(59k) Evaluating Physical Properties and Stability of Nucleic Acid Polyelectrolyte Micelles

Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a hydrophilic charged-neutral block copolymer) offer a solution to the critical problem of delivering therapeutic nucleic acids. Still, few systematic studies have been conducted on how parameters such as polymer charge density, hydrophobicity, and choice of charged group influence PCM properties, despite evidence that these strongly influence the complexation behavior of polyelectrolyte homopolymers. Using small angle X-ray scattering and electron microscopy we investigate the relationship between the physical properties of oligonucleotide PCMs and chemical properties of the nucleic acids and block copolymers that form them. For instance, differences in charge density and hydrophobicity have been individually suggested to provide increased complex stability, but we find that other factors may disrupt this trend. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the polymer physics of polyelectrolyte self-assembly.