mRNA Lipoplexes with Cationic and Ionizable α-Amino-lipophosphonates: Membrane Fusion, Transfection, mRNA Translation and Conformation

International audienceCationic liposomes are attractive carriers for mRNA delivery. Here, mRNA lipoplexes (LX) were prepared with the cationic lipids α-aminolipophosphonate (3b) or imidazolium lipophosphoramidate (2) associated with various α-aminolipophosphonates co-lipids comprising protonable groups (imidazole or pyridine) and DOPE. Physicochemical parameters of liposomes and their membrane fusion activity were measured. LXs comprising either 3b- or 2- allowed transfection of ~25% and 40% of dendritic cells with low cytotoxicity, respectively; the efficiency increased up to 80% when 2 was combined with the imidazole-based co-lipid 1. The transfections were high with 3b/1, 3b/DOPE, 2/1 and 2/DOPE LXs. We observed that the transfection level was not well correlated with the acid-mediated membrane fusion activity of liposomes supposed to destabilize endosomes. The mRNA release from LXs and its translation capacity after release were studied for the most efficient LXs. The results showed that the more mRNA was condensed, the poorer the translation efficiency after release was. In contrast to DNA, circular dichroism performed on mRNA complexed with 2/DOPE revealed the presence of denatured mRNA in LXs explaining this lack of translation efficiency. This is an important parameter that should be stressed for the preparation of mRNA LXs with a conserved mRNA translation activity

Evaluation of lipophosphoramidates-based amphiphilic compounds on the formation of biofilms of marine bacteria

International audienceThe bacteriostatic and/or bactericidal properties of few phosphoramide-based amphiphilic compounds on human pathogenic bacteria were previously reported. In this study, the potential of two cationic (BSV36 and KLN47) and two zwitterionic (3 and 4) amphiphiles as inhibitors of marine bacterial growth and biofilm formation were investigated. Results showed that the four compounds have little impact on the growth of a panel of 18 selected marine bacteria at a concentration of 200 µM, and up to 700 µM for some bacterial strains. Interestingly, cationic lipid BSV36 and zwitterionic lipids 3 and 4 effectively disrupt biofilm formation of Paracoccus sp. 4M6 and Vibrio sp. D02 at 200 µM and to a lesser extent of seven other bacterial strains tested. Moreover, ecotoxicological assays on four species of microalgae highlighted that compounds 3 and 4 have little impact on microalgae growth with EC50 values of 51 µM for the more sensitive species and up to 200 µM for most of the others. Amphiphilic compounds, especially zwitterionic amphiphiles 3 and 4 seem to be promising candidates against biofilm formation by marine bacteria

Phosphonodithioformate-amine coupling reaction: from basic discovery to application for the functionalization of liposomes

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Evaluation of the transfection efficacies of quaternary ammonium salts prepared from sophorolipids

Five quaternary ammonium amphiphilic compounds were synthesized from sophorolipid 1. These compounds were formulated in aqueous media and some of them (5 and 6) produced well-defined supramolecular aggregates which were characterized by DLS and zeta measurements. Their capacity to transfect four different eukaryotic cell lines in vitro was assessed. To evaluate the influence of the carbohydrate head group from the sophorolipids on the transfection efficacies, their deglycosylated analogues were also synthesized and tested for gene delivery. For all the compounds, the use of DOPE as a helper lipid in a 1 : 1 molar ratio with the ammonium-based lipids was required to obtain homogeneous formulations. The transfection results indicate that quaternary ammonium-based sophorolipids proved to be more efficient pDNA carriers than their deglycosylated counterparts. Moreover, the presence of the carbohydrate head group clearly contributed to the good biocompatibility of these cationic lipids. These cationic sophorolipid derivatives thus offer good potential for the development of new vectors for gene delivery based on renewable resources

CCDC 638483: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures