Reengineering Cores and Coronas of Polyelectrolyte Complex Micelles

Electrostatically driven self-assembly mechanisms are vastly underexplored compared to that of amphiphilic based assemblies, and yet offer unique opportunities for encapsulation of charged therapeutics, such as nucleic acids and proteins. Here we focus on electrostatic assemblies called polyelectrolyte complexes, which form by mixing oppositely charged polymers in solution. The resultant complex phase separates into either irregularly shaped solids (or rather glasses), called precipitates, or micron sized liquid droplets that can coalesce into a distinct phase, called a coacervate. This phenomenon can be confined to the nanoscale by using block copolyelectrolytes, which contain a neutral block linked to a charged block, thus forming polyelectrolyte complex micelles with a polyelectrolyte core and neutral polymer corona. This seminar explores molecular engineering strategies to create more stable micelle cores and dynamic thermoresponsive coronas. Core stability is achieved by manipulating the chirality of the polyelectrolyte such that the resulting micellar structure can have both solid and liquid polyelectrolyte cores. Homochiral polypeptide complexes form precipitates with hydrogen bonded b-strand structure. In contrast, if one or more polypeptides is composed of both L and D monomers, coacervates are formed with no secondary structure. The dynamic corona micelles are being developed by using a thermosensitive polymer, poly(N-isopropyl acrylamide) (pNIPAM) as the neutral block. pNIPAM has a lower critical solubility temperature(LCST), above which a hydrophilic to hydrophobic transition occurs. As the corona segments become less soluble, a core-corona inversion could occur that could facilitate the release of molecules in the polyelectrolyte core leading to potential applications in controlled release drug delivery. We are characterizing micelles formed using a diblock copolymer of pNIPAM-b-polyacrylic acid mixed with (1) polylysine and (2) polyethylene glycol-b-polylysine in order to investigate the role of the corona in micelle stability and morphology before and after the temperature transition. Characterization is performed using light, small angle xray scattering, and small angle neutron scattering for the different systems as function of parameters known to influence polyelectrolyte complexes (polymer concentration, charge ratio, pH, salt) and as function of temperature. Through this thorough investigation, we aim to engineer next generation delivery vehicles for nucleic acids, which will be discussed, time permitting.

Biography: Dr. Lorraine Leon is an Assistant Professor in the Materials Science and Engineering Department at the University of Central Florida (UCF). She joined UCF in January 2017 from a postdoctoral appointment at the Institute for Molecular Engineering at the University of Chicago and Argonne National Laboratory. She received her PhD in Chemical Engineering from the Graduate Center of the City University of New York in 2011 where she was awarded a NSFIGERT fellowship and Graduate Teaching Fellowship. Leon obtained her BS in Chemical Engineering and a minor in Mathematics and Chemistry from the University of Florida in 2004. Leon is an experimentalist with research interests at the intersection of biomaterials and polymer science ranging from nanomedicine to the templating of inorganic material. Her lab is focused on expanding the selfassembly toolbox to include multiple, synergistic molecular interactions using biomolecules, particularly peptides and peptide/polymer conjugates.