title: Novel tocotrienol-entrapping vesicles can eradicate solid tumors after intravenous administration.
abstract: The therapeutic potential of tocotrienol, a vitamin E extract with anti-cancer properties, is hampered by its failure to specifically reach tumors after intravenous administration. In this work, we demonstrated that novel transferrin-bearing, tocopheryl-based multilamellar vesicles entrapping tocotrienol significantly improved tocotrienol uptake by cancer cells overexpressing transferrin receptors. This led to a dramatically improved therapeutic efficacy in vitro, ranging from 17-fold to 72-fold improvement depending on the cell lines, compared to the free drug. In vivo, the intravenous administration of this novel tocotrienol formulation led to complete tumor eradication for 40% of B16-F10 murine melanoma tumors and 20% of A431 human epidermoid carcinoma tumors. Animal survival was improved by more than 20 days compared to controls, for the two tumor models tested. These therapeutic effects, together with the lack of toxicity, potentially make transferrin-bearing vesicles entrapping tocotrienol a highly promising therapeutic system as part as an anti-cancer therapeutic strategy.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
authors.forename: Ju Yen
authors.initials: JY
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: David R
authors.initials: DR
authors.lastname: Blatchford
authors.forename: Laurence
authors.initials: L
authors.lastname: Tetley
authors.forename: Gail
authors.initials: G
authors.lastname: McConnell
authors.forename: Christine
authors.initials: C
authors.lastname: Dufès
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001692:Biological Transport; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000378:metabolism; D013499:Surface Properties; D016019:Survival Analysis; D024508:Tocotrienols / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D014168:Transferrin / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011990:Receptors, Transferrin; D024508:Tocotrienols; D014168:Transferrin