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This study designs a CPApoptosis (cuproptosis, pyroptosis, apoptosis) nano-actuator using elesclomol-loaded bacterial outer membrane vesicles. Cu2+ and euxclomol release in a pH-dependent manner, driving non-canonical pyroptosis, cuproptosis, and TA/ROS-mediated oxidative apoptosis with GSH degradation, generating immunogenic factor release and enhanced antitumor immunity amplified by anti–PD-L1.",{"@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/cpapoptosis-nano-actuator-switches-immune-off-solid-tumors-to-immune-on-for-fueling-t-cell-based-immunotherapy/375979/",{"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/cpapoptosis-nano-actuator-switches-immune-off-solid-tumors-to-immune-on-for-fueling-t-cell-based-immunotherapy/375979.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",17,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main goal of the CPApoptosis nano-actuator strategy?","Question",{"text":113,"@type":114},"To convert immunologically cold (“immune-off”) solid tumors into an “immune-on” state by inducing multiple immunogenic cell death modalities and strengthening antitumor immune activation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were the therapeutic components prepared in this study?",{"text":118,"@type":114},"Elesclomol was encapsulated in bacterial outer membrane vesicles (OMVs), and the OMVs were surface-modified using Cu2+ and tannic acid via metal-phenolic self-assembly.",{"name":120,"@type":111,"acceptedAnswer":121},"What mechanisms lead to tumor cell death and immune activation?",{"text":122,"@type":114},"The system releases Cu2+ and elesclomol in a pH-dependent manner, activating non-canonical pyroptosis, inducing cuproptosis via mitochondrial delivery, and promoting TA-mediated ROS production and oxidative apoptosis with GSH degradation; lysed tumor cells then release immunogenic factors that stimulate dendritic maturation and recruit cytotoxic T cells, further enhanced by αPD-L1 therapy.","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},375979,1790245268,{"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":26},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Ivyspring  \nInternational Publisher  \nTheranostics  \n2025; 15(9): 3797-3820. doi: 10.7150/thno.105867  \nResearch Paper  \nA “CPApoptosis” nano-actuator switches immune-off solid tumors to immune-on for fueling T-cell-based immunotherapy  \nYing Luo1,2*, Yi Wang1*, Bo Liu1, Yun Liu1, Wenli Zhang1, Sijin Chen1, Xiyue Rong1, Lian Xu1, Qianying Du1, Jia Liu1, Jie Xu1, Haitao Ran2, Zhigang Wang2, Dajing Guo1􀀍  \n1. Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.  \n2. Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.  \n*Equal contribution.  \n􀀍 Corresponding author: [guodaj@hospital.cqmu.edu.cn](guodaj@hospital.cqmu.edu.cn) (Dajing Guo) .  \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: 2024.10.26; Accepted: 2025.02.19; Published: 2025.03.03  \nAbstract  \nBackground: Most anticancer agents induce tumor apoptosis, but they often lack immunogenicity and display limited success when combined with mainstream immunotherapies, thus killing cancer cells through multiple cell death modalities as well as switching immune-off tumors to immune-on is a strategy with great promise. To this end, we developed a CPApoptosis (cuproptosis, pyroptosis, apoptosis) nano-actuator for immunologically cold solid tumors.  \nMethods: In this study, elesclomol (ES), a mitochondrial targeting copper transporter, was encapsulated within bacterial outer membrane vesicles (OMVs). These OMVs were then surface-modified via metal-phenolic self-assembly using Cu2+ and tannic acid (TA).  \nResults: The Cu2+ and ES were released from the OMVs in a pH-dependent manner. OMV activated thenon-canonical pyroptotic pathway, leading to cell membrane rupture. Cu2+ on the one hand was transported to the mitochondria for cuproptosis facilitated by ES, on the other hand, Cu2+ was reduced into Cu+ by TA, which catalyzed ROS production to induce oxidative apoptosis. Simultaneously, TA degraded glutathione (GSH), sensitizing cells to cuproptosis. The multifactorial cell death mechanisms led to the release of immunogenic factors from lysed tumor cells, stimulating dendritic cell maturation and recruiting cytotoxic T cells. This immune response was further amplified by αPD-L1 antibody treatment.  \nConclusion: The CPApoptosis nano-actuator represents a promising approach to enhance current cancer therapies, inducing both tumor cell death and a robust immune response, with the potential for long-lasting protective effects.  \nKeywords: cuproptosis, pyroptosis, apoptosis, immunogenic cell death, bacterial outer membrane vesicle  \nIntroduction  \nMost tumors remain difficult to treat due to their marked propensity for metastasis and relapse driven by intra-tumoral heterogeneity and tumor immune evasion [1] . A promising approach to prevent tumor metastasis and relapse is to induce immunogenic cell death (ICD) that simultaneously kills cancer cells and generates antitumor immune memory by evoking the dormant immune systems, which in turn determines  \nthe long-term success of anticancer therapies [2] . In clinical settings, most anticancer drugs rely on apoptosis, a form of programmed cell death that the body utilizes to decompose over a billion cells each day without inducing an immunostimulatory response, leaving the immune system in an “off” state [3] . While some chemotherapeutic drugs can induce excessive intracellular reactive oxygen species (ROS),  \nleading to calreticulin (CRT) translocation and making dying tumor cells immunogenic, the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) into th","cbCaitPDlXJlyNhi","https://ap.wps.com/l/cbCaitPDlXJlyNhi","pdf",15878077,24,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction\n## Immunogenic cell death and limits of apoptosis\n## Alternative cell death modalities and PANoptosis\n## Pyroptosis and non-canonical activation by OMVs","[{\"question\":\"What is the main goal of the CPApoptosis nano-actuator strategy?\",\"answer\":\"To convert immunologically cold (“immune-off”) solid tumors into an “immune-on” state by inducing multiple immunogenic cell death modalities and strengthening antitumor immune activation.\"},{\"question\":\"How were the therapeutic components prepared in this study?\",\"answer\":\"Elesclomol was encapsulated in bacterial outer membrane vesicles (OMVs), and the OMVs were surface-modified using Cu2+ and tannic acid via metal-phenolic self-assembly.\"},{\"question\":\"What mechanisms lead to tumor cell death and immune activation?\",\"answer\":\"The system releases Cu2+ and elesclomol in a pH-dependent manner, activating non-canonical pyroptosis, inducing cuproptosis via mitochondrial delivery, and promoting TA-mediated ROS production and oxidative apoptosis with GSH degradation; lysed tumor cells then release immunogenic factors that stimulate dendritic maturation and recruit cytotoxic T cells, further enhanced by αPD-L1 therapy.\"}]","CPApoptosis nano-actuator switches immune-off solid tumors to immune-on for fueling T-cell-based immunotherapy | PDF",1790216901]