Synthesis, solution assembly, and characterization of amphiphilic block polymers

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University of Delaware
Analogous to small molecule lipids and surfactants, amphiphilic block polymers self-assemble into well-defined nanostructures in aqueous solutions such as spherical micelles, cylindrical micelles, and vesicles. Their macromolecular architecture leads to several advantages compared to small molecule amphiphiles, including increased chemical versatility, explicit control over the size and structure of solution assemblies, extremely low critical aggregation concentrations, and exceptionally slow chain exchange. These attractive advantages have motivated significant research efforts towards developing polymeric surfactants for emerging nanotechnologies including aqueous nanoreactors and drug delivery vehicles. To take full advantage of block polymer materials in these applications, a comprehensive understanding of the factors that influence self-assembly behavior as well as robust methods for controlling the chemical functionality of polymeric assemblies must continue to be developed. Accordingly, this dissertation demonstrates the synthesis, solution assembly, and characterization of amphiphilic block polymers towards the goal of creating well-defined nanoassemblies. The first objective of this dissertation was to systematically investigate the effects of common processing conditions on the structure, dynamics, and long-term stability of block polymer micelles. The pronounced effects of organic cosolvent addition and subsequent removal were studied using a combination of cryogenic transmission electron microscopy and small angle neutron scattering. Notably, solution agitation was found to have unexpected consequences on the dynamics and stability of the resulting assemblies. A growing number of works indicate that in addition to the structure, the chemical functionality of polymeric assemblies plays a critical role in determining the in vivo fate of drug delivery vehicles. Thus, the second objective of this research was to establish a tunable method for controlling the display of peptide groups within polymeric assemblies to target specific diseased tissues. A modular synthetic strategy was developed for creating well-defined polymer-peptide conjugates that allowed control over both the peptide sequence and peptide location within the polymer backbone. Together, the efforts in this dissertation provide the foundation for the rational design of novel materials by enabling greater control over both the structure and functionality of polymer-based nanoassemblies.