(635c) Thermosensitive Liposomes With Photo-Activated Small Molecule Release

Forbes, N., University of California, Santa Barbara
Zasadzinski, J. A., University of Minnesota

A drug delivery system with rapid contents release under continuous-wave near-infrared (NIR) light will enable precise spatial and temporal control of drug release.  The drug is encapsulated within a thermosensitive liposome, and rapid drug release is triggered under irradiation by the localized photothermal heating of metallic nanoparticles coupled to the liposome.  These nanoparticles heat the liposome membrane through its phase transition at 39-42°C to induce an increase in membrane permeability.  A fluorescent dye was encapsulated as a model agent to study dye release kinetics.  A small fraction of lysolipid (single-chained phospholipid) enhances the rate of release at the transition.  The lysolipid can partition into pre-formed liposomes to enhance membrane permeability, and this partitioning is impacted by bilayer hydrophilicity and phase.  Two metallic nanoparticles which absorb NIR light, hollow gold nanoshells and copper sulfide nanoparticles, were compared in terms of their liposomal attachment and heating characteristics.  Finally, the anticancer agent doxorubicin was encapsulated within the liposomes and the system was used to deliver doxorubicin to drug-resistant prostate cancer cells (PPC-1) in vitro.  Near-complete cell killing was observed by the photothermally triggered thermosensitive liposomes at an order of magnitude lower doxorubicin concentration relative to non-irradiated liposomal doxorubicin.  The enhanced cell killing at low total concentration is likely due to the rapid release of the doxorubicin, which provides locally higher concentration combined with the thermal damage of the locally increased temperatures. This device provides externally targeted, tumor-specific delivery of small molecule anti-cancer agents from thermosensitive liposomes without requiring bulk tissue hyperthermia, along with expanded control of drug release rate.