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Selective gene delivery in dendritic cells with mannosylated and histidylated lipopolyplexes.
- Source :
-
Journal of drug targeting [J Drug Target] 2011 Jun; Vol. 19 (5), pp. 315-25. Date of Electronic Publication: 2010 Jul 23. - Publication Year :
- 2011
-
Abstract
- We report for the first time preparation of mannosylated and histidylated lipopolyplexes (Man-LPD100) with uptake and transfection selectivity for dendritic cells (DCs). Man-LPD100 were prepared by addition of mannosylated and histidylated liposomes (Man-Lip100) on preformed PEGylated histidylated polylysine/DNA polyplexes. Man-Lip100 comprised a cationic [O,O-dioleyl-N-(3N-(N-methylimidazolium iodide)propylene) phosphoramidate)] lipid, a neutral [O,O-dioleyl-N-histamine Phosphoramidate] co-lipid and β-D-mannopyranosyl-N-dodecylhexadecanamide (Man-lipid). At the best, Man-Lip100 containing 11 mol % Man-lipid was obtained. We found that dialysis of liposomes completely abolished cytotoxicity. We showed that the uptake of Man(11)-LPD100 by the murine DC line (DC2.4 cells) was at least 10-fold higher than that of Lac(6)-LPD100. A confocal microscopy study with DC2.4 cells expressing Rab5-EGFP or Rab7-EGFP, revealed that DNA uptake occurred through clathrin-mediated endocytosis. The transfection of DC2.4 cells with Man(11)-LPD100 containing DNA encoding luciferase gene gave luciferase activity two to three times higher (9 × 10(5) RLU/mg protein) than with non-mannosylated LPD100. In contrast to the latter, it was inhibited by 90% in the presence of mannose. Overall, the results indicate that mannosylated and histidylated LPD is a promising system for a selective DNA delivery in DCs.
- Subjects :
- Animals
Cell Culture Techniques
Cell Line
Cell Survival drug effects
DNA genetics
Drug Carriers toxicity
Drug Compounding
Endocytosis
Endosomes metabolism
Green Fluorescent Proteins genetics
Liposomes
Luciferases, Firefly genetics
Luciferases, Firefly metabolism
Mice
Microscopy, Confocal
Particle Size
Plasmids
Transfection
rab GTP-Binding Proteins genetics
rab5 GTP-Binding Proteins genetics
rab7 GTP-Binding Proteins
DNA administration & dosage
Dendritic Cells metabolism
Drug Carriers chemistry
Gene Transfer Techniques
Histidine chemistry
Mannose chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2330
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of drug targeting
- Publication Type :
- Academic Journal
- Accession number :
- 20653408
- Full Text :
- https://doi.org/10.3109/1061186X.2010.504262