Date of Award

8-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioengineering

Committee Chair/Advisor

Brian W. Booth

Committee Member

Delphine Dean

Committee Member

Heather Dunn

Abstract

About 10–15% of all instances of breast cancer are triple-negative breast cancer (TNBC). TNBCs are not responsive to hormonal or anti-HER2 treatments since they lack estrogen and progesterone receptors and have low levels of HER2. TNBC is a highly aggressive subtype of breast cancer and has a prognosis often worse than that of other subtypes. Usually, chemotherapy and surgery are combined since this is a very efficient way to remove tumors. Chemotherapy medications that effectively remove cancer cells may adversely affect healthy cells and have severe repercussions, which can impair patients' psychological and quality of life (QOL). To reduce adverse effects, enhance patient quality of life, and preserve therapeutic efficacy, a more targeted therapy approach for TNBC should be investigated.

Magnetic hyperthermia (MHT) is a passive-targeting, minimally-invasive treatment for TNBC that minimizes the requirement for other severe well-established therapies having both short- and long-term toxicities for patients. MHT involves heating magnetic nanoparticles in an alternating magnetic field (AMF) to heat local tissues/cells without killing normal epithelial cells since they show better resistance to temperature than the tumor ones. The magnetic nanoparticles used must meet many criteria to be effective in the treatment: they must be small, weakly agglomerated, and possess particular superparamagnetic behavior. Considering these criteria, superparamagnetic polymer nanocomposite (PNC) was synthesized by the thermal decomposition method and coated with nirtroDOPA-modified polyethylene glycol (PEG) that will efficiently heat up, resulting in self-controlled magnetic hyperthermia and the death of the cancer cells under the influence of an alternating magnetic field.

The aim of this study was to find the optimal dosage of polymer nanocomposite for magnetic hyperthermia therapy of the TNBC cell line, MDA-MB-231, with the least amount of harm to the human breast epithelial cell line, MCF10A. Prussian blue staining suggests 30 minutes is an adequate time for PNC to get internalized in the cell cytoplasm, and the particles are retained by cells for up to 72 hours. Magnetic hyperthermia treatment was carried out by treating cells with polymer nanocomposite and then applying an alternating magnetic field (AMF) at a frequency of 205 kHz and a field intensity of 24 kA/m for 30 minutes. Following statistical analysis of cell counts and MTT assay, polymer nanocomposite concentrations 0.025 µg/ml and 0.1μg/ml were found to be the most effective in treating TNBC via magnetic hyperthermia treatment. These concentrations were the least cytotoxic for both cell lines and effectively resulted in cell mortality exceeding 50% during magnetic hyperthermia therapy. Annexin V-FITC/PI staining confirmed early apoptosis to be the mode of cell death triggered by magnetic hyperthermia treatment. Co-cultures further prove that magnetic hyperthermia treatment is more effective against TNBC cells, while normal breast epithelial cells show better resistance to heat. In conclusion, the investigated polymer nanocomposite has shown strong anticancer activity and satisfactory performance under alternating magnetic fields in vitro, making it deserving of more research as a potential alternative therapy for triple-negative breast cancer.

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