Structure-property relationships for polyelectrolyte complexation with nucleic acids

Polyelectrolyte complexes (PECs) are formed through the association of oppositely charged polymers, phase separated in solution. If at least one polyelectrolyte is conjugated to a neutral polymer, phase separation occurs at the nanoscale, resulting in polyelectrolyte complex micelles (PCMs). PCMs have shown promise for delivery of charged therapeutics, but the structural impact of using biomacromolecules in assembly is still limited. In this talk, I will discuss on our work to understand the assembly and behavior of PECs and PCMs that contain nucleic acids as the anionic polyelectrolyte. In this situation, helix formation and charged backbone chemistry can drastically influence assembly, material properties, morphology, and stability. Our investigations span the impact of physical and chemical properties of each polyelectrolyte using small angle X-ray scattering, dynamic light scattering, and electron microscopy. This covers the impact of nucleic acid sequence, ion atmosphere, backbone modifications, polymer chemistry, and more. These observations narrow the design space for tailored therapeutic micelles and provide new insights into the physics of polyelectrolyte self-assembly.