Content Delivery of Lipidic Nanovesicles in Electropermeabilized Cells

Lipidic nanovesicles (the so-called liposomes) were among the one of the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. In most models, it appears to be linked to endocytotic transfer. Their direct content delivery can be enhanced by electric field pulses applied to a cell liposomes mixture. The optimal form for liposomes was shown to be large unilamellar vesicles (LUV). The present communication describes an optimization to enhance the delivery. When lipidic nanovesicles (LUVs) are electrostatically brought in contact with electropermeabilized cells by a salt bridge, their content is delivered into the cytoplasm of electropermeabilized cells. The PEF parameters are selected to affect specifically the cells leaving the vesicles unaffected. Cell viability is positively affected by the treatment. High-field short pulses are more efficient than low-field long pulses. A homogeneous cytoplasm labeling is observed under digitized videomicroscopy. The process is a content mixing, not an endocytotic pathway. The lipidic composition of the LUV should contain charged lipids (phosphatidylserine), fusion promoting lipids (phosphatidylethanolamine), and cholesterol.