{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:08:11Z","timestamp":1792033691457,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Libyan Government","award":["N\/a"],"award-info":[{"award-number":["N\/a"]}]},{"DOI":"10.13039\/501100004482","name":"Kuwait University","doi-asserted-by":"publisher","award":["N\/a"],"award-info":[{"award-number":["N\/a"]}],"id":[{"id":"10.13039\/501100004482","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014733","name":"Middle East University","doi-asserted-by":"publisher","award":["N\/a"],"award-info":[{"award-number":["N\/a"]}],"id":[{"id":"10.13039\/501100014733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000377","name":"Vivensa Foundation","doi-asserted-by":"publisher","award":["R463\/0216"],"award-info":[{"award-number":["R463\/0216"]}],"id":[{"id":"10.13039\/501100000377","id-type":"DOI","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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Docetaxel is a widely used chemotherapeutic agent for several malignancies and is an established treatment for castration-resistant prostate cancer. However, its poor aqueous solubility, systemic toxicity, and the emergence of drug resistance limit its clinical benefit. Zein, a prolamin, forms micelles that enhance the solubility and delivery of hydrophobic drugs. As PEG length and ligand presentation govern micelle behavior, we investigated transferrin-functionalized PEGylated zein micelles as docetaxel nanocarriers and examined how PEG chain length (5 K vs. 10 K) and transferrin-mediated targeting affect delivery to prostate cancer cells. Methods: Docetaxel-loaded zein micelles bearing 5 K or 10 K PEG chains were prepared and conjugated to transferrin. Formulations were characterized for size, charge, morphology, critical micelle concentration, colloidal stability, drug loading and transferrin density. Cellular uptake and mechanisms were assessed in PC-3-Luc, DU145 and LNCaP cells by confocal microscopy, flow cytometry and pharmacological inhibition. Anti-proliferative activity was determined by MTT assays. Results: Both PEG5K and PEG10K micelles formed micellar dispersions with low polydispersity and high encapsulation efficiency. PEG5K micelles achieved higher transferrin conjugation and drug loading. Transferrin-functionalized PEG5K micelles showed enhanced uptake in DU145 and LNCaP cells but lower internalization in PC-3-Luc cells. Inhibitor studies indicated receptor-dependent uptake via clathrin- and caveolae-mediated endocytosis. Free docetaxel remained the most potent. However, among nanocarriers, transferrin-targeted PEG5K micelles showed the greatest anti-proliferative efficacy relative to their non-targeted counterparts, whereas transferrin-targeted PEG10K micelles were less potent than the non-targeted PEG10K micelles across all three cell lines. Conclusions: PEG chain length and ligand presentation are key determinants of uptake and cytotoxicity of docetaxel-loaded zein micelles. Shorter PEG chains favor effective transferrin display and receptor engagement, whereas longer PEG likely induces steric hindrance and reduces targeting, supporting transferrin-conjugated PEG5K zein micelles (the lead formulation in this study) as a targeted delivery platform that improves performance relative to matched non-targeted micelles in vitro, while free docetaxel remains more potent in 2D monolayer assays.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010068","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PEGylated Zein Micelles for Prostate Cancer Therapy: Influence of PEG Chain Length and Transferrin Targeting on Docetaxel Delivery"],"prefix":"10.3390","volume":"18","author":[{"given":"Khadeejah","family":"Maeyouf","sequence":"first","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":"Jitkasem","family":"Meewan","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\/0009-0000-6177-7436","authenticated-orcid":false,"given":"Hawraa","family":"Ali-Jerman","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK"},{"name":"College of Pharmacy, Health Sciences Centre, Kuwait University, Jabriya P.O. Box 12345, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9411-4912","authenticated-orcid":false,"given":"Musa","family":"Albatsh","sequence":"additional","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"}]},{"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":"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":"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"}]},{"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","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\/0000-0002-7963-6364","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":[[2026,1,4]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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