LE3 .A278 2010

2010

Lukeman, Matthew

Acadia University

Bachelor of Science

Honours

Chemistry

Chemistry

Two- Photon Excitation Photodynamic Therapy ( TPE- PDT) is a novel extension of traditional photodynamic therapy techniques. Traditional One- Photon Excitation ( OPE) PDT utilizes a combination of light, oxygen, and a photosensitizer to induce cellular death. Ideal photosensitizing drugs accumulate preferentially in problem tissues and generate reactive singlet oxygen with light activation, ultimately leading to cellular apoptosis. Photodynamic therapy has been used successfully in treatment of age- related macular degeneration ( AMD) and soft- tissue cancers. In AMD, small blood vessels grow out of the choroid and into the retinal space, causing structural damage to the macula and vision loss. Photodynamic therapy can be used to stop the growth of these blood vessels and minimize vision loss caused by angiogenesis. Problems arise when photosensitive drugs are activated in areas adjacent to the treatment area. The use of TPE- PDT alleviates this problem by making use of two lower energy photons to cause similar excitation. Two- photon excitation is dependent on the square of the laser beam intensity, and is most efficient at the focal volume of a highly focused laser beam. Thus, there will be less collateral damage to the surrounding tissue. One photosensitizing agent commonly used is verteporfin, a benzoporphyrin derivative known commercially as Visudyne( R). Lemuteporfin, a photosensitizing agent similar in structure and function to verteporfin, is currently being investigated as a potential alternative for use in TPE- PDT. In an attempt to characterize differences between the photosensitizers, photobleaching and quenching experiments were x performed in multilamellar vesicles, unilamellar vesicles, and U343 glioblastoma cells. Results from these experiments show that lemuteporfin differs from verteporfin in its position in cellular membranes, sitting farther into the non- polar region of the membrane. This positioning difference may allow it to have greater access to molecular oxygen, leading to an increased ability to generate singlet oxygen.

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https://scholar.acadiau.ca/islandora/object/theses:707