A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG hybrid conjugate micelles.
The conjugate of antisense c-raf oligonucleotide (ODN) and poly(ethylene glycol) (PEG) was synthesized for intracellular ODN delivery. When combined with polyethylenimine (PEI), the ODN-PEG conjugate self-associated to form polyelectrolyte complex micelles in aqueous solution. The effective hydrodynamic diameter of the micelles was ca. 70 nm with a narrow size distribution. Flow cytometry analysis indicated that the cellular uptake of the micelles by A2780 cells was much higher than that of ODN alone. The micelles also showed a superior antiproliferative activity against ovarian cancer cells in vitro and in vivo.
Jeong
Ji Hoon
JH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Kim
Sung Wan
SW
Park
Tae Gwan
TG
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004573:Electrolytes / Q000737:chemistry; D006801:Humans; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D009368:Neoplasm Transplantation / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012996:Solutions; D013997:Time Factors
D004337:Drug Carriers; D004573:Electrolytes; D008823:Micelles; D016376:Oligonucleotides, Antisense; D012996:Solutions; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D019908:Proto-Oncogene Proteins c-raf