Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Abstract

Photodynamic therapy (PDT) is used to treat cancer, and involves a highly conjugated molecule, called a photosensitizer (PS), which is excited by wavelengths of light from visible to infrared. Photosensitizers that are highly conjugated will absorb longer wavelengths (600 – 900 nm), and have the potential to destroy cells of deeper tissue cancers. In PDT, a PS is administered to the patient, and after an appropriate time delay, the tissue is then exposed to light of a specific wavelength necessary for excitation of the PS. A transfer of energy can take place between the excited PS and oxygen that is nearby. This process allows the PS to relax back to the ground state, while creating an excited singlet state oxygen molecule (1O2).

Buchwald-Hartwig conditions using Pd catalysts and phosphorus containing ligands can be utilized to synthesize the photosensitizer. The reaction involves a Pd-catalyzed cross coupling of an aryl halide with a nitrogen nucleophile to form a new carbon-nitrogen bond. The PS will be PEGylated with an amine–PEG–Folate complex. Since many tumors over-express folate receptors, the PS–PEG–FA complex will be transported to cancer cells via receptor mediated endocytosis, providing greater selectivity.

The killing efficiency of the PS will be tested using HeLa cells. Solutions

containing PS only, PS–PEG–FA, and media only will be added to cancer cells with folate restricted media. After exposure to light, the cells will be counted to determine the percentage of cells killed by the singlet oxygen and other radical species. Variables that must be controlled in this study are the following: length of time cells have been growing; specific concentration of PS–PEG–folate complex; length of time for PS–PEG–folate complex uptake into the cell; length of time of exposure to light; length of time from light exposure to cell counting to determine necrosis. The goal of the research is to determine the concentration of PS and length of time of light exposure that is maximally effective for killing tumor cells.

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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