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By camouflaging lung cancer cell membranes onto glucose oxidase-loaded Cu-LDHs, the system synergistically regulates PD-L1 expression through self-amplified cascade reactions, inducing cuproptosis and PD-L1 upregulation. In LLC lung tumor-bearing mice, it shows tumor targeting, biosafety, and strong anti-tumor efficacy, and combination dosing sensitizes αPD-L1 treatment to suppress both subcutaneous growth and lung metastasis.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-smart-nanomedicine-unleashes-a-dual-assault-of-glucose-starvation-and-cuproptosis-to-supercharge-pd-l1-therapy/332967/",{"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/a-smart-nanomedicine-unleashes-a-dual-assault-of-glucose-starvation-and-cuproptosis-to-supercharge-pd-l1-therapy/332967.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of this nanomedicine study?","Question",{"text":112,"@type":113},"To enhance the therapeutic outcomes of anti-PD-L1 treatment in lung cancer by linking glucose metabolism disruption and cuproptosis with immunotherapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the proposed system target cancer metabolism?",{"text":117,"@type":113},"It uses a biomimetic nano-delivery platform that camouflages lung cancer cell membranes on glucose oxidase-loaded Cu-LDHs to interfere with glucose and copper metabolism in tumor cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What benefits are reported in animal tumor models when combining with αPD-L1 therapy?",{"text":121,"@type":113},"Combination treatment with the nanomedicine sensitizes αPD-L1 effects, substantially improving tumor inhibition in both subcutaneous and lung metastasis LLC-bearing mice while maintaining biosafety.","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},332967,1790792694,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1794309523707217728","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nA Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge 􀀂PD-L1 Therapy  \nYiming Xu, Yuan Wu, Xinjie Zheng, Dongxue Wang, Hangqi Ni, Weiyu Chen,* and Kai Wang*  \nCombination therapy has become a promising strategy for promoting the outcomes of anti-programmed death ligand-1 (􀀂PD-L1) therapy in lung cancer. Among all, emerging strategies targeting cancer metabolism have shown great potency in treating cancers with immunotherapy. Here, alteration in glucose and copper metabolisms is found to synergistically regulate PD-L1 expression in lung cancer cells. Thus, an intelligent biomimetic nano-delivery system is synthesized by camouflaging lung cancer cell membranes onto glucose oxidase-loaded Cu-LDHs (CMGCL) for cancer metabolism targeted interference. Such novel nanomedicine is able to induce lung cancer cell cuproptosis and PD-L1 upregulation significantly via self-amplified cascade reactions. Meanwhile, with a decent cancer cell membrane coating, CMGCL exhibited great biosafety, tumor-targeted efficiency and anti-tumor effects in LLC lung tumor-bearing mice models. Additionally, a combination of CMGCL can sensitize the therapeutic effects of 􀀂PD-L1, substantially promoting tumor inhibition in both subcutaneous and lung metastasis LLC-bearing mice models. Overall, these findings highlight the potential connections between glucose metabolism and cell cuproptosis, offering a promising approach for treating lung cancer by integrating starvation, cuproptosis, and immunotherapy.  \n1. Introduction  \nTo date, lung cancer still contributes to most cancer-related deaths worldwide, with ≈2.4 million new diagnoses and 1.3 million fatalities reported annually.[1] Recently, immunotherapy, particularly immune checkpoint inhibitors (ICIs), has garnered significant attention due to the desirable therapeutic outcomes for most lung cancer patients. [2] For instance, the anti-programmed death ligand-1 (􀀂PD-L1) antibody, as one of the most widely used ICIs, has been approved for more than 20 types of solid tumors, including lung cancer. However, some patients respond poorly or generate resistance due to a shortage of PD-L1 expression and dysfunctional immune response within the tumor microenvironment (TME) . [2b,3] Moreover, similar to other traditional therapies (e.g., chemotherapy or radiotherapy), the accompanying side effects, such as immunerelated adverse effects (irAEs), also limit  \nY. Xu, X. Zheng, H. Ni, W. Chen, K. Wang Department of Respiratory and Critical Care Medicine Center for Oncology Medicine  \nThe Fourth Affiliated Hospital of School of Medicine and International School of Medicine  \nInternational Institutes of Medicine  \nZhejiang University  \nYiwu 322000, China  \n[E-mail:](E-mail: weiyuchen@zju.edu.cn)[ weiyuchen@zju.edu.cn](E-mail: weiyuchen@zju.edu.cn); [kaiw@zju.edu.cn](kaiw@zju.edu.cn)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202411378](https://doi.org/10.1002/advs.202411378)[ ](https://doi.org/10.1002/advs.202411378)© 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.  \nY. Xu, X. Zheng, H. Ni, W. Chen, K. Wang  \nZhejiang Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer  \nYiwu 322000, China Y. Wu  \nCollege of Jiyang Zhejiang A&F University Zhuji 311800, China  \nD. Wang  \nDepartment of Nuclear Medicine  \nThe Second Affiliated Hospital of Harbin Medical University Harbin 150000, China  \nDOI: 10.1002/advs.202411378  \nAdv. Sci. 2025, 12, 2411378 2411378 (1 of 15) © 2024 The Author(s) . Advanced Science published by Wiley-VCH GmbH  \n[www.advancedsciencenews.com](www.advancedsciencenews.com) [www.advancedscience.com](www.adv","cbCais7TUspyNkmh","https://ap.wps.com/l/cbCais7TUspyNkmh","pdf",7142303,15,"English","# Introduction\n## Immunotherapy and PD-L1 limitations\n## Rationale for metabolism-targeted combination strategies\n## Glucose starvation via glucose oxidase\n## Role of TCA cycle and copper in cancer cell death","[{\"question\":\"What is the main goal of this nanomedicine study?\",\"answer\":\"To enhance the therapeutic outcomes of anti-PD-L1 treatment in lung cancer by linking glucose metabolism disruption and cuproptosis with immunotherapy.\"},{\"question\":\"How does the proposed system target cancer metabolism?\",\"answer\":\"It uses a biomimetic nano-delivery platform that camouflages lung cancer cell membranes on glucose oxidase-loaded Cu-LDHs to interfere with glucose and copper metabolism in tumor cells.\"},{\"question\":\"What benefits are reported in animal tumor models when combining with αPD-L1 therapy?\",\"answer\":\"Combination treatment with the nanomedicine sensitizes αPD-L1 effects, substantially improving tumor inhibition in both subcutaneous and lung metastasis LLC-bearing mice while maintaining biosafety.\"}]","A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD-L1 Therapy | PDF",1790000193,38]