Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Dr. Elizabeth R. Gillies

Abstract

Polymersomes are potentially multifunctional soft materials constructed by the self-assembly of amphiphilic block copolymers in aqueous medium. While much research has focused on controlling the assembly and encapsulation properties of polymersomes, their surface functionalization has been relatively unexplored. This is important because it plays a critical role in determining their properties such as toxicity and biodistribution behavior. The work described in this thesis involves the development of a biocompatible and biodegradable polymersome systems based on poly(ethylene oxide)-b-polycaprolactone (PEO-PCL) block copolymers with azide surface groups as a novel scaffold for various biomedical applications. The surface functionalization of these polymersomes with polyester dendrons bearing alkyne focal points with different peripheral groups, such as amines and guanidines, as well as a small molecule rhodamine dye is accomplished and their conjugation yields are compared to each other. Moreover, dendritic and non-dendritic polymersome-based MRI contrast agents, with the highest currently reported longitudinal relaxivity for a polymersome system, are developed by decorating PEO-PCL polymerosomes' surfaces with both non-dendritic and dendritic Gd(III)-based contrast agents. In addition, PEO-PCL polymersomes were employed to develop a multifunctional system with the potential to interfere with the viral infection process at two levels. In addition to their use as materials for functionalizing the surfaces of nanomaterials, dendrimers and their assemblies have been widely used as drug delivery vehicles. In order to enable a new level of control over drug release, backbone photodegradable dendrimers and dendrons are synthesized by incorporation of a monomer unit based on o-nitrobenzyl esters and 2,2-bis(hydroxymethyl)propionic acid. It is shown that these dendrimers undergo effective photolysis to release only small molecules upon irradiation with UV light. Finally, these dendrons are incorporated into amphiphilic Janus dendrimer structures and their self-assembly to dendrimersomes followed by their photodegradation are discussed.


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