pH-Responsive Morphological Transitions of Azobenzene-Phospholipid Vesicles.

Abstract

pH-responsive vesicles are promising candidates for passive cancer targeting. These vesicles were constructed from two push-pull azobenzene-containing phospholipids with different substituents, one of which incorporates a pH-sensitive piperazine linker. The amphiphilic molecules self-assemble into spherical bilayer vesicles via π-π stacking, with their morphologies governed by the orientational order of the azobenzene moieties. Mixing the two components facilitates spherical vesicle formation by introducing orientational defects that promote curvature. Under mildly acidic conditions (pH ∼6), protonation of the piperazine group enhances the hydrophilicity of the responsive component, leading to its depletion from the membrane and a consequent shift in composition. This compositional change induces a morphological transition toward a planar bilayer, thermodynamically stabilized by the increased orientational order of the remaining azobenzene units. Such a distinct shape change in response to slight pH variation highlights the potential of these vesicles as smart drug delivery carriers.