Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription.
Lipid envelope-type nanoparticles are promising carriers for gene delivery. The modification of liposomes with polyethyleneglycol (PEG) can often be useful in liposomal formation and pharmacokinetics. However, there is a dilemma concerning the use of PEG because of its poor intracellular trafficking properties. To overcome this problem, in the present study, we report on a strategy for improving the intracellular trafficking of PEG-modified lipid particles by incorporating a short PEG lipid. The findings presented here show that the incorporation of tetra(ethylene)glycol (TEG)-conjugated cholesterol into a liposome composition is useful in controlling the number of lipid envelopes, resulting in an improvement in particle uniformity with a reduced particle size. The TEG-modified lipid particles were found to enhance transfection activity by more than 100-fold. This increase is attributed to an enhancement of cellular uptake, and nuclear transcription by improving intracellular decoating. Moreover, the use of a various short PEG lipids in lipid particle formation showed a clear threshold polymerization degree (less or equal 25: PEG1100), for achieving stimulated transfection activity. Collectively, the use of short PEG lipid promises to be useful in developing an efficient non-viral gene vector.
Masuda
Tomoya
T
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-Ku, Sapporo, Hokkaido 060-0812, Japan.
Akita
Hidetaka
H
Niikura
Kenichi
K
Nishio
Takashi
T
Ukawa
Masami
M
Enoto
Kaoru
K
Danev
Radostin
R
Nagayama
Kuniaki
K
Ijiro
Kuniharu
K
Harashima
Hideyoshi
H
D001120:Arginine / Q000737:chemistry; D001692:Biological Transport; D002467:Cell Nucleus / Q000235:genetics; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes / Q000235:genetics*
D008055:Lipids; D012333:RNA, Messenger; D011092:Polyethylene Glycols; D004247:DNA; D001120:Arginine; D008156:Luciferases