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This study isolates Huangqi derived exosome-like nanoparticles (HELNs) from fresh Astragalus membranaceus and evaluates anti-tumor efficacy in vitro and in vivo. Mechanistically, HELNs reverse M2 macrophage polarization, promote M1-like phenotypes, enhance anti-tumor gut probiotics, and induce ferroptosis by downregulating GPX4. A siGPX4 loading strategy strengthens ferroptosis while preserving safety.",{"@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/therapeutic-translation-of-traditional-chinese-medicine-huangqi-derived-exosome-like-nanoparticles-targeting-prostate-cancer-through-ferroptosis-activation-immune-reprogramming-and-microbiome-modulation/349212/",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/therapeutic-translation-of-traditional-chinese-medicine-huangqi-derived-exosome-like-nanoparticles-targeting-prostate-cancer-through-ferroptosis-activation-immune-reprogramming-and-microbiome-modulation/349212.png","ImageObject",300,407,{"name":42,"@type":43},"Adam","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are HELNs and how are they prepared in this study?","Question",{"text":63,"@type":64},"The study extracts Huangqi derived exosome-like nanoparticles (HELNs) from fresh Huangqi (Astragalus membranaceus).","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do HELNs exert anti-tumor effects in prostate cancer?",{"text":68,"@type":64},"HELNs show cytotoxic effects in vitro and in vivo, reverse M2 macrophage polarization toward an M1-like state, increase anti-tumor probiotics in the gut, and induce ferroptosis by downregulating GPX4 protein in prostate cancer cells.",{"name":70,"@type":61,"acceptedAnswer":71},"Why create siGPX4@HELNs, and what is the outcome?",{"text":72,"@type":64},"siGPX4 is loaded into HELNs to form siGPX4@HELNs, which induces more pronounced ferroptosis in prostate cancer cells and achieves improved therapeutic outcomes while maintaining safety.","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},349212,1790856053,{"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},1374404737137,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","An etal. Journal of Nanobiotechnology (2026) 24:447 Journal of Nanobiotechnology  \n[https://doi.org/10.1186/s12951-026-04160-4](https://doi.org/10.1186/s12951-026-04160-4)  \nRESEARCH Open Access  \nTherapeutic translation of traditional Chinese  medicine Huangqi derived exosome like nanoparticles: targeting prostate cancer through ferroptosis activation, immune reprogramming, and microbiome modulation  \nYe An1†, Jin-Zhou Xu1†, Gui-Chen Ye1†, Jian-Xuan Sun 1, Jia-Cheng Xiang1, Chen Gong2, Si-Han Zhang1, Lin-Tao Miao 1, Si-Yang Ma1, Ming-Xia Ding3*, Shao-Gang Wang1* and Qi-Dong Xia1*  \nAbstract  \nPlant derived exosome-like nanoparticles (PELNs) are emerging as a powerful tool for treating cancers. Among them, PELNs derived from traditional Chinese medicines have shown great potential in treating various cancers. However, many Chinese medicines remain to be explored, and currently, there are no reports on the use of PELNs for treating prostate cancer. In this study, we extracted Huangqi derived exosome-like nanoparticles (HELNs) from fresh Huangqi (Astragalus membranaceus) and systematically explored the effects and mechanisms of HELNs in treating prostate cancer through an integrated approach of single-cell sequencing, 16 S rDNA sequencing, and bulk-RNA sequencing. We found that HELNs demonstrated robust cytotoxic effects against prostate cancer both in vitro and in vivo. HELNs reverse the polarization of M2 macrophages, promote their M1-like polarization, and increase the abundance of anti-tumor probiotics in the gut to exert anti-tumor effects. In terms of direct effects, HELNs downregulate the expression level of GPX4 protein in prostate cancer cells, thereby inducing ferroptosis. Finally, we loaded siGPX4 into HELNs to construct a new nanoparticle siGPX4@HELNs. siGPX4@HELNs induce more pronounced ferroptosis in prostate cancer cells, achieving better therapeutic outcomes while maintaining safety. Keywords Plant derived exosome-like nanoparticles, Macrophages, Ferroptosis, Prostate cancer, Drug delivery  \n†Ye An, Jin-Zhou Xu and Gui-Chen Ye contributed equally to this work.  \n*Correspondence:  \nMing-Xia Ding [dingmingxia@kmmu.edu.cn](dingmingxia@kmmu.edu.cn)[ ](dingmingxia@kmmu.edu.cn)Shao-Gang Wang [sgwangtjm@163.com](sgwangtjm@163.com)  \nQi-Dong Xia [qidongxia_md@163.com](qidongxia_md@163.com)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026, modified publication 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://cre](http://cre)[ativecommons.org/licenses/by-nc-nd/4.0/](ativecommons.org/licenses/by-nc-nd/4.0/.)[.](ativecommons.org/licenses/by-nc-nd/4.0/.)  \nAn et al. Journal of Nanobiotechnology (2026) 24:447 Page 2 of 23  \nGraphical abstract  \nIntroduction  \nProstate cancer (PCa) is one of the most common malignant tumors in the male urinary and reproductive system worldwide, ranking second in incidence and fifth in mortality among all male cancers. Global estimates for 2020 indicated approximately 1.4 million new cases and 370,000 deaths from prostate cancer [1","cbCaib6eg1iZAGjM","https://ap.wps.com/l/cbCaib6eg1iZAGjM","pdf",16246853,23,"English","# Abstract\n# Introduction","[{\"question\":\"What are HELNs and how are they prepared in this study?\",\"answer\":\"The study extracts Huangqi derived exosome-like nanoparticles (HELNs) from fresh Huangqi (Astragalus membranaceus).\"},{\"question\":\"How do HELNs exert anti-tumor effects in prostate cancer?\",\"answer\":\"HELNs show cytotoxic effects in vitro and in vivo, reverse M2 macrophage polarization toward an M1-like state, increase anti-tumor probiotics in the gut, and induce ferroptosis by downregulating GPX4 protein in prostate cancer cells.\"},{\"question\":\"Why create siGPX4@HELNs, and what is the outcome?\",\"answer\":\"siGPX4 is loaded into HELNs to form siGPX4@HELNs, which induces more pronounced ferroptosis in prostate cancer cells and achieves improved therapeutic outcomes while maintaining safety.\"}]","Therapeutic translation of traditional Chinese medicine Huangqi derived exosome like nanoparticles - targeting prostate cancer through ferroptosis activation, immune reprogramming, and microbiome modulation | PDF",1790082234,58]