Date of Award

2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

David P. Cormode

Abstract

Cancer is the leading cause of death globally and was responsible for an estimated 9.6 million deaths in 2018. Depending on the type and stage of cancer, treatments to eradicate the tumor or slow its growth include surgical intervention, chemotherapy, radiation therapy, immunotherapy, but these treatments may result in severe side effects,. Local sustained and controlled release of these therapeutic agents can significantly improve therapeutic efficacy and alleviate side effects. To achieve local controlled therapeutics release, novel drug delivery systems for the combination of cancer therapies need to be developed, and hydrogels are an attractive vehicle for this purpose. Hydrogels are three-dimensional hydrophilic polymeric networks that can swell with water. Their porosity permits loading of drugs and other cargoes into the gel matrix. One of the most significant developments of hydrogels is the emergence of stimuli-responsive hydrogels. Hydrogels can be designed to be injectable and formed in situ upon temperature changes or be stimuli-responsive serving as an on-demand drug delivery platform, allowing clinicians to modulate the timing and extent of drug release and plan for cancer treatment regimens, such as radiotherapy or immunotherapy. Thus, we herein propose the development of thermosensitive tumor casting hydrogels for treatment of hepatocellular carcinoma, and FLASH radiotherapy responsive hydrogels for immunotherapy of melanoma,Unfortunately, hydrogels present challenges when attempting to assess their properties in tissue, as crucial information involving hydrogel administration site and degradation degree is often lacking. To address this issue, evaluating and monitoring hydrogels with noninvasive imaging modalities is on the rise. Therefore, we incorporated gold nanoparticles (AuNP) into the previously mentioned hydrogels making them radiopaque. We recently surveyed elements that could potentially be used as SPCCT contrast agents and discovered that ytterbium can produce twice the contrast of the element most used for CT and SPCCT contrast agents, gold. Therefore, finally, we developed ultra-small ytterbium nanoparticles that can be used as contrast agents for both CT and SPCCT and can be used in the hydrogel system.

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