Hayley Parkin

Topic

Uniform, 1-Dimensional Polymer Nanofibers for Applications in Nanomedicine

Department of Chemistry

Date & location

• Tuesday, August 13, 2024
• 11:00 A.M.
• Elliott Building, Room 230

Examining Committee

Supervisory Committee

• Dr. Ian Manners (deceased), Department of Chemistry, University of Victoria (Supervisor)
• Dr. Cornelia Bohne, Department of Chemistry, UVic (Supervisor)
• Dr. Jeremy Wulff, Department of Chemistry, UVic (Member)
• Dr. Stephanie Willerth, Department of Mechanical Engineering, UVic (Outside Member)

External Examiner

• Dr. Hanadi Sleiman, Department of Chemistry, McGill University

Chair of Oral Examination

• Dr. Samira Gharehkhani, Department of Mechanical Engineering, UVic

Abstract

Polymer nanomaterials have garnered increased attention over the past several decades due to their ability to perform in a variety of applications, depending on the chemical functionality of the material used. Of note, polymers have been used increasingly for biomedical applications, from drug and gene delivery vehicles, to contrast agents and therapeutics themselves. Living crystallization-driven self-assembly (CDSA) provides a novel pathway for the preparation of morphologically pure, length-controlled, 1-dimensional (1D) polymer nanofibers. Thus, in this thesis, the applications of these nanofibers for applications in nanomedicine is explored.

Chapter 1 provides an introduction into polymer self-assembly, living CDSA, and the previous employment of nanoparticles for biomedical applications. Chapter 2 describes the synthesis and self-assembly of biodegradable and cationic poly(fluorenetrimethylenecarbonate)-block-poly(dimethylaminoethylmethacrylate) (PFTMC-b-PDMAEMA) 1D nanofibers, and evaluates the length and shape dependence on antibacterial activity against Escherichia coli. A comparison to neutral 1D poly(ethylene glycol) nanofibers is made. Chapter 3 then investigates the antibacterial mechanism of action of 1D nanofibers relative to nanospheres of identical composition. This pathway is explored through the use of confocal laser scanning electron microscopy and flow cytometry, as well as transmission electron microscopy and scanning electron microscopy. Chapter 4 expands upon preliminary drug-loading results to explore the addition of the anticancer therapeutic paclitaxel to the core-corona interface of PFTMC-b-PDMAEMA seed nanofibers. These are then evaluated as a delivery vehicle in 2D and 3D cell models containing glioblastoma cells. Chapter 5 then extends the scope of antibacterial activity of 1D PFTMC-b-PDMAEMA nanofibers against gram-positive Staphylococcus epidermidis, as well as explores the ability of these nanofibers for treating the extremely drug-resistant organism Burkholderia vietnamiensis. Chapter 6 concludes this thesis with an outlook as well as proposes future directions that could expand on the projects presented herein.