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However, nanotechnology provides new innovative therapeutic strategies. This study evaluates the efficacy of new HER2\u2010targeted, pH\u2010sensitive poly(ethylene glycol)\u2010poly(L\u2010histidine) copolymer micelles (PEG\u2010PHis micelles), either empty, loaded with the drug doxorubicin (DOX), or the fluorophore Rhodamine\u2010B (RB) for imaging purposes. Cellular association of the micelles, in vitro effects on proliferation and cytotoxicity, as well as ex vivo and in vivo responses on tumor growth are assessed. The results indicate that trastuzumab (TZM) conjugation enhances the specific cellular association of PEG\u2010PHis micelles in HER2 overexpressing cells and improves the cytotoxic effects of the micelles themselves. Although the TZM conjugation of DOX\u2010loaded micelles did not contribute to an enhancement in overall efficacy in cell lines and tumor explant cultures, the findings highlight the potential of TZM conjugation on these micelles in targeting HER2\u2010positive tumors.<\/jats:p>","DOI":"10.1002\/mabi.202500047","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:49:31Z","timestamp":1753699771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of HER2 Targeted Poly(Ethylene Glycol)\u2010Poly(\n                    <i>L<\/i>\n                    \u2010histidine) Copolymer Micelles in Breast Cancer Models"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8064-4268","authenticated-orcid":false,"given":"Remya","family":"Valsala Kumari","sequence":"first","affiliation":[{"name":"Department of Tumor Biology Institute For Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Department of Molecular Cell Biology Institute For Cancer Research Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7713-3050","authenticated-orcid":false,"given":"Abhilash D.","family":"Pandya","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology Institute For Cancer Research Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5360-1292","authenticated-orcid":false,"given":"Solveig J.","family":"Pettersen","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology Institute For Cancer Research Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-2247","authenticated-orcid":false,"given":"Audun","family":"Kvalvaag","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Institute For Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Centre For Cancer Cell Reprogramming University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Grethe","family":"Myrann","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Institute For Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Centre For Cancer Cell Reprogramming University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6540-9163","authenticated-orcid":false,"given":"Razvan","family":"Ghiarasim","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers \u201cPetru Poni\u201d Institute of Macromolecular Chemistry  Iasi Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-9515","authenticated-orcid":false,"given":"Alexandru","family":"Rotaru","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers \u201cPetru Poni\u201d Institute of Macromolecular Chemistry  Iasi Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihail\u2010Gabriel","family":"Dimofte","sequence":"additional","affiliation":[{"name":"Regional Institute of Oncology  Iasi Romania"},{"name":"University of Medicine and Pharmacy \u201cGrigore T. 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