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Title: Effect of Spatial Distribution of Substituent on Cellular Uptake, Distribution, and Photo-efficiency of Porphyrin-based Photosensitizers
Authors: Maha Abdul Azeez Al-Habeeb 
Supervisor: Prof. Ludmil Benov
Degree Awarded: M.Sc. Degree in: Medical Biochemistry
Keywords: Photodynamic therapy : Zn(II) N-alkylpyridylporphyrins : metal-free photosensitizers : NADH photo-oxidation : PS photo-modifications
Issue Date: 2019
Publisher:  Kuwait university - college of graduate studies
Abstract: Photodynamic therapy (PDT) is a relatively noninvasive therapeutic option for the treatment of malignant and nonmalignant diseases. Because reactive species generated through PDT are short-lived, efficacy of PDT depends on reactive species quantum yields and cellular location of the PS. NADH plays a key role in cell metabolism and its photooxidation will have deleterious consequences for cells targeted by PDT. The aim of this thesis was to investigate how the three-dimensional structure, charge, lipophilicity and size of tetra-cationic Zn(II) meso-tetrakis (N-alkylpyridinium-2 (or-3 or-4)-yl) (ZnPs) porphyrins and the metal-free ligand PSs, affect their photo-physical and photo-chemical properties, the photo-oxidation of NADH, the cellular uptake and subcellular distribution. Rates of 1O2, NADH photo-oxidation, and photo-degradation of PSs were determined using UV-VIS spectroscopy. The PSs efficiency for PDT was investigated through cytotoxic and anti-proliferation effects, in vitro, using MTT and SRB viability assays on a human breast cancer cell line (MDA-MB-231). No differences between the photoinduced generation of 1O2 by the ZnP and the metal-free ligand PSs were seen. The rate of NADH photo-induced oxidation varied depending on the tested ZnPs. NADH photooxidation by ZnPs were higher in dimethylformamide (DMF) than in aqueous solvents. Generally, ZnPs and H2TM-PyPs caused lower rates of NADH oxidation in the presence of singlet oxygen (1O2) scavengers. Surprisingly, presence of L-histidine accelerated NADH oxidation, suggesting the possible generation of other ROS and/or free radicals. ZnPs were more susceptible to photo-induced modifications/bleaching than H2TM-PyP. Increasing the concentration of ZnPs protected them from photo-degradation. MDA-MB231 cellular viability and proliferation were greatly imposed by the 3D shape of the amphiphilic PSs. Cellular distribution of the amphiphilic asymmetric H2TriBu-3-PyPMPhOC12P showed different subcellular distribution than the amphiphilic symmetric H2TnBu-3-PyP analogue
Appears in Programs:0540 Medical Biochemistry (M.Sc.)

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