(44b) Polyelectrolyte Complex Micelles As Vehicles for miRNA Delivery

Electrostatically driven micellization is a useful way of assembling functional nanostructures because of the ability to tune intermolecular interactions using pH and salt.  Studies have shown that the macroscopic phenomenon of complex coacervation can be achieved at the nanoscale by coupling the polyelectrolyte to a neutral yet hydrophilic block, forming micelles with a coacervate core and a hydrophilic corona.   Polypeptides have been used as a model system to study both complex coacervates and coacervate core micelles.  Interestingly, the ability of polypeptides to participate in secondary structure formation impedes complex coacervation and affects the structure of the corresponding polyelectrolyte complex micelles.  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.  To increase the efficacy of delivering miRNA, we use triblock copolymers consisting of a polyelectrolyte block, a polyethylene oxide block, and a targeting ligand, 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.