[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-331735-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-331735-en":130},{"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","interleukin-15-presenting-nanovesicles-with-doxorubicin-loaded-ferritin-cores-for-cancer-immunochemotherapy","Interleukin 15-Presenting Nanovesicles with Doxorubicin-Loaded Ferritin Cores for Cancer Immunochemotherapy","","Interleukin 15 (IL15) is essential for sustaining and expanding natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), but systemic IL15 supplementation can cause inflammation and non-specific activation of cancer cells. This work reports DoxFILN nanovesicles that display IL15/IL15 receptor complexes on their membrane and carry doxorubicin-loaded ferritin cores. DoxFILN increases intratumoral CTL/NK density and activity, promotes immunogenic cell death, and boosts CTL/NK proliferation via tumor microenvironment triggered release and IL15 receptor signaling.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/interleukin-15-presenting-nanovesicles-with-doxorubicin-loaded-ferritin-cores-for-cancer-immunochemotherapy/331735/",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/interleukin-15-presenting-nanovesicles-with-doxorubicin-loaded-ferritin-cores-for-cancer-immunochemotherapy/331735.png","ImageObject",300,407,{"name":42,"@type":43},"Valentina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-02","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is IL15 important for cancer control?","Question",{"text":63,"@type":64},"IL15 supports the survival and proliferation of effector immune cells, including NK cells and CTLs, which contributes to tumor eradication.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What problems limit current IL15 supplementary therapy?",{"text":68,"@type":64},"Systemic inflammation and non-specific immune activation can occur, and IL15 may also bind cancer-cell receptors in ways that promote tumor proliferation and migration.",{"name":70,"@type":61,"acceptedAnswer":71},"How does the DoxFILN nanovesicle enhance immunochemotherapy?",{"text":72,"@type":64},"DoxFILN uses acidic tumor microenvironment triggered release to deliver doxorubicin-loaded ferritin and membrane-bound IL15 receptor complexes, leading to increased CTL/NK activation and immunogenic cell death.","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},331735,1790174652,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nInterleukin 15-Presenting Nanovesicles with Doxorubicin-Loaded Ferritin Cores for Cancer Immunochemotherapy  \nYihui Zhai, Wen Zhang, Jinming Wang, Ying Kong, Rong Rong, Tianqun Lang, Chao Zheng, Yanke Wang, Yang Yu, Helen He Zhu, Ying Cai,* Pengcheng Zhang,* and Yaping Li*  \nInterleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non-specific stimulation of cancer cells. Herein, a nanovesicle termed DoxFILN, comprising a membrane presenting IL15/IL15 receptor 􀀂 complexes (IL15c) and a core of doxorubicin-loaded ferritin (Dox-Fn) are reported. The DoxFILN significantly enhances the densities and activities of intratumoral CTLs and NK cells.  \nMechanistically, DoxFILN undergoes deshelling in the acidic tumor microenvironment, releasing Dox-Fn and membrane-bound IL15c. Dox-Fn selectively target transferrin receptors on cancerous cells, facilitating intracellular Dox release and inducing immunogenic cell death. Concurrently, membrane-bound IL15c recognizes and activates IL15 receptor 􀀃/􀀄cheterodimers, leading to a remarkable increase in the proliferation and activation ofCTLs (16-fold and 28-fold) and NK cells (37-fold and 50-fold). The IL15-displaying nanovesicle introduced here holds promise as a potential platform for immunochemotherapy in the treatment of cancer.  \n1. Introduction  \nInterleukin 15 (IL15) plays a pivotal role in disease control by fostering the survival and proliferation of effector cells from both innate and adaptive immunity.[1] Elevated levels of intratumoral or peritumoral IL15 are positively correlated with a favorable prognosis in hepatocellular carcinoma or colorectal cancer patients. [2] This correlation is grounded in IL15-mediated activation, involving both neoantigen-dependent and independent mechanisms, contributing to effective tumor eradication. [3] Mechanistically, the anti-tumor activity of IL15 relies on its ability to stimulate immune cells expressing IL15 receptor 􀀂/􀀃c heterodimer (IL15R􀀂/􀀃c) . This stimulation occurs through the membranebound IL15/IL15 receptor 􀀄 (IL15R􀀄) complex (IL15c), which is trans-presented by various cells, particularly dendritic cells (DCs) exposed to inflammatory stimuli. [4]  \nY. Zhai, T. Lang, Y. Cai, Y. Li  \nState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica  \nChinese Academy of Sciences  \n501 Haike Road, Shanghai 201203, China  \nE-mail: [s19-caiying@simm.ac.cn](s19-caiying@simm.ac.cn); [ypli@simm.ac.cn](ypli@simm.ac.cn)  \nY. Zhai, T. Lang, Y. Cai, Y. Li  \nUniversity of Chinese Academy of Sciences Beijing 100049, China  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202409194](https://doi.org/10.1002/advs.202409194)[ ](https://doi.org/10.1002/advs.202409194)© 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.1002/advs.202409194  \nW. Zhang, C. Zheng  \nState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica  \nChinese Academy of Sciences Shanghai 201203, China  \nW. Zhang, C. Zheng  \nChina State Institute of Pharmaceutical Industry Shanghai 201203, China  \nJ. Wang, H. H. Zhu  \nState Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research Center  \nDepartment of Urology Ren Ji Hospital  \nSchool of Medicine and School of Biomedical Engineering Shanghai Jiao Tong University  \nShanghai 200127, China  \nY. Kong, R. Rong  \nYantai Institute of Materia Medica Shandong 264000, China  \nAdv.","cbCaitP73pZNcAZv","https://ap.wps.com/l/cbCaitP73pZNcAZv","pdf",5471919,14,"English","# Introduction\n## IL15 as a key cytokine in tumor control\n## Challenges in IL15 supplementary therapy\n## Strategies to improve efficacy and safety\n## Tumor microenvironment barriers and treatment synergy","[{\"question\":\"Why is IL15 important for cancer control?\",\"answer\":\"IL15 supports the survival and proliferation of effector immune cells, including NK cells and CTLs, which contributes to tumor eradication.\"},{\"question\":\"What problems limit current IL15 supplementary therapy?\",\"answer\":\"Systemic inflammation and non-specific immune activation can occur, and IL15 may also bind cancer-cell receptors in ways that promote tumor proliferation and migration.\"},{\"question\":\"How does the DoxFILN nanovesicle enhance immunochemotherapy?\",\"answer\":\"DoxFILN uses acidic tumor microenvironment triggered release to deliver doxorubicin-loaded ferritin and membrane-bound IL15 receptor complexes, leading to increased CTL/NK activation and immunogenic cell death.\"}]","Interleukin 15-Presenting Nanovesicles with Doxorubicin-Loaded Ferritin Cores for Cancer Immunochemotherapy | PDF",1789994933,35]