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Recently, a few nanoformulations based on polypeptides comprising NK105, NC6004, NK911, CT2103, have entered phase I-III clinical trials for advanced solid tumors therapy. In the current study, we prepared polypeptide-based vesicles called peptosome via self-assembly of amphiphilic polypeptide-based PEG-PBLG diblock copolymer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this regard, poly(\u03b3-benzyl L-glutamate (PBLG) was synthesized via ring opening polymerization (ROP) of \u03b3-benzyl L-glutamate-N-carboxyanhydride (BLG-NCA) using N-hexylamine as initiator. Then amine-terminated PBLG was covalently conjugated to heterofuctional maleimide PEG-carboxylic acid or methyl-PEG-carboxylic acid. The PEG-PBLG peptosomes were prepared through double emulsion method for the co-delivery of doxorubicin.HCl and gold nanorods as hydrophilic and hydrophobic agents in interior compartment and membrane of peptosomes, respectively (Pep@MUA.GNR-DOX) that DOX encapsulation efficiency and loading capacity were determined 42\u2009\u00b1\u20093.6 and 1.68\u2009\u00b1\u20093.6. Then, theranostic peptosomes were decorated with thiol-functionalized EpCAM aptamer throught thiol-maleimide reaction producing Apt-Pep@MUA.GNR-DOX for targeted delivery. The non-targeted and targeted peptosomes showed 165.5\u2009\u00b1\u20091.1 and 185\u2009\u00b1\u20094.7\u00a0nm diameters, respectively while providing sustained, controlled release of DOX. Furthermore, non-targeted and targeted peptosomes showed considerable serum stability. In vitro study on MCF-7 and 4T1 cells showed significantly higher cytotoxicity for Apt-Pep@MUA.GNR-DOX in comparison with Pep@MUA.GNR-DOX while both system did not show any difference in cytotoxicity against CHO cell line. Furthermore, Apt-Pep@MUA.GNR-DOX illustrated higher cellular uptake toward EpCAM-overexpressing 4T1 cells compared to Pep@MUA.GNR-DOX. In preclinical stage, therapeutic and diagnostic capability of the prepared Pep@MUA.GNR-DOX and Apt-Pep@MUA.GNR-DOX were investigated implementing subcutaneous 4T1 tumor model in BALB\/c mice. The obtained data indicated highest therapeutic index for Apt-Pep@MUA.GNR-DOX compared to Pep@MUA.GNR-DOX and free DOX. Moreover, the prepared system showed capability of CT imaging of tumor tissue in 4T1 tumorized mice through tumor accumulation even 24\u00a0h post-administration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In this regard, the synthesized theranostic peptosomes offer innovative hybrid multipurpose platform for fighting against breast cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12951-022-01607-2","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T11:02:43Z","timestamp":1661943763000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Synthesis of doxorubicin-loaded peptosomes hybridized\u00a0with gold nanorod for targeted drug delivery and CT imaging of metastatic breast cancer"],"prefix":"10.1186","volume":"20","author":[{"given":"Maliheh","family":"Hasannia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Abnous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Mohammad","family":"Taghdisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirous","family":"Nekooei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Ramezani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Alibolandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"issue":"32","key":"1607_CR1","doi-asserted-by":"publisher","first-page":"7166","DOI":"10.1039\/D0TB01175D","volume":"8","author":"AAP Mansur","year":"2020","unstructured":"Mansur AAP, et al. 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