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Herein, we developed a dual-action nanoformulation combining prolinium-based surface-active ionic liquid (SAIL) nanocarriers with ErbB2-derived transmembrane (TM) peptide for selective targeting of ErbB2-positive cancer cells. Two new SAILs, which self-assemble into stable micelles\/vesicles under physiological conditions, and a series of hydrophobic TM-peptides were synthesized and characterized. Among the resulting nanoformulations, V3-BAIL showed the strongest antiproliferative activity in ErbB2-positive breast, lung, and pancreatic cancer cell lines, whereas activity in low-ErbB2 NCl-H23 cells was minimal. The response correlated with ErbB2 expression level, demonstrating target-related selectivity. Chou-Talalay analysis revealed synergy between the SAIL nanocarrier and TM peptide. Mechanistic studies showed that V3-BAIL progressively accumulated in cells, reduced cellular fitness without rapid membrane lysis, and strongly suppressed PI3K\/Akt and MAPK\/ERK signaling. Relative to doxorubicin and cisplatin, V3-BAIL displayed greater selectivity toward ErbB2-positive cells, and it acted more rapidly and more strongly than trastuzumab under the tested conditions. These findings establish TM peptide-decorated SAIL nanocarriers as a promising strategy for selective and synergistic ErbB2-targeted cancer therapy.<\/jats:p>","DOI":"10.1021\/acsami.6c08450","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:01:29Z","timestamp":1787162489000},"page":"46007-46021","source":"Crossref","is-referenced-by-count":0,"title":["Selective and Synergistic Targeting of ErbB2-Positive Cancer Cells with ErbB2 Transmembrane Peptide-Ionic Liquid Nanocarrier Formulation"],"prefix":"10.1021","volume":"18","author":[{"given":"Helal","family":"Abujubara","sequence":"first","affiliation":[{"name":"University of Gothenburg , , Natrium, Medicinaregatan 7B , ,","place":["Gothenburg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]},{"name":"Al-Ahliyya Amman University , , ,","place":["Amman, Jordan, 19328"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-0475","authenticated-orcid":true,"given":"Pankaj","family":"Bharmoria","sequence":"additional","affiliation":[{"name":"Institute of Materials Science of Barcelona, ICMAB-CSIC , , ,","place":["Bellaterra, Barcelona, Spain, 08193"]},{"name":"Universitat Polit\u00e8cnica de Catalunya, EEBE , , Eduard Maristany 10\u201314 , ,","place":["Barcelona, Spain, 08019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Raj","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Medicinaregatan 1F , ,","place":["G\u00f6teborg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha W.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Medicinaregatan 1F , ,","place":["G\u00f6teborg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Natrium, Medicinaregatan 7B , ,","place":["Gothenburg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryna","family":"Zhylinskaya","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Natrium, Medicinaregatan 7B , ,","place":["Gothenburg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enoch","family":"Appiah","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Natrium, Medicinaregatan 7B , ,","place":["Gothenburg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-4927","authenticated-orcid":true,"given":"Kasper","family":"Moth-Poulsen","sequence":"additional","affiliation":[{"name":"Institute of Materials Science of Barcelona, ICMAB-CSIC , , ,","place":["Bellaterra, Barcelona, Spain, 08193"]},{"name":"Universitat Polit\u00e8cnica de Catalunya, EEBE , , Eduard Maristany 10\u201314 , ,","place":["Barcelona, Spain, 08019"]},{"name":"Catalan Institution for Research & Advanced Studies, ICREA , Pg. Llu\u00eds Companys 23 , ,","place":["Barcelona, Spain, 08010"]},{"name":"Chalmers University of Technology , , ,","place":["Gothenburg, Sweden, 41296"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clotilde","family":"Wiel","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Medicinaregatan 1F , ,","place":["G\u00f6teborg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkan I.","family":"Sayin","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Medicinaregatan 1F , ,","place":["G\u00f6teborg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9281-548X","authenticated-orcid":true,"given":"Alesia A.","family":"Tietze","sequence":"additional","affiliation":[{"name":"University of Gothenburg , , Natrium, Medicinaregatan 7B , ,","place":["Gothenburg, Sweden, 41390"]},{"name":"University of Gothenburg , , ,","place":["Gothenburg, Sweden, 41390"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026101216063443300_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.103915","article-title":"Monoclonal Antibodies in Breast Cancer: A Critical Appraisal","volume":"183","author":"Behl","year":"2023","journal-title":"Crit. 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