430746 Tunable Biopolyelectrolyte Complexes As Modular Delivery Vehicles

Monday, November 9, 2015: 9:34 AM
251A (Salt Palace Convention Center)
Lorraine F. Leon and Matthew V. Tirrell, Institute for Molecular Engineering, University of Chicago, Chicago, IL

Electrostatically driven polymer self-assembly mechanisms, such as polyelectrolyte complexation, are vastly underexplored compared to amphiphilic-based assemblies, and yet offer unique opportunities for both the encapsulation of charged therapeutics and controlled delivery via the tailoring of intermolecular interactions using pH and salt.  Moreover, using peptide based materials we can manipulate both electrostatic and hydrogen bonding interactions simultaneously to control the phase behavior of the resultant polyelectrolyte complex.  This allows us to impart tunable material properties that can be exploited for the design of delivery vehicles.  Here we illustrate how hydrogen-bonding interactions can be tuned by utilizing the chirality of the oppositely charged polypeptides leading to manipulation between solid and liquid complexes and support these results both experimentally and with molecular dynamics simulations. 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 scattering techniques, electron microscopy, and circular dichroism.  Additionally, we create bulk and nanophase polyelectrolyte complexes that contain therapeutically relevant charged molecules, such as nucleic acids, and demonstrate that the choice of nucleic acid can also influence phase behavior.  Additionally, the modular nature of these assemblies enables the addition of a targeting ligand to increase the efficacy of delivering nucleic acids, creating polyelectrolyte complex micelles with a targeting ligand outside the corona of the micelle.  Ultimately, we demonstrate the use of targeted polyelectrolyte complex micelles formed using therapeutic nucleic acids that inhibit microRNAs involved in atherogenesis, with the goal of creating a treatment for atherosclerosis.

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See more of this Session: Biomaterials III: Faculty Candidates
See more of this Group/Topical: Materials Engineering and Sciences Division