(169a) Engineering Modular Delivery Vehicles Using Biomimetic Polyelectrolytes
Electrostatically driven polymer self-assembly mechanisms are vastly underexplored compared to that of amphiphilic based assemblies, and yet offer unique opportunities for both encapsulation of charged therapeutics and controlled delivery via the tailoring of intermolecular interactions using pH and salt. Additionally, using polypeptide-based materials we have recently shown that oppositely charged polyelectrolytes self-assemble into either liquid or solid complexes because of their secondary structure, providing another avenue to tune material properties. Using molecular engineering, nanoscale stabilization of polyelectrolyte complex formation can be achieved by coupling the polyelectrolyte to a neutral yet hydrophilic block, forming nanometer sized micelles with a polyelectrolyte complex core of either solid or liquid nature and a hydrophilic corona. In this work, we characterize the structure and stability of these polypeptide based model micellar systems using static and dynamic light scattering, electron microscopy, circular dichroism and small angle x-ray scattering. Additionally, we create polyelectrolyte complex micelles that contain therapeutically relevant charged molecules such as miRNA and peptides, specifically for the treatment of atherosclerotic lesions and cancer. The modular nature of these assemblies enables the addition of a targeting ligand to increase the efficacy of delivering miRNA, creating polyelectrolyte complex micelles with a targeting ligand outside the corona of the micelle. Initial cell studies conducted with the different miRNA containing micelles will be discussed.
This work is supported by the University of Chicago and the U.S. Department of Energy Office of Science program in Basic Energy Sciences and the Materials Sciences and Engineering Division.