Cell membrane fusing liposomes for cytoplasmic delivery in brain endothelial cells.

Cell membrane fusing liposomes for cytoplasmic delivery in brain endothelial cells. Colloids Surf B Biointerfaces. 2020 Jun 24;194:111193 Authors: Farid M, Faber T, Dietrich D, Lamprecht A Abstract Direct cytoplasmic delivery is essential for susceptible molecules as proteins and some nucleic acids to improve their therapeutic efficacy in cells. Using liposomes for their delivery proved challenging due to known uptake by endocytosis followed by partial or complete lysosomal breakdown. Thus, "fusogenic" liposomes (FL) composed of the neutral lipid dioleoylphosphatidylethanolamine (DOPE) combined with the cationic lipid 1, 2-dioleoyl-3-trimethylammoniumpropane (DOTAP) were tested in different ratios for their cell membrane fusion ability and their cytoplasmic delivery was compared to "pH-sensitive" liposomes in murine brain endothelial cells (bEnd.3). They were loaded with cargos of different molecular sizes (calcein/ enhanced green fluorescent-protein (EGFP)/ EGFP coding plasmid) and their intracellular delivery was quantitatively and qualitatively analyzed. FL composed of equimolar ratios of DOPE and DOTAP showed the most efficient cytoplasmic delivery of all cargos by fusing with the cell membranes within the first 15 min of addition. Their EGFP plasmid delivery to cells was quantified to be 58.2 ± 9.5 % of the total EGFP load and calcein delivery was measured in buffer to be 64.1 ± 4.0 % of the total calcein load, and r...
Source: Colloids and Surfaces - Category: Biotechnology Authors: Tags: Colloids Surf B Biointerfaces Source Type: research