Creating innovative bio-convergent technologies for better human life

bioeng_admin 2005-08-23 21:14:21
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Title: In vivo photodyanmic therapy of cancer with protease activated photosensitizing beacon.

Speaker : Yongdoo Choi, Ph.D
Center for molecular Imaging Research, Harvard medical
school, USA.
Place : Room 219, Jung-Moon Soul Building
Time : 4:00 pm, Tuesday, August 23rd
Abstract:

Photodynamic therapy (PDT) is a relatively new modality for the treatment of cancers and other non-malignant conditions. It involves the administration of a photosensitizing agent, usually a porphyrin-based compound, and subsequent illumination of the tissue by a visible, non-thermal light source of the appropriate wavelength (400-760 nm). This light exposure excites the photosensitizer, which is then able to interact with its surroundings. In oxygenated environments, the energy of the excited state is often dissipated by transfer to molecular oxygen, which leads to the formation of the highly reactive and cytotoxic singlet oxygen species. When this process occurs within tissues, it results in cellular damage. Since this effect is observed only in the presence of light, PDT is locally selective, thereby reducing damage to the surrounding healthy tissue. When injected, porphyrin-based photosensitizers are found to be taken up by malignant or dysplastic tissues with some selectivity; however, the hydrophobic nature of photosensitizers often cause them to accumulate in healthy tissues, resulting in prolonged photosensitivity. Skin and eye photosensitivity have been observed in clinical trials, requiring that patients avoid exposure to sunlight for several weeks or months.

Therefore, we developed a protease-triggered photosensitizing beacon. By using this new design, near-infrared fluorescence (NIRF) and singlet oxygen generation (SOG) from chlorin e6 were quenched until the peptide linker is cleaved by a cathepsin B, which is overexpressed in cancers. After enzymatic activation, NIRF and SOG were increased again about 5 times. Results from in vivo animal study also suggested quenching and dequenching of singlet oxygen generation.