Cationic amphiphiles or cationic polymers are used to compact, protect and carry nucleic acids. A fine-tuning of the physicochemical properties of the carrier must be achieved to produce lipoplexes or polyplexes that feature a compromise of stability (ideally, the nanoparticules must be stable outside the cell but not too stable after cell internalization via endocytosis). In particular, the endosome escape is a key point during the transfection process. In our group, we have designed synthetic phospholipids that feature a versatile synthesis [1] and with the possibility to tune the structure of the polar head group [2] and the hydrophobic chains [3]. We and others demonstrated that the use of stearyl lipid chain (C18:0) produce inefficient cationic carriers whereas oleyl chains usually produced efficient carriers.[4] This structural difference can be accounted to a less tight packing of the lipid chains within the supramolecular assemblies; the unsaturation can be view as a disorder element that increases the fluidity. In others studies, we also reported that the use of branched lipid chain (natural [5] or specially designed [6]) also favor the transfection process via an increase of the fluidity or by producing non-lamellar supramolecular assemblies. We explored recently the use of an alternative strategy that consist to incorporate thioether function within the structure of lipid chains.[7] All these strategies offer new possibilities to tune the formulations used for nucleic acid delivery.

New synthetic lipid chains incorporated in the structure of cationic amphiphiles for nucleic acid delivery

2019 Fall National Meeting

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