{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T22:33:34Z","timestamp":1775601214061,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZR2022MH187"],"award-info":[{"award-number":["ZR2022MH187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["32101137"],"award-info":[{"award-number":["32101137"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Funct Materials"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\nIon interference including copper (Cu<jats:sup>+<\/jats:sup>)\/calcium (Ca<jats:sup>2+<\/jats:sup>) overload activate cell\u2010specific death channels, damage mitochondria and disrupt cellular homeostasis, showing great potential in anti\u2010tumor therapy. However, the complex metabolic environment and the powerful self\u2010protection of tumors cause clinical failure of ion interference. Thus, metabolic disruption is expected an innovative strategy for the enhancement of ion interference. Herein, CuS\u2010\u03b1\u2010CHCA&amp;penthiopyrad@CaCO<jats:sub>3<\/jats:sub>\u2010RGD nanoparticles (CCPCR NPs) are prepared to provide a Cu<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> dual\u2010overload anti\u2010tumor therapy assisted by metabolic\u2010symbiosis\u2010destruction strategy, realizing the collapse of tumor self\u2010protection. Specifically, precise CuS and CaCO<jats:sub>3<\/jats:sub> delivery triggered irreversible Cu<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> dual\u2010overload and reactive oxygen species (ROS) attack toward 4T1 cells. Meanwhile, \u03b1\u2010CHCA and penthiopyrad disturbed the metabolic symbiotic environment by disrupting the TCA cycle and preventing lactate efflux to aggravate intracellular acidosis and promote Fenton\u2010like reaction of Cu<jats:sup>+<\/jats:sup>, enhancing the sensitivity of tumor cells to copper death and Ca<jats:sup>2+<\/jats:sup> overload. Further, aided by the metabolism of symbiosis, the destroyed tumor cells further activate the polarization of M1 macrophages and the maturation and antigen cross\u2010presentation of dendritic cells (DCs), which further eliminate tumor cells. In summary, an amplified anti\u2010tumor dual\u2010ion interference strategy assisted by metabolic symbiotic destruction is established, which is of great significance in improving the clinical effect of ion therapy for tumors.<\/jats:p>","DOI":"10.1002\/adfm.202403245","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:09:22Z","timestamp":1716422962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cu<sup>+<\/sup>\/Ca<sup>2+<\/sup> Dual\u2010Overload Strategy Assisted by Metabolic\u2010Symbiotic\u2010Destruction for Tumor Apoptosis and Tumor Immune Activation"],"prefix":"10.1002","volume":"34","author":[{"given":"Jiahui","family":"Yan","sequence":"first","affiliation":[{"name":"Qingdao Municipal Hospital University of Health and Rehabilitation Sciences  Qingdao 266071 China"},{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Haoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Carlos F.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"3B's Research Group\u2010Research Institute on Biomaterials Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine University of Minho  Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra \u2013 Avepark, Barco Guimar\u00e3es 4805\u2010017 Portugal"},{"name":"ICVS\/3B's \u2013 Portuguese Government Associate Laboratory University of Minho Guimar\u00e3es\/Braga 4800\u2010058 Portugal"}]},{"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"3B's Research Group\u2010Research Institute on Biomaterials Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine University of Minho  Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra \u2013 Avepark, Barco Guimar\u00e3es 4805\u2010017 Portugal"},{"name":"ICVS\/3B's \u2013 Portuguese Government Associate Laboratory University of Minho Guimar\u00e3es\/Braga 4800\u2010058 Portugal"}]},{"given":"Zhihua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine Department Chengyang District People's Hospital  Qingdao 266100 China"}]},{"given":"Tianyi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Fenglan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Yaqian","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Qingdao Agricultural University  Qingdao 266100 China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-4197","authenticated-orcid":false,"given":"Qihui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation School of Rehabilitation Sciences and Engineering University of Health and Rehabilitation Sciences  Qingdao 266113 China"}]},{"given":"Xiaoying","family":"Kong","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Jinsheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Qingdao Municipal Hospital University of Health and Rehabilitation Sciences  Qingdao 266071 China"}]}],"member":"311","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2022.141227"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202300941"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2019.06.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo3959"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35515-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202205013"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202204733"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202008065"},{"key":"e_1_2_9_9_1","volume":"39","author":"Liu Z. 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