title: In vivo tumor targeting of ODN-PEG-folic acid/PEI polyelectrolyte complex micelles.
abstract: A tumor-targeting antisense oligodeoxynucleotide (ODN) delivery system based on polyelectrolyte complex (PEC) micelles is demonstrated. ODN-PEG-folic acid (ODN-PEG-FA) was synthesized using a heterofunctional PEG linker. The PEC micelles for the targeted ODN delivery to tumor cells were produced by ionic interactions between the ODN-PEG-FA and polyethylenimine (PEI). The in vivo targeting properties of the PEC micelles were assessed using a mouse tumor model. The size of ODN-PEG-FA/PEI PEC micelles was 92.3 nm with a relatively narrow distribution. Cellular uptake of the ODN-PEG-FA/PEI PEC micelles by folic acid receptor over-expressing cells (KB) was greatly enhanced compared to that of ODN-PEG/PEI PEC micelles. When the ODN-PEG-FA/PEI PEC micelles were systemically administered to the mice bearing KB cell xenograft tumor, ODN was accumulated to the solid tumor in a target specific manner. This study suggests that the PEC micelles with a receptor-recognizable targeting ligand on the surface have potential for passive and active targeted delivery of ODN drugs to cancer cells.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004492:Edetic Acid / Q000737:chemistry; D004573:Electrolytes / Q000737:chemistry*; D005434:Flow Cytometry; D005492:Folic Acid / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008823:Micelles; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D004573:Electrolytes; D008024:Ligands; D008823:Micelles; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D005492:Folic Acid; D004492:Edetic Acid