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Title: Mitochondria-targeting Properties and Photosensitizing
Authors: احمد محمد عودة AHMED OUDAH 
Supervisor: د. جيمس كريك
Keywords: Photosensitizing Photosensitizers
Issue Date: 2012
Publisher:  Kuwait university - college of graduate studies
Abstract: Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic modality for treatment of tumors and certain benign diseases. In PDT, destruction of cells and tissues is achieved by administration of a photosensitizing agent (PS) followed by irradiation with light of appropriate wavelength. In the presence of oxygen, illumination results in production of cytotoxic reactive species. PDT works through three key mechanisms: direct killing of cells, damage to microvasculature, and induction of local inflammatory reactions. Mitochondria perform vital cellular functions and play a key role in regulating apoptotic cell death, which makes those organelles a promising target for increasing PDT efficiency. Since most reactive species generated by excited PSs have a short life in the biological environment, PS localization is a key factor determining PDT outcome. Localization, in turn, depends on the properties of the PS molecule. The aim of this project was to investigate how changing the structure of Zn(II) meso-tetrakis(N-alkylpyiridinium)porphyrin (ZnP) PSs would affect their mitochondrial targeting capabilities and PDT efficacy, and to identify potential mitochondrial targets. Increasing the lipophilicity of the ZnP molecule by attaching an aliphatic chain of six carbons at the periphery of the porphyrin ring increased the efficiency of the PS. The amphiphilic hexyl ZnP analog was the most efficient in suppressing cellular metabolism and mitochondrial respiration. Potential mitochondrial targets for ZnPs were NADH and NADPH, cytochrome c (a small mobile electron carrier), cytochrome c oxidase (a large transmembrane protein complex of the mitochondrial respiratory chain), and mitofilin (a mitochondrial structural protein). This study demonstrated that modifying the periphery of a positively charged ZnPs by attaching aliphatic chains with appropriate length produced efficient, amphiphilic, mitochondria-targeting PS.
Appears in Programs:0540 Medical Biochemistry (M.Sc.)

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