{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:42Z","timestamp":1786115622500,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014733","name":"Middle East University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014733","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/059bgad73","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008078","name":"University of Strathclyde","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008078","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00n3w3b69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007287","name":"Worldwide Cancer Research","doi-asserted-by":"publisher","award":["16-1303"],"award-info":[{"award-number":["16-1303"]}],"id":[{"id":"10.13039\/501100007287","id-type":"DOI","asserted-by":"publisher"}]},{"award":["16-1303"],"award-info":[{"award-number":["16-1303"]}],"id":[{"id":"https:\/\/ror.org\/031tfbz57","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000377","name":"Dunhill Medical Trust","doi-asserted-by":"publisher","award":["R463\/0216"],"award-info":[{"award-number":["R463\/0216"]}],"id":[{"id":"10.13039\/501100000377","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R463\/0216"],"award-info":[{"award-number":["R463\/0216"]}],"id":[{"id":"https:\/\/ror.org\/05ayqqv15","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Advanced prostate cancer remains difficult to treat because docetaxel, although clinically important, is limited by systemic toxicity, poor tumor selectivity, and acquired resistance. Camptothecin is a potent anticancer agent, but its clinical application is restricted by poor solubility and instability. This study investigated the synergy between docetaxel and camptothecin and developed transferrin-conjugated, camptothecin-bearing dendrimersomes entrapping docetaxel as a targeted nanocarrier for prostate cancer therapy. Methods: Drug synergy was evaluated in PC3-Luc cells using an MTT assay and combination index analysis. Transferrin-conjugated, disulfide-linked camptothecin-bearing PEGylated DAB dendrimers were synthesized and characterized by 1H-NMR, critical aggregation concentration analysis, transmission electron microscopy, and entrapment efficiency measurements. pH- and redox-dependent drug release was assessed by dialysis. Cellular uptake and uptake mechanisms were investigated by confocal microscopy, flow cytometry, and inhibitor studies in PC3-Luc, DU145, and LNCaP cells. Anti-proliferative efficacy was determined by an MTT assay. Results: Docetaxel and camptothecin showed marked synergy in PC3-Luc cells, with a minimum combination index of 0.20 \u00b1 0.01 and 88.10 \u00b1 0.41% growth inhibition at low nanomolar concentrations. Transferrin-conjugated dendrimersomes self-assembled into spherical vesicles with a critical aggregation concentration of approximately 250 \u00b5g\/mL. They had high docetaxel entrapment efficiency (89.10 \u00b1 0.08%) and enhanced drug release under acidic and reductive conditions. They significantly increased cellular uptake of docetaxel relative to non-targeted dendrimersomes (by up to 3-fold) and free drugs (by up to 20-fold), mainly through transferrin receptor-mediated endocytosis, and improved anti-proliferative activity in all three cell lines. Tf-conjugated DPSSC produced the lowest IC50 values among the tested formulations: 11.72 \u00b1 1.02 nM in PC3-Luc, 9.88 \u00b1 1.22 nM in DU145, and 7.88 \u00b1 1.35 nM in LNCaP cells. Conclusions: Transferrin-conjugated camptothecin-based dendrimersomes entrapping docetaxel represent a promising multifunctional nanocarrier for prostate cancer that combines synergistic dual-drug therapy, active targeting, and stimulus-responsive release, supporting further evaluation as a selective delivery strategy in advanced prostate cancer using preclinical models and in vivo studies.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080959","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:08:09Z","timestamp":1785856089000},"page":"959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transferrin-Conjugated, Camptothecin-Bearing Dendrimersomes Entrapping Docetaxel as a Dual-Drug Nanoplatform for Targeted Prostate Cancer Therapy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9411-4912","authenticated-orcid":false,"given":"Musa","family":"Albatsh","sequence":"first","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"},{"name":"Faculty of Pharmacy, Middle East University, Queen Aliaa Airport Street, Amman 11610, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8335-330X","authenticated-orcid":false,"given":"Zainab","family":"Al-Quraishi","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha","family":"Laskar","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"},{"name":"Department of Chemistry, School of Science, Gandhi Institute of Technology and Management, Visakhapatnam 530045, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukrut","family":"Somani","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Irving","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme R.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3798-2074","authenticated-orcid":false,"given":"Stuart","family":"Woods","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"},{"name":"School of Health and Life Sciences, University of the West of Scotland, Paisley Campus, High Street, Paisley PA1 2BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0653-835X","authenticated-orcid":false,"given":"Craig W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Mullin","sequence":"additional","affiliation":[{"name":"Cell Analysis Facility, Medical and Veterinary & Life Sciences Shared Research Facilities, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-6364","authenticated-orcid":false,"given":"Christine","family":"Duf\u00e8s","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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