title: Use of biotin targeted methotrexate-human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy.
abstract: Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA) as a carrier. Methotrexate (MTX) molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs) were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-HSA NPs treatment at the same dose caused a body weight loss of 27.05% ± 3.1%.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Azade
authors.initials: A
authors.lastname: Taheri
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.forename: Faranak Salman
authors.initials: FS
authors.lastname: Nouri
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khorramizadeh
authors.forename: Atefeh Taheri
authors.initials: AT
authors.lastname: Borougeni
authors.forename: Pooria
authors.initials: P
authors.lastname: Mansoori
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001710:Biotin / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000008:administration & dosage*; D050997:Nanomedicine; D012709:Serum Albumin / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D012709:Serum Albumin; D001710:Biotin; D008727:Methotrexate