(410d) Structure-Property Relationships of Polyelectrolyte Complex Micelles for Nucleic Acid Delivery

Developing effective non-viral methods for delivery of nucleic acids and other macromolecular therapeutics is one of the most pressing challenges in nanomedicine. The immense potential of engineered nucleic acids as therapeutic agents is limited by the difficulty of overcoming physical and biological barriers. A solution to this critical problem is using hydrophilic charged block polymers to condense nucleic acids, driving nanoscale phase separation to form polyelectrolyte complex micelles (PCMs). These core-shell nanoparticles sequester and protect nucleic acids from nucleases and immune response. Still, few systematic studies have been conducted on how parameters such as nucleic acid backbone chemistry, polymer charge density and polymer length influence PCM properties, despite evidence that these strongly influence complexation behavior. Here, I will discuss our investigations of the impact of physical and chemical properties of each polyelectrolyte on complex assembly using small angle X-ray scattering, dynamic light scattering, and electron microscopy. We found the physical size and molecular structure of the nucleic acid backbone and cationic charged group strongly influence complexation behavior and stability and have determined scaling behaviors for micelle size and aggregation number. These observations narrow the design space for tailored therapeutic micelles and provide new insights into the physics of polyelectrolyte self-assembly.