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Peptide\u2010drug conjugates (PDCs) offer a structurally precise and bio\u2010programmable strategy to compensate for these drawbacks. Herein, we report a structurally precise platinum (Pt)\u2010based PDC design that integrates axial\u2010ligand engineering with carrier\u2010free self\u2010assembly. Axial covalent modification of Pt\n                    <jats:sup>IV<\/jats:sup>\n                    with a hydrophobic alkyl chain and a cyclic RGD targeting peptide (c(RGD)fk) affords a structurally well\u2010defined amphiphilic prodrug that spontaneously assembles into stable lipid nanoparticles (NPt\n                    <jats:sup>IV<\/jats:sup>\n                    cRGD). These nanoparticles exhibited high\n                    <jats:italic>\n                      \u03b1\n                      <jats:sub>v<\/jats:sub>\n                      \u03b2\n                      <jats:sub>3<\/jats:sub>\n                    <\/jats:italic>\n                    integrin\u2010mediated selectivity, resulting in superior tumor accumulation. Within the reductive tumor microenvironment, the Pt\n                    <jats:sup>IV<\/jats:sup>\n                    center was converted to cytotoxic Pt\n                    <jats:sup>II<\/jats:sup>\n                    , resulting in pronounced DNA damage and a tumor growth inhibition rate of 78%, significantly outperforming cisplatin. Notably, systemic toxicity was markedly attenuated, as evidenced by minimal body weight loss and reduced hepatic and renal damage. This study establishes a structurally simplified PDC\u2010based chemotherapy paradigm for Pt drugs. By axially functionalizing a Pt\n                    <jats:sup>IV<\/jats:sup>\n                    prodrug with an active targeting peptide and leveraging its carrier\u2010free self\u2010assembly properties, this approach enhances antitumor efficacy while significantly minimizing off\u2010target toxicity.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71306","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:10:26Z","timestamp":1780117826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Self\u2010Assembly of Peptide\u2010Lipid Platinum(IV) Prodrug Amphiphile for \u03b1v\u03b23 Integrin\u2010Targeting Chemotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiaolu","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaichuang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9713-028X","authenticated-orcid":false,"given":"Dengshuai","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201043718\u2010w"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202308251"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.02.013"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.07.020"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2025.09.968"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102025\u20102550"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010022\u201001274\u20108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.AM2025\u20105646"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010025\u201001704\u20103"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2024.154169"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr8841"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2025.06.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202500645"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c15759"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.AM2025\u2010586"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae859"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.22046"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2025.07.029"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.AM2025\u20101761"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202518980"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202500996"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c18243"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201047842\u2010z"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049675\u20102"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2024.215774"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2023.215578"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202506011"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2025.216808"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c12706"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202401397"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.01.001"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010025\u201001000\u20106"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c12447"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114195"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113835"}],"container-title":["Advanced 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