title: Nanoparticles electrostatically coated with folic acid for effective gene therapy.
abstract: We developed a novel vector, electrostatically coated poly(ethylenimine) (PEI)/pDNA complexes with folic acid (FA). Without covalent binding, the FA molecules could coat the PEI/pDNA complexes, and stable anionic nanoparticles were formed at a charge ratio greater than 60. The addition of FA markedly decreased the cytotoxicity of the cationic PEI/pDNA complexes to the melanoma cell line, B16-F10 cells, which regularly expressed FA-specific receptor (FR). Furthermore, the anionic FA60/PEI/pDNA complexes showed high transgene efficiency via the FR-mediated pathway in B16-F10 cells. The FA60/PEI/pDNA complexes did not show agglutination with erythrocytes. After the intravenous injection of FA60/PEI/pDNA complexes into mice, a higher transgene efficiency than PEI/pDNA complexes was observed in the liver, kidney, spleen, and lung with FR. The gene expressions of FA60/PEI/pDNA complexes were significantly inhibited by preadministration of FA. Thus, the FA60/PEI/pDNA complexes were useful for effective gene therapy.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Tamami
authors.initials: T
authors.lastname: Morishita
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Kayoko
authors.initials: K
authors.lastname: Sato
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005492:Folic Acid / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D011094:Polyethyleneimine; D005492:Folic Acid