Semester

Fall

Date of Graduation

2022

Document Type

Dissertation

Degree Type

PhD

College

Statler College of Engineering and Mineral Resources

Department

Chemical and Biomedical Engineering

Committee Chair

Margaret Bennewitz

Committee Co-Chair

Robin Hissam

Committee Member

Robin Hissam

Committee Member

Timothy Eubank

Committee Member

Yuxin Liu

Committee Member

Xueyan Song

Abstract

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide nanocrystalline cores and encapsulating them within biodegradable polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Both the cores and NEMO particles were rigorously characterized for size, charge, chemistry, pH-sensitive degradation, stability, and MRI signal. At pH 7.4 mimicking blood, NEMO particles were intact, and no MRI signal was detected (“OFF”). When the pH became acidic mimicking cancer endosomes (pH 5), NEMO particles dissociated to release Mn2+ ions and created a robust MRI signal (“ON”). After characterizing the particles, a tumor-targeting peptide against underglycosylated mucin-1 (uMUC-1) was attached through click chemistry. Cellular uptake, viability, and MRI properties were studied in different breast cancer cell types compared to control mammary cells to evaluate NEMO particle specificity and toxicity. Lastly, a breast cancer mouse model was utilized to compare the novel NEMO particle contrast agent to gold standard gadolinium chelates. MRI signal enhancement, organ retention, and overall toxicity were examined to show the superiority of tumor-targeted NEMO particles over gadolinium chelates. The underglycosylation of MUC-1 is present in other cancers such as pancreatic and colorectal, making NEMO particles easily applicable for the detection of malignancy beyond breast cancer. Due to their binary readout, NEMO particles are anticipated to streamline and simplify cancer diagnosis.

Embargo Reason

Publication Pending

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