Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/191
Title: Cellular Uptake and Distribution of Zn(II) N-alkylpyridylporphyrin-based Photosensitizers – Effect of Hydrophobicity
Authors: Rema Abdlgany ريما عبدالغني عزالدين 
Supervisor: د. ليدميل بينوف
Keywords: Photosensitizers Hydrophobicity Zn(II) N-alkylpyridylporphyrin Photodynamic therapy
Issue Date: 2012
Publisher:  Kuwait university - college of graduate studies
Abstract: Photodynamic therapy (PDT) is an approved, minimally invasive therapeutic modality used for the management of a variety of cancers and benign diseases. The approach is based on the use of visible light to activate a light-absorbing compound (photosensitizer), which in the presence of molecular oxygen leads to the generation of singlet oxygen and other reactive oxygen species. These cytotoxic species damage and eventually kill target cells. Development of new photosensitizers with properties optimized for PDT applications is crucial for improvement in therapeutic efficiency of PDT. Zn(II) N-alkylpyridylporphyrins act as photosensitizers and kill cancer cells as well as antibiotic-resistant pathogenic bacteria. These zinc porphyrins are meso-substituted and chains are attached to the N-pyridyl moiety of the macrocycle. The aim of the study was to investigate how modifications at the periphery of ortho, meta and para Zn(II) N-alkylpyridylporphyrins affect their cellular uptake, sub-cellular distribution, biological effects and photodynamic efficacy using an LS174T adenocarcinoma cell line as a model system. Upon light activation Zn(II) N-alkylpyridylporphyrins produced profound cytotoxic effects on cancer cells and inhibited cellular metabolism and proliferation. Cell death was mediated by the apoptotic pathway. These effects were absent when cells were incubated with the compounds in the dark. Increasing the hydrophobicity of Zn(II) alkylpyridylporphyrins by increasing the length of the peripheral hydrocarbon side chains resulted in increased bio-efficiency, cellular uptake and ability to induce cell death. Bio-efficiency and subcellular distribution were also influenced by structural differences between ortho, meta and para isomers. The amphiphilic hexyl derivatives of Zn(II)porphyrins were found to localize to membranous organelles including mitochondria, the endoplasmic reticulum and lysosomes, as well as the plasma membrane. These results indicate that Zn(II) N-alkylpyridylporphyrins have great potential as photosensitizers for photodynamic therapy.
URI: http://hdl.handle.net/123456789/191
Appears in Programs:0540 Medical Biochemistry (M.Sc.)

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