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Issue 33, 2017
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Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA transfection in dendritic cells

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Abstract

Cationic lipid/co-lipid combinations have been extensively explored in gene delivery as alternatives to viral vectors. To be established as a gold standard of chemical vectors, considerable improvement in their transfection efficiency is however required. Herein, we report a simple procedure to synthesize new cationic lipids and co-lipids for the DNA transfection of dendritic cells (DCs). Seven α-amino-lipophosphonates featuring two aza-heterocycles with protonable sites (imidazole or pyridine) were synthesized and used as co-lipids in liposomes with cationic lipids. For each liposome, the cationic lipid is either an imidazolium lipophosphoramidate (lipid 2) or an α-amino-lipophosphonate containing a basic tertiary aliphatic amine in the polar head group (lipid 3b). The cationic lipids either with new co-lipids or DOPE formed positively charged nano-sized stable liposomes that effectively interact with plasmid DNA (pDNA) to produce lipoplexes. Membrane fusion studies showed that α-amino-phosphonates featuring an imidazole moiety in the polar head group exhibited higher fusion at pH 5.5 than pH 7.4. This study suggests that the best formulations for the transfection of DCs (based on the % transfected cells and the intensity of EGFP-based fluorescence) are lipid 2 associated with either 3a, 3d or DOPE and cationic lipid 3b formulated with 3a or DOPE as a helper lipid. Furthermore, lipid 3a could be used as an alternative to DOPE as a helper lipid. Overall, these results indicate that novel imidazole containing α-amino-phosphonates can serve as effective transfection agents for DC-based vaccines.

Graphical abstract: Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA transfection in dendritic cells

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Publication details

The article was received on 20 Apr 2017, accepted on 15 Jun 2017 and first published on 15 Jun 2017


Article type: Paper
DOI: 10.1039/C7TB01080J
Citation: J. Mater. Chem. B, 2017,5, 6869-6881
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    Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA transfection in dendritic cells

    M. Berchel, S. Akhter, W. Berthe, C. Gonçalves, M. Dubuisson, C. Pichon, P. Jaffrès and P. Midoux, J. Mater. Chem. B, 2017, 5, 6869
    DOI: 10.1039/C7TB01080J

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