Principles and Applications of Functional Lipidic Biomaterials in Molecular Recognition, Membrane Protein Crystallization and Drug Delivery

Abstract

We have designed and synthesized a library of lipids with novel functionalities in order to correlate lipid molecular structure with the ensuing nanomaterial dynamics, stability and phase behavior. The designed lipids were assembled as within lipidic mesophases and their dispersions, forming functional biomaterials that were employed in areas ranging from molecular recognition, sequestration and enrichment of nucleic acids to biosensing. An exciting new class of biomaterials that are based on cyclopropanated lipids was developed. These form stable lipidic cubic phases (LCPs) at low temperature, opening the way to conduct biophysical and biochemical investigations on temperature sensitive bio-macromolecules, specifically membrane proteins. Furthermore, pH-sensitive lipidic matrices for hydrophilic as well as hydrophobic drug incorporation and release were designed, as well as stimuli-responsive lipids that can be incorporated into biomaterials. Efficient pH- and light-induced binding, release and sequestration of hydrophilic dyes were demonstrated. Significantly, these processes could be activated sequentially, thereby achieving high degree of temporal and dosage control. The scope of lipidic materials for drug delivery was expanded to azobenzene-containing hexagonal phases, in which “on demand” single-step as well as sequential light-triggered release and retention of embedded dye molecules were demonstrated. Finally, cubosomes were stabilized and functionalized with a novel, designed biotin-based block copolymer, resulting in dispersed biomaterials that were applied against the human adenocarcinoma cell line HeLa. These cubosomes are able to simultaneously transport paclitaxel, a potent anti-cancer drug, and a hydrophobic fluorescent dye in active targeting of cancer cells. Such biotinylated cubosomes are potentially applicable in diagnosis, drug delivery and monitoring of therapeutic response for active targeting versus cancer cells.