title: Targeting of polyplex to human hepatic cells by bio-nanocapsules, hepatitis B virus surface antigen L protein particles.
abstract: We have previously demonstrated that lipoplex, a complex of cationic liposomes and DNA, could be targeted to human hepatic cells in vitro and in vivo by conjugation with bio-nanocapsules (BNCs) comprising hepatitis B virus (HBV) surface antigen L protein particles. Because the BNC-lipoplex complexes were endowed with the human hepatic cell-specific infection machinery from HBV, the complexes showed excellent specific transfection efficiency in human hepatic cells. In this study, we have found that polyplex (a complex of polyethyleneimine (PEI) and DNA) could form stable complexes with BNCs spontaneously. The diameter and ζ-potential of BNC-polyplex complexes are about 240 nm and +3.54 mV, respectively, which make them more suitable for in vivo use than polyplex alone. BNC-polyplex complexes with an N/P ratio (the molar ratio of the amine group of PEI to the phosphate group of DNA) of 40 showed excellent transfection efficiency in human hepatic cells. When acidification of endosomes was inhibited by bafilomycin A1, the complexes showed higher transfection efficiency than polyplex itself, strongly suggesting that the complexes escaped from endosomes by both fusogenic activity of BNCs and proton sponge activity of polyplex. Furthermore, the cytotoxicity is comparable to that of polyplex of the same N/P value. Thus, BNC-polyplex complexes would be a promising gene delivery carrier for human liver-specific gene therapy.
authors.affiliation: Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Somiya
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yoshimoto
authors.forename: Masumi
authors.initials: M
authors.lastname: Iijima
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Niimi
authors.forename: Takehisa
authors.initials: T
authors.lastname: Dewa
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D011992:Endosomes / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006514:Hepatitis B Surface Antigens / Q000737:chemistry* / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D006514:Hepatitis B Surface Antigens; D018942:Macrolides; C040929:bafilomycin A1; D011094:Polyethyleneimine; D004247:DNA