Dithiane-based photolabile amphiphiles: Toward photolabile liposomes

A series of externally and internally sensitized photolabile amphiphiles having their hydrophilic headgroups and hydrophobic tails tethered via the dithiane-based photocleavable "latch" is prepared. These lipids are tested in various formulations with naturally occurring phospholipids and/or cholesterol to prepare light-sensitive liposomes. Irradiation of such liposomes in phosphate-buffered saline solution (medium-pressure mercury lamp, Pyrex filter, lambda > 300 nm) increases the bilayer permeability and accelerates the release of entrapped small organic molecules by up to an order of magnitude. A novel assay, based on H-1 or F-19 pulsed field gradient NMR measurements of diffusion coefficients, is developed to monitor the lifetimes of dark leakage and light-induced unloading of the probe molecules.