title: Targeted delivery of doxorubicin into tumor cells by nanostructured lipid carriers conjugated to anti-EGFRvIII monoclonal antibody.
abstract: Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the EGF receptor in many human tumors. This variant is tumor specific and highly immunogenic, thus, it can be used as a target for targeted drug delivery toward tumor cells. The major aim of this study was to develop an EGFRvIII-mediated drug delivery system by anti-EGFRvIII monoclonal antibody (MAb) conjugated to doxorubicin (Dox)-loaded nanostructured lipid carriers (NLC) to enhance the targeting specificity and cytotoxic effect of Dox on EGFRvIII-overexpressing cell line. In our study, Dox was chosen as a hydrophobic cytotoxic drug and drug-loaded nanostructured lipid carriers (Dox-NLC) was prepared by solvent emulsification/evaporation method. In order to conjugate anti-EGFRvIII MAb to Dox-NLC, DSPE-PEG2000-NHS (1,2-distearoylphosphatidylethanolamine-polyethylene glycol 2000-NHS) was used as a linker. Physicochemical characteristics of antibody conjugated Dox-NLC (MAb-Dox-NLC), including particle size, zeta potential, entrapment efficiency and in vitro Dox release were investigated. Cytotoxicity of MAb-Dox-NLC against NIH-3T3 and HC2 20d2/c (EGFRvIII-transfected NIH-3T3) cell lines was evaluated. The MAb-Dox-NLC appeared to enhance the cytotoxic activity of targeted NLC against HC2 20d2/c cells. The cellular uptake percentage of targeted NLC by HC2 20d2/c cells was higher than that of NIH-3T3 cells, indicating that EGFRvIII can specifically target HC2 20d2/c cells. In conclusion, anti-EGFRvIII MAb-targeted NLC may be considered as an effective nanocarrier for targeted drug delivery.
authors.affiliation: a Department of Medical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Saeideh
authors.initials: S
authors.lastname: Abdolahpour
authors.affiliation: b Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Toliyat
authors.affiliation: c Biosensor Research Center, Endocrinology and Metabolism Molecular and Cellular Sciences Institute, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Kobra
authors.initials: K
authors.lastname: Omidfar
authors.affiliation: d School of Life Science, Faculty of Science, Engineering and Computing, Kingston University , London.
authors.forename: Helmout
authors.initials: H
authors.lastname: Modjtahedi
authors.affiliation: e Brain Tumor Research Laboratories, Program in Cancer Biology, Stanford University Medical Center , Stanford , CA , USA.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Wong
authors.affiliation: f Department of Medical Biotechnology , School of Medical Sciences, Tarbiat Modarres University , Tehran , Iran.
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Rasaee
authors.affiliation: a Department of Medical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Susan
authors.initials: S
authors.lastname: Kashanian
authors.affiliation: a Department of Medical Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Paknejad
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D065546:Drug Liberation; D066246:ErbB Receptors / Q000276:immunology*; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008055:Lipids; C410723:epidermal growth factor receptor VIII; D011092:Polyethylene Glycols; D004317:Doxorubicin; D066246:ErbB Receptors; C000595210:polyethylene glycol 2000
keywords: Doxorubicin; EGFRvIII; NLC; cytotoxicity