7 results on '"Jaffrès PA"'
Search Results
2. Cationic lipophosphoramidates containing a hydroxylated polar headgroup for improving gene delivery.
- Author
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Berchel M, Le Gall T, Haelters JP, Lehn P, Montier T, and Jaffrès PA
- Subjects
- Gene Transfer Techniques, Hydroxylation, Liposomes chemistry, Quaternary Ammonium Compounds chemistry, Cations chemistry, Drug Carriers chemistry, Lipids chemistry
- Abstract
The structure of the cationic moiety of amphiphiles is a key factor which directly influences their transfection efficacy. Accordingly, in the present work, we have synthesized three new lipophosphoramide-based amphiphilic compounds incorporating a methoxy 5, hydroxyl 6, or dihydroxyl 7 functional group in their cationic part. Gene delivery efficacies of these novel vectors were compared to our benchmark compound, the arsenolipophosphoramidate KLN47, and to its trimethylammonium (TMA) analogue 4. We next studied the characteristics (size, ζ potential) of the nanometric assemblies formed (liposomes and lipid/DNA complexes), and the DNA binding ability of the cationic liposomes was characterized at the physicochemical level. In vitro, all of the cationic lipids evaluated were efficient not only to condense plasmids but also to transfect two types of human airway epithelial cells. Interestingly, in vivo administration to mice (via simple tail vein injection) showed that compound 6 was the most efficient in transfecting the lungs when compared to that of the other cationic lipids studied, including compound KLN47. All of these results suggest that a hydroxyethyldimethylammonium (HE-DMA) polar head could be a valuable alternative to a trimethylarsonium (TMAs) polar head and that they also invite further evaluation of the in vivo potential of compound 6 using more clinically relevant delivery procedures.
- Published
- 2015
- Full Text
- View/download PDF
3. Cationic dialkylarylphosphates: a new family of bio-inspired cationic lipids for gene delivery.
- Author
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Le Corre SS, Belmadi N, Berchel M, Le Gall T, Haelters JP, Lehn P, Montier T, and Jaffrès PA
- Subjects
- Biomimetic Materials chemical synthesis, Biomimetic Materials toxicity, Cell Line, DNA chemistry, DNA genetics, Drug Carriers chemical synthesis, Drug Carriers toxicity, Humans, Hydrophobic and Hydrophilic Interactions, Lipids chemical synthesis, Lipids toxicity, Liposomes, Biomimetic Materials chemistry, Drug Carriers chemistry, Lipids chemistry, Phosphates chemistry, Transfection methods
- Abstract
In this work that aims to synthesize and evaluate new cationic lipids as vectors for gene delivery, we report the synthesis of a series of cationic lipids in which a phosphate functional group acts as a linker to assemble on a molecular scale, two lipid chains and one cationic polar head. The mono or dicationic moiety is connected to the phosphate group by an aryl spacer. In this work, two synthesis strategies were evaluated. The first used the Atherton-Todd coupling reaction to introduce a phenolic derivative to dioleylphosphite. The second strategy used a sequential addition of lipid alcohol and a phenolic derivative on POCl3. The two methods are efficient, but the latter allows larger yields. Different polar head groups were introduced, thus producing amphiphilic compounds possessing either one permanent (N-methyl-imidazolium, pyridinium, trimethylammonium) or two permanent cationic charges. All these cationic lipids were formulated as liposomal solutions and characterized (size and zeta potential). They formed stable liposomal solutions both in water (at pH 7.0) and in a weakly acidic medium (at pH 5.5). Finally, this new generation of cationic lipids was used to deliver DNA into various human-derived epithelial cells cultured in vitro. Compared with Lipofectamine used as a reference commercial lipofection reagent, some cationic dialkylarylphosphates were able to demonstrate potent gene transfer abilities, and noteworthily, monocationic derivatives were much more efficient than dicationic analogues.
- Published
- 2015
- Full Text
- View/download PDF
4. Selective gene delivery in dendritic cells with mannosylated and histidylated lipopolyplexes.
- Author
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Perche F, Gosset D, Mével M, Miramon ML, Yaouanc JJ, Pichon C, Benvegnu T, Jaffrès PA, and Midoux P
- 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
- 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.
