{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T09:58:44Z","timestamp":1767607124855,"version":"3.48.0"},"reference-count":44,"publisher":"Wiley","issue":"45","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibody\u2013drug conjugates (ADCs) have transformed cancer therapy but remain limited by their dependence on internalizing antigens, poor applicability to untargetable tumors, and susceptibility to drug resistance. Therefore, a modular antimicrobial\u2010peptide (AMP)\u2010based therapeutic system centered on a rationally designed conjugate, 270, is presented, which integrates three optimized components: a selectivity\u2010enhanced AMP core via a membrane affinity reconstruction strategy, a conformation\u2010driven polyethylene glycolylated blocker to minimize off\u2010target effects, and an N\u2010terminal cap to improve stability in human serum. By targeting nonendocytic membrane surface receptors via small\u2010molecule ligands, conjugate 270 exhibits potent and selective cytotoxicity against target tumor cells, effectively eliminating the majority of tumor cells within a few hours. Meanwhile, it exhibits high serum stability, minimal hemolysis, and negligible cytotoxicity toward normal cells at therapeutic concentrations. Mechanistic studies confirm ligand\u2010dependent membrane localization, rapid depolarization, and disruption, along with mitochondrial dysfunction. Moreover, it demonstrates significant therapeutic efficacy against four cell lines resistant to conventional chemotherapeutic agents. While additional in vivo validation is warranted, this work lays the foundation for a flexible AMP\u2010based approach to address untargetable and drug\u2010resistant cancers.<\/jats:p>","DOI":"10.1002\/advs.202504710","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T08:55:26Z","timestamp":1758099326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Serum\u2010Stable Antimicrobial Peptide\u2010Based Delivery Platform for Selective Treatment of Nontargetable and Chemoresistant Tumors"],"prefix":"10.1002","volume":"12","author":[{"given":"Tianxing","family":"Liu","sequence":"first","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyu","family":"Ke","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruize","family":"Sun","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6783-4160","authenticated-orcid":false,"given":"Xiaoling","family":"Chen","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf R. P.","family":"Bininda\u2010Emond","sequence":"additional","affiliation":[{"name":"AG Systematik und Evolutionsbiologie IBU\u2010Faculty V Carl von Ossietzky University Oldenburg  26111 Oldenburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbang","family":"Ma","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Shaw","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianbao","family":"Chen","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group School of Pharmacy Queen's University Belfast Belfast Northern Ireland BT71NN UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alideertu","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Engineering Research Center of Dairy Quality and Safety Control Technology Ministry of Education Inner Mongolia University  235 Daxue West Road Hohhot 010021 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00709-2"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00850-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017-0604"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00947-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32417-5"},{"key":"e_1_2_8_6_1","volume":"3","author":"Greenhalgh J.","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-22-0013"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02679-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00729C"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-022-01848-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712801661004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121076"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114557"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.2420"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.71129"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.5c00123"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2016.01.003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1515\/jtim-2024-0019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmab126"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318258cf17"},{"key":"e_1_2_8_21_1","first-page":"1081","volume":"26","author":"Wang J.","year":"2011","journal-title":"Oncol. Rep."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21510"},{"key":"e_1_2_8_23_1","volume":"15","author":"Wang Z.","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19960901)25:1<14::AID-CYTO2>3.0.CO;2-E"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104573"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12889"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5b08637"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.02.114"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-80540-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6807-14-4"},{"key":"e_1_2_8_31_1","first-page":"795","volume":"26","author":"Sanderink G. J.","year":"1988","journal-title":"J. Clin. Chem. Clin. Biochem."},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2006.191"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1819258"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.3306"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi971705p"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp025575s"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030795v"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.1999.00462.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29030655"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.18332\/pht\/197414"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-017-2757-8"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216669"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-021-00799-4"},{"key":"e_1_2_8_44_1","first-page":"288","volume":"12","author":"Dong X. D.","year":"2024","journal-title":"J. Transl. Intern. Med."}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202504710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T09:56:52Z","timestamp":1767607012000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202504710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":44,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/advs.202504710"],"URL":"https:\/\/doi.org\/10.1002\/advs.202504710","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"type":"print","value":"2198-3844"},{"type":"electronic","value":"2198-3844"}],"subject":[],"published":{"date-parts":[[2025,9,17]]},"assertion":[{"value":"2025-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04710"}}