Graduate Thesis Or Dissertation
 

Investigating Multimodal Therapies with Nanotechnology to Engineer Advanced Chemoradiation Platforms

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/df65vf891

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  • The potential for nanomedicine to reduce toxicity and improve therapeutic response to radiation is vast. Clinically, this potential has thus far only begun to be realized with the recent success of the radioenhancing nanoparticle, NBTXR3 by Nanobiotix. Radioenhancing nanoparticles, however, represent only a small class of nanomaterials that may be impactful in the field of radiation therapy. In addition to radioenhancing nanoparticles, there are drug-carrying nanoparticles that may produce improved responses by safely and more effectively delivering toxic chemotherapeutics to the target site. At the interface between these classes of particles are those which would provide benefits in both categories, dose-enhancement and drug-delivery. Clearly, there is a plethora of nanoparticles that may change the current radiotherapy paradigm for the better. In this thesis, we investigate the potential to translate drug-carrying and radioenhancing nanoparticles for use in clinical radiotherapy. First, we address the issues unique to the use and implementation of drug-carrying nanoparticles for chemoradiation. After presenting these issues, we investigate the ability of dual drug-loaded micelles to enhance responses to chemoradiotherapy in a preclinical breast cancer model. With many variables, the nuanced nature of these multimodal therapeutic approaches demonstrate promise but also the need to properly define the appropriate treatment schedule, patient population, and combination of therapeutics for optimal efficacy and ease of clinical integration. Next, we expand our investigation to understand the complex interplay between radiation, tumor microenvironment, nanoparticle targeting, and therapeutic efficacy in a colorectal cancer model. We again demonstrate the importance of choosing not only an optimal treatment schedule for the chosen nanoparticle therapeutic, but also radiation therapy in order to obtain the best therapeutic response. Across all studies to comprise this dissertation, we demonstrate the utility of the PARP inhibitor Talazoparib in non-BRCA mutated cancers. Our results demonstrate the modular nature of nanoparticle therapeutic strategies and the success that can be achieved by carefully tailoring intelligent systems and treatment plans. We hope that this dissertation serves to spark new ideas and inspire further investigation of radiotherapy-nanomedicine from preclinical to clinical trials and ultimately to help patients.
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  • Pending Publication
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  • 2020-08-10 to 2022-09-11

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