{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:54:27Z","timestamp":1792742067982,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"32","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cuproptosis, an emerging form of programmed cell death, is capable of inducing mitochondrial dysfunction. Moreover, the PI3K\u2010AKT\u2010mTOR signaling pathway contributes to tumor cell progression by reprogramming mitochondrial morphology and function. In this study, we have designed copper complex nanoparticles (NP\n                    <jats:sup>Cu<\/jats:sup>\n                    ) and PI3K\u2010AKT\u2010mTOR inhibitor Alpelisib nanoparticles (NP\n                    <jats:sup>ALP<\/jats:sup>\n                    ) that enhance the efficacy of cuproptosis\u2010based therapies. NP\n                    <jats:sup>Cu<\/jats:sup>\n                    triggers mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S\u2010acetyltransferase (DLAT), while NP\n                    <jats:sup>ALP<\/jats:sup>\n                    inhibits the PI3K\u2010AKT\u2010mTOR signaling pathway to induce apoptosis. The combination of these two nanoparticles (NP\n                    <jats:sup>Cu<\/jats:sup>\n                    +NP\n                    <jats:sup>ALP<\/jats:sup>\n                    ) effectively activates the antitumor responses in the tumor microenvironment (TME). When combined with an anti\u2010programmed cell death protein 1 antibody (\u03b1\u2010PD\u20101), NP\n                    <jats:sup>Cu<\/jats:sup>\n                    +NP\n                    <jats:sup>ALP<\/jats:sup>\n                    significantly inhibits tumor progression and activates antitumor immunity, offering a promising strategy for liver cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202506051","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:37:37Z","timestamp":1778009857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["GSH\u2010Responsive Nanoparticles Enhance Hepatocellular Carcinoma Immunotherapy Through Synergistic Effects of Cuproptosis and PI3K Inhibitor Combination"],"prefix":"10.1002","volume":"13","author":[{"given":"Lei","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintong","family":"Na","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences  Beijing P. R. China"},{"name":"University of Chinese Academy of Sciences  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhungang","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihua","family":"Xiao","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences  Beijing P. R. China"},{"name":"University of Chinese Academy of Sciences  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2214-5887","authenticated-orcid":false,"given":"Yongxiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Bio\u2010targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development Guangxi Medical University  Nanning Guangxi P. R. China"},{"name":"Targeting Theranostics Research Center of Guangxi Higher Education Guangxi Medical University  Nanning Guangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01229-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000417\u20102"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf0529"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010022\u201000866\u20101"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010023\u201001125\u20100"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2020.213474"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01392-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010022\u201002485\u20100"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.3c00434"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010024\u201000876\u20100"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06264-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005678\u20103"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00160"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02437-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602751113"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202212267"},{"key":"e_1_2_9_18_1","article-title":"Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy","volume":"11","author":"Lu X.","year":"2024","journal-title":"Advancement of Science"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00522-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04206-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114183"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.34133\/bmef.0016"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.34133\/bmef.0015"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.34133\/bmef.0012"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2023.12.019"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202203820"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010021\u201000728\u20107"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12645-014-0008-4"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050020\u2010w"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202406815"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116892"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202305668"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010024\u201000920\u20109"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3380"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00417D"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202310298"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01658-3"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202403116"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202408481"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add2712"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c12706"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035469\u2010x"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010024\u201001961\u20103"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.08.013"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202506051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202506051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202506051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:43:56Z","timestamp":1781527436000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202506051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":43,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/advs.202506051"],"URL":"https:\/\/doi.org\/10.1002\/advs.202506051","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"2025-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e06051"}}