{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:41:59Z","timestamp":1785516119541,"version":"3.56.0"},"reference-count":46,"publisher":"Wiley","issue":"28","license":[{"start":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T00:00:00Z","timestamp":1690070400000},"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":["82003677"],"award-info":[{"award-number":["82003677"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82020108029"],"award-info":[{"award-number":["82020108029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073398"],"award-info":[{"award-number":["82073398"]}],"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":["ZR2020QH352"],"award-info":[{"award-number":["ZR2020QH352"]}],"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 Healthcare Materials"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> or relatively high pH value for Fenton reaction\u2010dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid\u2010based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction\u2010independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG<jats:sub>2K<\/jats:sub>\u2010DSPE\u2010modified liposomes (Lip@SF&amp;FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe<jats:sup>2+<\/jats:sup>, and subsequently the formed iron redox pair (Fe<jats:sup>2+<\/jats:sup>\/Fe<jats:sup>3+<\/jats:sup>) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction\u2010independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&amp;FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor\u2010killing ability with negligible side effect. Consequently, this two\u2010pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy.<\/jats:p>","DOI":"10.1002\/adhm.202301292","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T07:34:36Z","timestamp":1689579276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Synergistic Amplification of Ferroptosis with Liposomal Oxidation Catalyst and Gpx4 Inhibitor for Enhanced Cancer Therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Ye","family":"Yuan","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hulin","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifu","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3574-2357","authenticated-orcid":false,"given":"Yujing","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250117 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,23]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144908"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0720-y"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.2174\/1566523219666190628152137"},{"key":"e_1_2_8_2_4","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.6b04060"},{"key":"e_1_2_8_2_5","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202203085"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.10.086"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.02.009"},{"key":"e_1_2_8_3_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.10.014"},{"key":"e_1_2_8_4_1","first-page":"197","volume":"31","author":"Liang C.","year":"2019","journal-title":"Adv. Mater."},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201704007"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.01.034"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12274-021-3838-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b05042"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12274-021-3574-x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.118782"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.113413"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02536182"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.119911"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500235"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2022.112909"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00952-y"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2018.09.013"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00931-3"},{"key":"e_1_2_8_12_3","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202101926"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1705-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8TB01641K"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201810735"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.01.048"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2012.02.005"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2019.06.066"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2019.1580797"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-017-0277-2"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.11.001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12274-021-3595-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.121364"},{"key":"e_1_2_8_24_1","first-page":"6185","volume":"10","author":"Yao Y.","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8BM00381E"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2015.11.033"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.09.013"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NR02700E"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2013.01.016"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.13020"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0247-8_11"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2020.06.005"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202301292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:44:01Z","timestamp":1759751041000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202301292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,23]]},"references-count":46,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/adhm.202301292"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202301292","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,23]]},"assertion":[{"value":"2023-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2301292"}}