Abstract

We describe the preparation and characterization of block liposomes, a new class of liquid (chain-melted) vesicles, from mixtures of the highly charged (+16 e) multivalent cationic lipid MVLBG2 and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). Block liposomes (BLs) consist of distinct spherical, tubular vesicles, and cylindrical micelles that remain connected, forming a single liposome. This is in contrast to typical liposome systems, where distinctly shaped liposomes are macroscopically separated. In a narrow composition range (8-10 mol% MVLBG2), an abundance of micrometer-scale BLs (typically sphere-tube-sphere triblocks) is observed. Cryo-TEM reveals that BLs are also present at the nanometer scale, where the blocks consist of distinctly shaped nanoscale spheres, pears, tubes, or rods. Pear-tube diblock and pear-tube-pear triblock liposomes contain nanotubes with inner lumen diameter 10-50 nm. In addition, sphere-rod diblock liposomes are present, containing rigid micellar nanorods approximately 4 nm in diameter and several microm in length. Block liposomes may find a range of applications in chemical and nucleic acid delivery and as building blocks in the design of templates for hierarchical structures.