Date of Award

12-14-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Applied Science

First Advisor

Alexandru Biris

Abstract

The American Cancer Society has predicted an estimated 281,550 new invasive breast cancer cases for 2021. Chemotherapy is one of the main options available to treat this disease, but it can result in drug resistance and harmful side effects, as traditional methods do not directly target the cancer cells. To address this issue, nano formulations have been widely researched for targeted delivery of anticancer drugs. The primary objective of this project was to develop a novel nanodrug, rapamycin-loaded gold nanorods functionalized with polyethylene glycol and epithelial cell adhesion molecule (EpCAM), to selectively target breast cancer cells. The work involved characterizing and testing the toxicity of the nanorods, as well as optimizing the working dosage and timeframe for treatment using cytotoxicity (MTT) and flow cytometry assays. Transmission electron microscopy was used to analyze the mechanisms by which the breast cancer cells took up the nanorods and the nanorods’ localization in intracellular compartments. The cells were exposed to known inhibitors of endocytosis, then the uptake of gold was analyzed using ICP-MS. The amount of gold taken up was quantified in picograms per cell. The nanosystem’s pharmacokinetics was determined by analyzing the mechanism of action of rapamycin, an FDA approved drug, calculating the drug loading efficiency, and studying the release profile under different pH conditions (acidic and neutral). Proliferation assays were conducted with both the novel nanodrug and the free drug to test their toxicity and efficacy. Targeting assays were conducted to compare the efficacy of the nanodrug in cancer cell lines and non-cancer cell lines. Our results are promising but expectations for novel nanodrugs must remain realistic, as they face challenges like potential cytotoxicity, better characterization, considerable cost, and the need for clinical trials.

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