Date of Award
2024
Degree Type
Dissertation
Degree Name
Doctor of Philosophy in Physics
Specialization
Applied Physics
Department
Physics
First Advisor
Oleg Andreev
Abstract
The most common cancer treatments are chemotherapy and radiation therapy which include an untargeted delivery of toxic molecules, resulting in systemic effects and reduction in patient comfort. This leads to research for cancer treatments that are targeted and will reduce the severity of systemic effects on patients. Tumor resection surgery also has its own complications relating to not having real time confirmation of tumor geometry and position. pHLIP peptide targets acidity which is a characteristic of most cancer lines due to the Warburg effect, along with targeting tumor associated macrophages, cancer associated fibroblasts, and myeloid derives suppresser cells that are present in the tumor micro environment. This targeting mechanism has been used to deliver foreign antigens, cytotoxic molecules, immunomodulators, and fluorophores to tumor sites. In vitro experiments to test cargo molecules were done on three dimensional tumor spheroids using confocal microscopy. In vivo experiments with the cargo molecules were done on mice by measuring tumor size, mouse weight, and performing NIR imaging. Ex vivo experiments with the cargo molecules were done with collected tumors and organs from mice using enzyme linked immunosorbent assays, histology, and immunohistochemistry. Foreign antigen delivery to tumors has shown a 50% reduction in tumor size, when administered after immunizing against the specific antigen. Immunomodulator delivery has shown a 100% reduction in tumor size and immune memory to the originally administered cancer cell line. Cytotoxic molecule delivery has shown a change in the cellular composition of the tumor micro environment, which can lead to a higher immune activation for subsequent therapy. Fluorescent molecule delivery has shown to give real time continuous imaging of tumors for resection surgery. The mentioned therapy approaches have shown little or no systemic effects to the live subjects, and present alternatives to chemotherapy or radiation therapy. The delivery of fluorescent molecules has shown to be useful as an additional confirmation to surgeons during tumor resection.
Recommended Citation
DuPont, Michael, "DESIGN AND APPLICATION OF PH SENSITIVE PEPTIDES FOR FLUORESCENCE IMAGING AND THERAPY OF TUMORS" (2024). Open Access Dissertations. Paper 1644.
https://digitalcommons.uri.edu/oa_diss/1644