Date of Award

5-16-2024

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Supervisor

Lisa Porter

Supervisor

Simon Rondeau- Gagné

Abstract

This thesis explores innovative nanoparticle systems designed for targeted therapy against CD44-expressing tumor initiating cells (TICs) in glioblastoma multiforme (GBM). First, we review the current literature on recent advancements in nanotechnology that exploit nanoparticles' unique properties for targeted treatment of CD44+ cells, potentially leading to more enhanced cancer treatments. Exploring lipid-based, polymer-based, and other nanoparticle types for targeted CD44+ cells. Next, investigate the development and analysis of diketopyrrolopyrrole(DPP)-based conjugated polymer nanoparticles (CPNs), which are modified with fluorescein(FITC)-conjugated hyaluronic acid (HA) to target CD44 receptors on TICs. These nanoparticles, HA-CPNs, are shown to penetrate the blood-brain barrier effectively, target CD44-positive TICs in a concentration and cell cycle phase-dependent manner, and impact key tumor properties such as stemness, invasiveness, and proliferation. After, we compare the properties and efficacy of FITC-conjugated CPNs with newly developed rhodamine (RHOD)-conjugated CPNs, focusing on their fluorescent properties, interactions with CD44 receptors, and potential anti-tumor effects in vitro. These studies highlight the selective uptake and localization of the nanoparticles, their impact on CD44 signaling and cell proliferation, and their toxicity levels toward normal neural cells. Overall, the thesis presents a promising new approach to targeting and treating resistant TIC populations in GBM, suggesting potential for these nanoparticles to contribute to more effective and personalized cancer therapy, and setting a solid groundwork for future clinical applications in nanomedicine for GBM.

Download

Included in

Biology Commons

Share

COinS