Date of Award

Spring 5-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Polymers and High Performance Materials

Committee Chair

Daniel Savin

Committee Chair Department

Polymers and High Performance Materials

Committee Member 2

Charles McCormick

Committee Member 2 Department

Polymers and High Performance Materials

Committee Member 3

Sarah Morgan

Committee Member 3 Department

Polymers and High Performance Materials

Committee Member 4

Derek L. Patton

Committee Member 4 Department

Polymers and High Performance Materials

Committee Member 5

Robson Storey

Committee Member 5 Department

Polymers and High Performance Materials

Abstract

This document details work in the area of amphiphilic polypeptide-based block copolymers that are able to self-assemble into well-defined nanostructures in aqueous solution. The main focus of this work is to understand the impacts of polymer topology on self-assembly behavior and response to external stimulus, particularly pH. Poly(L-lysine) and poly(L-glutamic acid) are two pH-responsive, hydrophilic polypeptides that possess the unique property of undergoing α-helix to random coil secondary structure transitions with pH, and this responsiveness can lead to global morphology changes such as changes in aggregate size or even morphology transitions. These polypeptides are synthesized via ring opening polymerization of N-carboxyanhydrides (ROP of NCAs), and a combination of different reactive initiators and efficient coupling chemistries are used to develop systems with different topologies. Three topologies that will be discussed in this dissertation are AB2 star, ABA linear triblock, and BAB linear triblock copolymers. Significantly, our work on polypeptide-based AB2 star polymers, often referred to as lipid mimetics given their structural resemblance to phospholipids, has identified that many different hydrophobic B moieties can be covalently linked to a polar, hydrophilic polypeptide to result in polymeric molecules that spontaneously assemble into well-equilibrated vesicle bilayers; changes in vesicle size and chain density at the vesicle interface result through helix-coil transitions of the polypeptide. Both ABA and BAB linear triblock copolymers express dynamic aggregation behavior through morphological transitions (i.e., spherical micelle-to-vesicle) with pH, and we identify that these transitions are experienced around the helix-coil transition of the polypeptide. We further demonstrate temperature responsiveness of linear triblock copolymers by employing hydrophobic B blocks that show a lower critical solution temperature (LCST). We employ a combination of light scattering and microscopy techniques, as well as circular dichroism (CD) spectroscopy to gain an in-depth understanding of self-assembly properties. The unique self-assembly properties that we have identified for these polypeptide hybrid block copolymers are proving useful in the area of controlled drug delivery vehicles. We show that the responsive nature of these assemblies can be used to tune release of doxorubicin hydrochloride (Dox HCl), a chemotherapeutic, at different pH and salt concentrations.

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