Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription

• Published in: Biomaterials Vol. 30; no. 27; pp. 4806 - 4814
• Main Authors: Masuda, Tomoya, Akita, Hidetaka, Niikura, Kenichi, Nishio, Takashi, Ukawa, Masami, Enoto, Kaoru, Danev, Radostin, Nagayama, Kuniaki, Ijiro, Kuniharu, Harashima, Hideyoshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-09-2009
• Subjects: Advanced Basic Science; Arginine - chemistry; Biological Transport; Cell Nucleus - genetics; Dentistry; DNA - metabolism; Envelope-type lipid nanoparticle; Gene delivery; HeLa Cells; Humans; Intracellular Space - metabolism; Intracellular trafficking; Lipids - chemistry; Luciferases - genetics; Luciferases - metabolism; Microscopy, Confocal; Molecular Weight; Nanoparticles - chemistry; Non-viral vector; Plasmids - metabolism; Polyethylene Glycols - chemistry; Protein Biosynthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Short PEG; Transcription, Genetic; Transfection; Transgenes - genetics; Gene delivery; Non-viral vector; Envelope-type lipid nanoparticle; Short PEG; Intracellular trafficking
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.05.036

Abstract 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.