THESIS
2001
xiii, 91, [35] leaves : ill. ; 30 cm
Abstract
Photodynamic therapy (also called PDT, photoradiation therapy, phototherapy, or photochemotherapy) is a very promising therapy and a new modality for cancer control. It is based on the discovery that certain chemicals known as photosensitizing agents (e.g. Photofrin® II, a hematoporphyrin derivative (HPD)) can selectively accumulate in tumor tissues, which activate oxygen molecule to become cytotoxic species upon irradiation. PDT destroys cancer cells through the use of a fixed-frequency laser light in combination with a photosensitizing agent. However, the first generation photosensitizer, hematoporphyrin derivatives (HPD), is a complex mixture and it has rather weak absorptivity in the red region of visible spectrum, a region with good tissue penetration. Recently, attempts have been...[
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Photodynamic therapy (also called PDT, photoradiation therapy, phototherapy, or photochemotherapy) is a very promising therapy and a new modality for cancer control. It is based on the discovery that certain chemicals known as photosensitizing agents (e.g. Photofrin® II, a hematoporphyrin derivative (HPD)) can selectively accumulate in tumor tissues, which activate oxygen molecule to become cytotoxic species upon irradiation. PDT destroys cancer cells through the use of a fixed-frequency laser light in combination with a photosensitizing agent. However, the first generation photosensitizer, hematoporphyrin derivatives (HPD), is a complex mixture and it has rather weak absorptivity in the red region of visible spectrum, a region with good tissue penetration. Recently, attempts have been made to improve the efficacy of in vivo photosensitizers by utilizing purer and well characterized materials.
To develop so-called second generation photosensitizers for PDT, different derivatives of chlorin and benzochlorin mononers which exhibit absorption maxima covering the region between 650 to 840 nm have been synthesized in high yields by introduction of electron-withdrawing and donating groups on the chromophore and by expanding the π-conjugation of the macrocycle.
In this thesis, monomeric and dimeric benzochlorin derivatives have been prepared to contain functional groups as well as to improve absorption in longer wavelengths. To study the localization and photodamage mechanism of photosensitizer in tumor cells, several cationic benzochlorin and chlorin imidinium salt have been prepared in high yields.
Photodynamic activities of these compounds have been screened on nasopharyngeal carcinoma (NPC) cells. The cationic photosensitizers particularly, gave promising results on in vitro NPC cells in terms of their photocytotoxicity.
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