Functionalized Phospholipid Molecular Platform: Use for Production of Cationic Fluorescent Lipids

Berchel, Mathieu; Haelters, Jean‐Pierre; Afonso, Damien; Maroto, Alicia; Deschamps, Laure; Giamarchi, Philippe; Jaffrès, Paul‐Alain

doi:10.1002/ejoc.201301416

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Accordingly, the synthesis of amphiphilic compounds possessing a trialkyl phosphate group as a tether between the lipid domain and the cationic polar head must be achieved according to another synthetic scheme. In recent works, we have reported a new methodology for the synthesis of cationic phosphoramidates that possess either two different lipid chains19 or one fluorescent lipid chain 20. This methodology uses POCl 3 as a starting material.…”

Section: Resultsmentioning

confidence: 99%

Cationic Trialkylphosphates: Synthesis and Transfection Efficacies Compared to Phosphoramidate Analogues

et al. 2014

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International audienceWe report herein the synthesis of a novel family of cationic lipids, characterized by a trimethylammonium headgroup linked through a phosphate function to either two identical or two different lipid chains. The novelty of this study arises from the use of a trialkyl phosphate group to associate the hydrophobic domain to the cationic polar head. The structure of these new cationic lipids, which differs from that of previously reported lipophosphoramidates, is closer to the phospholipids encountered in the plasma membrane, and possesses a phosphocholine polar head. Evaluation of the transfection activity allowed us to compare the efficacy of cationic lipophosphates with that of lipophosphoramidates. These results demonstrate that cationic lipophosphates and lipophosphoramidates having otherwise identical chemical structures exhibit similar transfection efficacies. The second conclusion is that the structure of the lipid domain is a much more important parameter in governing transfection efficacy than the composition of the linker moiety. The best results were obtained with cationic lipophosphates or lipophosphoramidates possessing two different lipid chains, for example one oleyl chain with one phytanyl chain. These nonsymmetric cationic lipids exhibited transfection efficacies that were 10- to 200-fold better than those obtained with Lipofectamine used as a commercial standard

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Section: Resultsmentioning

confidence: 99%

Cationic Trialkylphosphates: Synthesis and Transfection Efficacies Compared to Phosphoramidate Analogues

et al. 2014

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“…This work demonstrated also the duality of the pegylation, providing a high bioavailability, but limiting transfection capacity. Such multimodular synthetic systems could be used to guide the formulation of complexes and some new fluorescent compounds will be explored in the near future [ 35 ] using FRET (Förster Resonance Energy Transfer) activity.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, different cationic lipids such as lipophosphonates [ 15 , 16 , 17 ] and lipophosphoramidates [ 12 , 13 , 18 , 19 , 20 , 21 ] have been produced, and their high ability to transfect cells in culture and lungs mice were demonstrated [ 13 , 22 , 23 , 24 , 25 , 26 , 27 ]. However, the plasmid type [ 27 , 28 , 29 ], the vector [ 18 , 26 , 29 , 30 , 31 , 32 ] as well as the nucleic acids (NA) or synthetic carrier’s labeling techniques [ 8 , 30 , 33 , 34 , 35 ], impact greatly the distribution in tissues as well as the transgene expression. Labeling liposomes with a fluorescent probe appears as a relevant procedure to establish biodistribution profiles of lipoplexes and their pharmacokinetics, irrespective of administration route [ 26 , 27 , 31 , 32 , 33 , 34 , 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of New Fluorescent Lipophosphoramidates for Gene Transfer and Biodistribution Studies after Systemic Administration

Belmadi

Berchel

Denis

et al. 2015

IJMS

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The objective of lung gene therapy is to reach the respiratory epithelial cells in order to deliver a functional nucleic acid sequence. To improve the synthetic carrier’s efficacy, knowledge of their biodistribution and elimination pathways, as well as cellular barriers faced, depending on the administration route, is necessary. Indeed, the in vivo fate guides the adaptation of their chemical structure and formulation to increase their transfection capacity while maintaining their tolerance. With this goal, lipidic fluorescent probes were synthesized and formulated with cationic lipophosphoramidate KLN47 (KLN: Karine Le Ny). We found that such formulations present constant compaction properties and similar transfection results without inducing additional cytotoxicity. Next, biodistribution profiles of pegylated and unpegylated lipoplexes were compared after systemic injection in mice. Pegylation of complexes led to a prolonged circulation in the bloodstream, whereas their in vivo bioluminescent expression profiles were similar. Moreover, systemic administration of pegylated lipoplexes resulted in a transient liver toxicity. These results indicate that these new fluorescent compounds could be added into lipoplexes in small amounts without perturbing the transfection capacities of the formulations. Such additional properties allow exploration of the in vivo biodistribution profiles of synthetic carriers as well as the expression intensity of the reporter gene.

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“…The transport process can be categorized into five steps: the extra-cellular gene delivery, cellular uptake, endosomal escape, nuclear translocation, and transcription/translation (Figure 3) [14]. Therefore, the molecular platforms have allowed producing cationic lipids with additional properties, such as fluorescence, stealth, targeting, etc., without affecting the amphiphilic nature of the lipids [38]. And because of these advancements, the organic fluorescent lipids have achieved advantages, such as simplicity of synthesis, biodegradability, cellular monitoring, and good repeatability, over other vectors [37].…”

Section: Functional Fluorescent and Non-fluorescent Vectorsmentioning

confidence: 99%

The Development of Functional Non-Viral Vectors for Gene Delivery

Patil

Gao

Lin

et al. 2019

IJMS

194

135

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Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

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Functionalized Phospholipid Molecular Platform: Use for Production of Cationic Fluorescent Lipids

Cited by 10 publications

References 40 publications

Cationic Trialkylphosphates: Synthesis and Transfection Efficacies Compared to Phosphoramidate Analogues

Cationic Trialkylphosphates: Synthesis and Transfection Efficacies Compared to Phosphoramidate Analogues

Evaluation of New Fluorescent Lipophosphoramidates for Gene Transfer and Biodistribution Studies after Systemic Administration

The Development of Functional Non-Viral Vectors for Gene Delivery

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