- Published
- 2011
- Full Text
- View/download PDF
5. Fluorescence study of lipid-based DNA carriers properties: influence of cationic lipid chemical structure.
- Author
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Burel-Deschamps L, Mével M, Loizeau D, Ayadi F, Yaouanc JJ, Clément JC, Jaffrès PA, and Giamarchi P
- Subjects
- Cations chemistry, Chemistry, Physical, DNA genetics, Fluorescence Polarization, Fluorescence Resonance Energy Transfer, Fluorescent Dyes metabolism, Gene Transfer Techniques, Genetic Vectors, Lipids genetics, Liposomes chemistry, Molecular Structure, Phospholipids chemistry, Phospholipids genetics, Rhodamines metabolism, Spectrometry, Fluorescence, Viscosity, DNA chemistry, Drug Carriers chemistry, Fluorescence, Lipids chemistry
- Abstract
We report here a study on the physicochemical properties of cationic phospholipids liposomes used for lipoplex formulation and DNA transfer. The original cationic phospholipids synthesized in our laboratory are first presented with the liposome formulation process. The second part deals with the liposomes fusogenic properties studied by fluorescence resonant energy transfer (FRET). The nature of the cationic polar head and the formulation with or without a neutral colipid have a great influence on the FRET signal. The third part reports the study of the viscosity of the liposome by fluorescence anisotropy measurements. It has been observed that the vectors having a saturated lipid chain exhibit a more pronounced anisotropy than those having unsaturated lipid chains. Finally, liposomes formed by a mixture of phospholipids and DC-Chol (a rigid lipid) leads to increase the anisotropy denoting a more rigid liposome.
- Published
- 2008
- Full Text
- View/download PDF
6. Lipophosphoramidates as lipidic part of lipospermines for gene delivery.
- Author
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Lamarche F, Mével M, Montier T, Burel-Deschamps L, Giamarchi P, Tripier R, Delépine P, Le Gall T, Cartier D, Lehn P, Jaffrès PA, and Clément JC
- Subjects
- Cations, DNA administration & dosage, DNA genetics, Drug Carriers pharmacology, Fluorescence Resonance Energy Transfer, Models, Chemical, Particle Size, Transfection methods, DNA metabolism, Drug Carriers chemical synthesis, Gene Transfer Techniques, Liposomes chemistry, Nanostructures chemistry, Phosphatidylethanolamines chemistry, Spermine chemistry
- Abstract
The DNA compacting properties of polyamines (especially spermine) are well-known, hence the use of spermine as the cationic part in several synthetic DNA carriers. Here, we describe the synthesis of modified spermines, with a "lipophosphoramidate" as the lipidic part, and their use for efficient in vitro transfection. Physicochemical measurements (particle size, zeta potentials, pKa determination) and gel retardation assays were also performed. Theoretical membrane-disrupting ability was established by FRET. Taken together, our results indicate that lipophosphoramidates constitute an interesting alternative to "classical" lipidic parts of cationic lipids used as DNA carriers.
- Published
- 2007
- Full Text
- View/download PDF
7. Dicationic lipophosphoramidates as DNA carriers.
- Author
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Mével M, Montier T, Lamarche F, Delépine P, Le Gall T, Yaouanc JJ, Jaffrès PA, Cartier D, Lehn P, and Clément JC
- Subjects
- Animals, Cations, Cell Line, Tumor, Cytotoxicity Tests, Immunologic, DNA administration & dosage, DNA genetics, HeLa Cells, Humans, Luminescent Measurements, Phosphoramides, Time Factors, Amides chemical synthesis, DNA metabolism, Drug Carriers chemical synthesis, Gene Transfer Techniques, Phospholipids chemical synthesis, Phosphoric Acids chemical synthesis
- Abstract
Lipophosphoramidates with two different permanent cations as polar heads were synthesized and evaluated for their gene transfer activity. Physicochemical measurements (particle size, zeta potentials) and gel retardation assays were also performed. In vitro biological evaluation was conducted with A542 and HeLa cell lines, and cytotoxicity determined by a chemiluminescent assay. The set of results indicates that, on the whole, dicationic lipophosphoramidates constitute an interesting alternative to their monocationic analogues.
- Published
- 2007
- Full Text
- View/download PDF
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