Date of Award

12-31-2016

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Physics, Applied

First Advisor

Jonathan Celli

Second Advisor

Stephen Arnason

Third Advisor

Chandra Yelleswarapu

Abstract

The global disparities in cancer outcomes lead to inequality of effective therapeutics between developing and developed countries. In this context, the potential role of photodynamic therapy (PDT), is considered. PDT is a light-based modality, in which wavelength-specific activation of a photosensitizing molecule leads to site-directed tumor destruction. This general approach has exhibited safety and clinical efficacy at various sites, including in the oral cavity. However, in considering the context of cancer treatment technologies suitable for resource-limited setting, it needs to satisfy several additional requirements. All enabling devices should be low-cost, robust and portable devices with stable operation on battery power, simple to operate interfaces, and with potential for telemedicine integration. A prototype LED-based PDT light device satisfying these design constraints was developed and updated recently This thesis describes a series of laboratory-based experiments to evaluate the performance of this new low-cost PDT device and specifically explores certain challenges and determinants of PDT efficacy particularly important to the envisioned application for treatment of oral malignancies in a resource limited environment. Through the treatments on monolayer cell cultures of A431 squamous carcinoma cells, which photosensitized by administering aminolevulinic acid (ALA) to induce the accumulation of protoporphyrin IX (PpIX), we focused on the efficacy of the low-cost LED-based light sources to achieve cell death, compared the efficacy of continuous irradiation and fractionated irradiation at the same dose. In this research, decreased viability was obtained with increased irradiation dose and nearly complete cell death at 80J/cm^2. We also demonstrated fractionated irradiation, which divided the light dose into fractions by pausing the light source for a certain time, is more efficient than continuous irradiation at the same dose, for the viability of cells with fractionated irradiation was lower than the same dose achieved with continuous delivery. In these results, we also observed the viability is associated with the cell density, and constructed reasonable explanations based on the literature review. This research showed potentiality of the LED-based device with the real clinical practice for the ALA induced PDT treatment.

Comments

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