicine, antitumor immunotherapy, combination therapy  \n1. Introduction  \nCopper, an essential trace element, plays a critical role in various physiological processes. It functions as both a cofactor for enzymes involved in energy metabolism and neurotransmitter synthesis and as a metal allosteric modulator that regulates intracellular signal transduction [1] . The cellular uptake of copper ions is primarily mediated by the high-affinity copper transporter 1 (CTR1), which is encoded by the SLC31A1 gene [2] . This protoncoupled transport mechanism ensures selective and efficient copper acquisition, with optimal activity observed under slightly acidic conditions. Following internalization, copper is rapidly bound by specific chaperones to mitigate potential oxidative damage. Concurrently, intricate regulatory pathways are activated to maintain copper homeostasis, achieving a critical balance between preventing toxicity and ensuring adequate availability for essential cellular functions. When intracellular copper levels exceed the  \nthreshold maintained by cellular homeostatic mechanisms, it becomes cytotoxic and may lead to cell death [3] . Although copper overload was known to induce cell death, the underlying mechanism remains unclear. In 2022, Tsvetkov et al. identified\"cuproptosis\", a novel form of mitochondrial respiration-dependent cell death driven by copper overload [4] . This process involves excessive intracellular copper ions binding to lipoylated proteins in the mitochondrial tricarboxylic acid (TCA) cycle, leading to protein aggregation and depletion of iron-sulfur (Fe-S) clusters, which in turn induces proteotoxic stress and ultimately leads to cell death [5]","cbCaioE74drq279G","https://ap.wps.com/l/cbCaioE74drq279G","pdf",11641867,42,"English","# Introduction\n## Copper homeostasis and cuproptosis mechanisms\n## Tumor dependence on copper and biomarker value\n## Nanomedicine strategies for inducing cuproptosis","[{\"question\":\"What is cuproptosis and how does it drive antitumor immunity?\",\"answer\":\"Cuproptosis is a copper-dependent programmed cell death caused by mitochondrial copper accumulation, which triggers proteotoxic stress and cell death. Its immune activation effects can enhance antitumor immunity through multiple pathways in the tumor setting.\"},{\"question\":\"Why do conventional cuproptosis inducers face translational limitations?\",\"answer\":\"They have short blood circulation half-lives, can cause dose-dependent systemic toxicity, and often fail to achieve adequate tumor targeting. These issues reduce therapeutic effectiveness and clinical feasibility.\"},{\"question\":\"How do nanomedicine platforms address these challenges?\",\"answer\":\"They enable precise, tumor-targeted induction of cuproptosis while improving immune activation. The review emphasizes cutting-edge nanomaterial strategies that can be used alone or combined with other antitumor modalities.\"}]","Cuproptosis-triggering nanomedicine boosts antitumor immunotherapy | PDF",1790572725,106]