Date of Award

12-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Committee Chair/Advisor

Dr. Luigi Boccuto

Committee Member

Dr. Valery Bliznyuk

Committee Member

Dr. Brian Booth

Committee Member

Dr. Diana Ivankovic

Abstract

This dissertation explores the development and evaluation of small molecule photosensitizers used in photodynamic therapy (PDT) for cancer treatment. It comprises three studies that address distinct stages of the drug development pipeline. The first is a literature review assessing the utility of zebrafish as an in vivo model for PDT research. The review highlights the versatility of zebrafish xenograft and transgenic tumor models in evaluating both therapeutic efficacy and toxicity of photosensitizers. The second study presents a pilot investigation using the Biolog Phenotype MicroArray for Mammalian cells (PMM) platform to assess metabolic changes in cancer cells following PDT exposure. Although limited by sample size, the study demonstrates the platform’s potential to detect glycolytic impairment post-treatment. The third study examines the ethical considerations of accelerating phase I cancer drug trials by drawing parallels with the expedited clinical trial processes used during the COVID-19 pandemic. Applying the ethical framework proposed by Emanuel, Wendler, and Grady, the analysis concludes that while such acceleration was justified in the context of a global viral pandemic, the same rationale does not extend to cancer therapeutics due to differences in disease dynamics and treatment applicability. Collectively, these studies contribute to a more nuanced understanding of preclinical modeling, metabolic assessment, and ethical trial design in the context of small molecule cancer drug development.

Author ORCID Identifier

0009-0001-3067-1249

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