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Pyroptosis involves cell swelling, membrane rupture, and release of pro-inflammatory cytokines, which can potentiate immune responses. Here, hollow spiky manganese oxide (HSpiM) nanocarriers enhance RT-induced pyroptosis and trigger anti-tumor immunity by promoting lysosomal rupture, increasing ROS, activating NLRP3 inflammasome, inhibiting autophagy, and enabling membrane repair disruption via BA@HSpiM. RT-induced pyroptosis suppresses metastasis and generates durable immune memory.",{"@graph":69,"@context":122},[70,84,105],{"@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/hollow-spiky-mnox-nanocarriers-amplify-radiotherapy-induced-pyroptosis-for-eliciting-antitumor-immunity/457697/",{"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/hollow-spiky-mnox-nanocarriers-amplify-radiotherapy-induced-pyroptosis-for-eliciting-antitumor-immunity/457697.png","ImageObject",300,407,{"name":92,"@type":93},"Mafia Boss","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-04","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why does radiotherapy induce limited anti-tumor immunity when it mainly triggers apoptosis?","Question",{"text":112,"@type":113},"Apoptosis keeps the tumor cell membrane intact, which conceals the release of immunogenic DAMPs and reduces immune-cell activation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role do hollow spiky MnOx (HSpiM) nanocarriers play in enhancing radiotherapy-induced pyroptosis?",{"text":117,"@type":113},"Their spiked structure promotes intracellular lysosomal rupture, and after RT they generate elevated ROS to synergistically activate the NLRP3 inflammasome, amplifying pyroptosis.",{"name":119,"@type":110,"acceptedAnswer":120},"How does BA@HSpiM increase tumor pyroptosis beyond HSpiM alone?",{"text":121,"@type":113},"By encapsulating an ESCRT inhibitor, the Ca2+ chelator BAPTA-AM, BA@HSpiM promotes tumor pyroptosis through disrupting the repair of damaged cell membranes, leading to stronger immunogenic cell death.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},457697,1790818695,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31},962090760730,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Zhang et al. Journal of Nanobiotechnology (2026) 24:19  \n[https://doi.org/10.1186/s12951-025-03789-x](https://doi.org/10.1186/s12951-025-03789-x)  \nJournal of Nanobiotechnology  \nRESEARCH Open Access  \nHollow spiky MnOx nanocarriers amplify  radiotherapy-induced pyroptosis for eliciting antitumor immunity  \nYifan Zhang 1, Yuqian Liu 1, Bin Hu 1, Xianglong Sun 1, Jiadong Wang 1, Zheng Deng 1, Xirui Wu 1, Cai Zhang 1, Yueyue Jing 1, Junjun Zhang2*, Rongrui Liang 1* and Guangbao Yang 1*  \nAbstract  \nRadiotherapy (RT) is a primary modality in clinical cancer treatment. However, its ability to induce tumor cell apoptosis offers limited activation of anti-tumor immunity. Pyroptosis, characterized by cell swelling, membrane rupture, and the release of pro-inflammatory cytokines, has been demonstrated to potentiate immune responses against cancer cells. Herein, we develop hollow spiky manganese oxide (HSpiM) nanocarriers to enhance RTinduced tumor pyroptosis and elicit anti-tumor immune responses. The spiked structure of HSpiM nanocarriers promotes intracellular lysosomal rupture, while simultaneously producing elevated amounts of reactive oxygen species (ROS) after RT, to synergistically activate the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. Notably, lysosomal rupture-induced autophagy inhibition amplifies NLRP3-mediated pyroptosis by blocking lysosome-mediated degradation pathways. Moreover, we encapsulate an ESCRT inhibitor, the Ca2+ chelator BAPTA-AM, into HSpiM nanocarriers (designated as BA@HSpiM) to promote tumor pyroptosis by disrupting the repair of damaged cell membranes. RT-induced pyroptosis elicits potent anti-tumor immunity, effectively suppressing tumor metastasis and generating durable immune memory to reject tumor rechallenge. Overall, inducing tumor pyroptosis presents a promising strategy to enhance the efficacy of RT, as it improves the outcomes of local treatment and activates systemic anti-tumor immune responses.  \nKeywords Radiotherapy, Pyroptosis, Manganese oxide, Anti-tumor immunity  \n*Correspondence:  \nJunjun Zhang [sudazhangjunjun@126.com](sudazhangjunjun@126.com)[ ](sudazhangjunjun@126.com)Rongrui Liang[lengbeng@suda.edu.cn](lengbeng@suda.edu.cn)[ ](lengbeng@suda.edu.cn)Guangbao Yang [yangguangbao@suda.edu.cn](yangguangbao@suda.edu.cn)  \nFull list of author information is available at the end of the article  \nIntroduction  \nIn recent decades, an increasing number of programmed cell death types have been reported, including autophagy, pyroptosis, and ferroptosis [1–6]. Despite significant differences in phenotype and regulatory signaling pathways among different types of cell death, there may be associations between these pathways, enabling the conversion of one type of cell death into another [7]. The distinctions between different modes of cell death provide promising strategies for enhancing the efficacy of cancer therapy. Radiotherapy (RT) is a vital therapeutic approach in cancer treatment, primarily inducing apoptosis in cancer cells by directly damaging DNA and generating cytotoxic  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 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 ","cbCairgg2u1vKUSe","https://ap.wps.com/l/cbCairgg2u1vKUSe","pdf",16833505,"English","# Abstract\n# Introduction\n## Programmed cell death and radiotherapy\n## Immunogenicity: apoptosis versus pyroptosis\n## Classical pyroptosis pathway and NLRP3 activation","[{\"question\":\"Why does radiotherapy induce limited anti-tumor immunity when it mainly triggers apoptosis?\",\"answer\":\"Apoptosis keeps the tumor cell membrane intact, which conceals the release of immunogenic DAMPs and reduces immune-cell activation.\"},{\"question\":\"What role do hollow spiky MnOx (HSpiM) nanocarriers play in enhancing radiotherapy-induced pyroptosis?\",\"answer\":\"Their spiked structure promotes intracellular lysosomal rupture, and after RT they generate elevated ROS to synergistically activate the NLRP3 inflammasome, amplifying pyroptosis.\"},{\"question\":\"How does BA@HSpiM increase tumor pyroptosis beyond HSpiM alone?\",\"answer\":\"By encapsulating an ESCRT inhibitor, the Ca2+ chelator BAPTA-AM, BA@HSpiM promotes tumor pyroptosis through disrupting the repair of damaged cell membranes, leading to stronger immunogenic cell death.\"}]","Hollow spiky MnOx nanocarriers amplify radiotherapy-induced pyroptosis for eliciting antitumor immunity | PDF",1790750185]