In vivo tumor targeting of ODN-PEG-folic acid/PEI polyelectrolyte complex micelles.
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.
Jeong
Ji Hoon
JH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Kim
Sun Hwa
SH
Kim
Sung Wan
SW
Park
Tae Gwan
TG
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
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