Laser-Triggered Release of Entrapped Photo-Reactive Solutes from Liposomes Containing Diacetylenic Phosphatidylcholine

We have previously reported on a novel class of light-triggerable liposomes prepared from a photopolymerizable phospholipid DC8,9PC (1,2- bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) and DPPC (1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine)1,2. UV radiation (254 nm) exposure on the liposomes resulted in photopolymerization of DC8,9PC which subsequently resulted in the release of contents (see abstract at this meeting by Puri et al). Treatment of these liposomes by 514 nm laser light is also found to promote the release of encapsulated calcein (Ex/Em 490/517 nm) or (an anticancer drug) Doxorubicin (Ex/Em 490/590 nm); however the onset of this release is dramatically rapid and is found to occur within 1-2 minutes of laser treatment in contrast to greater than 10 minutes after the 254 nm UV exposure. When a different dye: calcein-blue (Ex/Em 360/460 nm) was encapsulated in the liposomes, the 514 nm laser exposure treatments did not release the calcein-blue dye suggesting the release mechanism to be wavelength specific. The 514 nm laser treatment on calcein loaded liposomes did not result in any measurable chemical changes in the lipids as determined by LC-MS and morphological changes in the liposomes as determined by Cryo electron microscopy. The 514 nm treatment of calcein-loaded liposomes also resulted in the production of reactive oxygen species as determined through ROS assays. Moreover, the laser-induced release of calcein was inhibited in the presence of oxygen radical scavengers. Based on these observations, we propose that visible-light triggered release of entrapped solutes from DPPC/DC8,9PC liposomes occurs via a novel mechanism that involves photo-sensitizer-generated reactive oxygen species to perturb DC8,9PC in the liposome membrane. These formulations are currently under investigations for drug delivery/release applications.