title: The in vivo antitumor activity of LHRH targeted methotrexate-human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice.
abstract: The use of targeted drug delivery systems is a growing trend in cancer treatment to decrease the adverse effect of anti-cancer drugs. In this study, we sought to conjugate methotrexate-human serum albumin nanoparticles (MTX-HSA NPs) with luteinizing-hormone releasing hormone (LHRH). The LHRH was intended to target LHRH receptors overexpressed on the several types of tumors. The expression of LHRH receptors on the 4T1 breast cancer cells was confirmed by FITC conjugated LHRH receptor antibody using fluorescence microscopy. Female Balb/c mice bearing 4T1 breast cancer tumor were treated with a single i.v. injection of free MTX, non-targeted MTX-HSA NPs and LHRH targeted MTX-HSA NPs. LHRH targeted MTX-HSA nanoparticles showed stronger anti-tumor activity in vivo. By 7 days after treatment, average tumor volume in the LHRH targeted MTX-HSA NPs treated group decreased to 8.67% of the initial tumor volume when the number of attached LHRH molecules on MTX-HSA NPs was the highest, while the average tumor volume in non-targeted MTX-HSA NPs treated mice grew rapidly and reached 250.7% of the initial tumor volume 7 days after the treatment. LHRH targeted MTX-HSA NPs could significantly extend the survival time of tumor bearing mice compared with the non-targeted MTX-HSA NPs and free MTX formulations.
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: Fatemeh
authors.initials: F
authors.lastname: Ahadi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khorramizadeh
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012709:Serum Albumin / Q000008:administration & dosage*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D012709:Serum Albumin; C040811:methotrexate-serum albumin; D007987:Gonadotropin-Releasing Hormone; D008727:Methotrexate