title: Design of a dual-ligand system using a specific ligand and cell penetrating peptide, resulting in a synergistic effect on selectivity and cellular uptake.
abstract: In this study, a dual-ligand liposomal system comprised of a specific ligand and a cell penetrating peptide (CPP) is described to enhance selectivity and cellular uptake. Dual-ligand PEGylated liposomes were prepared by modifying the end of the PEG with an NGR motif peptide, followed by a surface coating of the liposomes with stearylated oligoarginine (STR-RX). The NGR motif recognizes CD13, a marker protein located on tumor endothelial cells. A suitable number of RX units was determined to be R4, since it can be masked by the PEG aqueous layer. Although no enhanced cellular uptake was observed when a single modification of PEGylated liposomes with either NGR- or STR-R4 was used, the dual-modification with NGR and STR-R4 stimulated uptake of PEGylated liposomes by CD13 positive cells, and this uptake was superior to that obtained by PEG-unmodified liposomes modified with STR-R4. The dual-ligand system shows a synergistic effect on cellular uptake. Collectively, the dual-ligand system promises to be useful in the development efficient and specific drug delivery systems.
authors.affiliation: Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takara
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatakeyama
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D001692:Biological Transport; D018826:CD13 Antigens / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D042783:Endothelial Cells / Q000378:metabolism*; D008024:Ligands; D008081:Liposomes; D008545:Melanoma / Q000098:blood supply*; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013228:Stearates / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; C526428:NGR peptide; D009842:Oligopeptides; D013228:Stearates; D011092:Polyethylene Glycols; D001120:Arginine; D018826:CD13 Antigens