Phosphatase‐Triggered Fusogenic Liposomes for Cytoplasmic Delivery of Cell‐Impermeable Compounds

Abstract

License to fuse! A phosphorylated fusion peptide can mediate membrane fusion when the phosphates (green triangles, see scheme) are removed by phosphatases (blue spheres), delivering the contents of the liposome into the cytosol. This phosphatase‐triggered approach may be useful to create target‐specific lipid nanocarriers.

Facile synthesis of partially uncapped liposomes

“…3a). The 40 °C condition might cause the impaired liposomal structures to rapidly recover [1][2][3]. However, the 2 °C condition appeared to accelerate the full fragmentation of the liposomes, which resulted from limited recovery (due to the lipid low rigidity) [1][2][3] of the impaired liposomal structures at the low temperature (Fig.…”

“…2c) due to significant M a n u s c r i p t 1 0 increases in the FUL and IL fractions. The fragmented FULs were expected to rapidly recover their liposomal structures due to the self-assembly characteristics of lipids into vesicular lipid bilayers in water [1][2][3], which increased the IL fraction. Here, we enlarged the TEM images to clearly visualize the shapes of the ILs, OSLs, TSLs, UCLs, and FULs (Fig.…”

“…Lipids with suitable hydrophilic/lipophilic proportions self-assemble in water into vesicular lipid bilayers [1][2][3]. Hydrophilic or lipophilic bioactive species are usually contained in a hydrophilic inner core or a lipid bilayer shell, respectively [1].…”

“…Over the last few decades, liposome-based delivery systems for chemical or biological molecular candidates have received much attention and offer various possibilities in the biomedical and cosmetic fields [1][2][3]. In particular, many research efforts have been focused on developing functional liposomes using chemically/physically modified lipids and antibody-or ligand-anchored lipids for targeted disease therapy and controlled delivery of drug content [1][2][3][4][5]. These studies have even adopted functional amphiphilic polymers to artificially constitute liposome-like vesicular structures [5].…”

“…The dynamic properties of lipid bilayers, including fusion, fission, and shape deformation, are usually affected by various experimental conditions [1][2][3]6,7]. For example, a water-soluble cytoskeletal sub-membranous protein (e.g., talin) can shield the hydrophobic portion at the edge of the lipid bilayer and induce the formation of a transient hole in the liposome that results from the temporary suppression of the growth of the lipid bilayer at the edge [6].…”