We use model lipid membranes in the form of vesicles to study pH-controlled lateral lipid phase separation with the goal to direct the vesicles' surface topography and functionality, the vesicles' membrane permeability and fusogenicity. Integration of these processes on nanometer-sized lipid vesicles used as drug delivery carriers may precisely control their interactions with diseased cells increasing therapeutic efficacy while minimizing toxicities.
Two examples of improving the therapeutic potential in liposomal chemotherapy and alpha-particle radiotherapy will be presented: first, the description and demonstration of the efficacy of vesicles with 'sticky patches'. These vesicles introduce new binding geometries with isolated cell surface receptors, and enable selective targeting and effective killing of cancer cells currently reported as untargetable by today's reported nanoparticles; and second, the description of highly diffusing forms of lethal agents delivered and released within the tumor interstitium, and the demonstration of using this approach to effectively address the limited drug penetration and heterogeneous drug distributions in solid tumors that currently limit the therapeutic efficacy of these agents.