Date on Master's Thesis/Doctoral Dissertation

8-2018

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

O’Toole, Martin

Committee Co-Chair (if applicable)

Malik, Tariq

Committee Member

Malik, Tariq

Committee Member

Clark, Geoffrey

Committee Member

Frieboes, Hermann

Committee Member

Steinbach-Rankins, Jill

Author's Keywords

MRI; AS1411; cancer; contrast agent

Abstract

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable contrast agent for detection and monitoring of malignancies by MRI. The gold nanoparticle core (GNPs) enhances the pharmacokinetic properties of the proposed contrast agent, increases its potency, and provides a good way to co-localize the aptamer with the contrast agent. AS1411 is anti-nucleolin aptamer that binds to nucleolin protein, which is highly expressed in cancer cells, leading to selective accumulation in cancers cells. The ability of the proposed contrast agent to target cancer cells and enhance MRI contrast was assessed using MDA-MB-231 triple negative breast cells and MCF-10 human mammary epithelial cells. Moreover we assessed the biodistribution and toxicity of the proposed contrast agent in vivo. The results presented in this thesis demonstrate the superiority of the proposed contrast agent with respect to the current commercial contrast agents (e.g., MultiHance).

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