Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Determination of Therapeutic Effects of Multifunctional Antibody and Peptide Micelle-Based Nanocarriers on Breast Cancer Cells(01. Izmir Institute of Technology, 2021) Abdulhadi, Nusaibah Abdulsalam Abdulhad; Baran, YusufBreast cancer is the most prevalent type of cancer and a major cause of death among women globally. Currently, many treatments are developed to reduce breast cancer death risks. Targeting therapy represents an advanced and successful approach. It provides targeting specific tumor sites by using specific ligands and modifying physicochemical characterization of nanocarriers to increase drug efficiency. In this study, we aim to determine and compare the therapeutic effects of doxorubicin (DOX)- loaded nanocarrier that was synthesized by using two properties a core cross-linked and pH sensitivity to increase drug stability and DOX releasing at the tumor site. The effects of DOX-loaded micelles (DM), HER2 targeting peptide (LTVSPWY)-conjugated-DOX-loaded micelles (DMP), and antibody (Herceptin) conjugated-DOX-loaded-micelles (DMA) on HER2 positive SKBR-3 cell line and HER2 negative MCF-10A normal epithelial breast cell line were determined by using cytotoxic, apoptotic, cytostatic, and genotoxic assays. According to the cytotoxic assay, the IC50 value of DM, DMA, and DMP were 0.71-, 0.49-, 0.34-µM, respectively. Additionally, the fluorescence image showed higher DOX uptake by SKBR-3 cells treated with DMP. According to the apoptotic assays, the mitochondrial membrane potential on SKBR-3 cells with treated DMP decreased as well as higher apoptosis and necrosis rate that was regulated by Bcl-2, Pro-Caspase-3, PARP1, Bax, Bak, and Bcl-xL. Besides, the application of DMP caused cell cycle arrest at the G2/M phase. Lastly, DNA damage was observed in response to DMP determined by comet assay. This study provides a novel and effective therapeutic option for breast cancer through using this nanocarrier system with targeting properties.Master Thesis Assessment of Liposomal Formulations and Biological Activities of Eggplant Glycoalkaloids(Izmir Institute of Technology, 2019) Tatlıdil, Engin; Frary, AnneBillions of dollars are spent every year in the world for cancer treatments and research. In recent years, bioactive compounds are being tested as promising therapeutics. Among these compounds, eggplant glycoalkaloids: solasonine and solamargine are known to be effective against skin cancer and diseases. However, these compounds are water insoluble. This reduces transdermal drug delivery and the efficacy of solasonine and solamargine. Nanocarriers are used for transdermal drug delivery of water insoluble molecules. In this study, liposomes were used as nanocarriers to increase drug delivery of solasonine and solamargine. In the first stage of the study, empty liposomes produced from four different lecithin types with hydration temperatures of 40°C, 45°C and 50°C were evaluated according to their physical, chemical stability and drug loading capacity criteria at three different storage temperatures (4°C, 25°C, 37°C). The liposome formulation which was most suitable for the continuation of the study was determined. In the second stage of the study, solasonine and solamargine loaded liposomes were produced according to the formulation determined in the first stage and these liposomes were evaluated according to their physical, chemical stability, zeta potentials and drug leakage rate criteria for 3 months and it was determined that the drug loaded formulation was stable during the monitoring process. Furthermore, the release profiles of the drugs in different release media were determined and also the efficacy of the free and encapsulated states of solasonine and solamargine were tested in HaCaT and SCC-25 cell lines and IC50 values were determined.Master Thesis Determination of Therapeutic Effects of Multifunctional Micelle-Based Nanocarriers on Breast Cancer Cells(Izmir Institute of Technology, 2019) Ulu, Gizem Tuğçe; Baran, YusufBreast cancer is the most common and frequent cause of death among women composed to all types of cancer. Current treatment protocols do not provide complete cure or selective drug delivery while targeted therapy can provide an important avenue for successful treatment of breast cancer. In this study, therapeutic effects of drug-conjugated nanocarrier system with enhanced stability and double moiety pH-sensitivity on breast cancer (SKBR-3- HER-2- positive), normal breast epithelial (MCF-10A, HER-2-negative) and chronic myeloid leukemia (K562, HER-2-negative) cells were determined. With this approach, SKBR-3 cells were targeted by single nanocarriers having selectivity with unused peptide ligand (HER-2), stability with cross-linking of core moiety, and cleavage by two sites of pHeffect and drug release properties. After physicochemical characterization of micellebased nanocarriers, cytotoxic, apoptotic and cytostatic effects of doxorubicin conjugated micelles were determined. Doxorubicin conjugated micelles with HER-2 peptide (DOX-HER-2-NCs) had more cytotoxic effects on HER-2 positive cells. Additionally, intracellular amounts of doxorubicin is higher in SKBR-3 cells with applied DOX-HER-2-NCs as determined by fluorescence imaging. The apoptosis rate was increased on SKBR-3 at 50% cell growth inhibition (IC50) as determined by Annexin-V/Propidium iodide double staining. However, there was not any significant change in loss of mitochondrial membrane potential. Additionally, DOX-HER-2-NCs resulted in cell cycle arrest at G2/M-phase in response to IC50 value. Besides, protein level of Bcl-2 did not change while protein level of Bax and Caspase-3 were increased as determined by Western Blotting. This project provides novel and more effective treatment of breast cancer by using multifunctional properties of nanocarriers.Master Thesis Design and Preparation of Alkali Liposomes for Drug Delivery(Izmir Institute of Technology, 2019) Güven, Hatice; Özdemir, Ekrem; Altun, Zekiye SultanCancer is one of the deadliest diseases among other illnesses as an uncontrolled cell division. Liposomal technology has commonly been used in cancer therapy. Chemotherapeutical drugs, genetic materials, different imaging agents can be carried with liposomes. They are preferred by several important characteristics that selective passive targeting of tumors, increased stability and therapeutic index (reducing toxicity) via encapsulation and increased circulation life times with size adjustments. One of the indicator in cell cycle is intracellular pH. The aim of this study is to produce PEGylated alkali liposomes to provide cellular uptake in cancer cells and prevent cell division by changing of intracellular pH. Combination of liposomal technology and alkaline therapy in cancer cells may lead to the development of therapeutic strategies without using any drug to overcome chemoresistance and cell proliferation. For this purpose, alkali liposomes containing sodium carbonate (Na2CO3) solution were prepared and tested their effects on 4T1 breast cancer cell lines in vitro. The cell viabilities were evaluated using trypan blue and WST-1 methods. Pictures were taken for cancer cells to differentiate live and dead cells under different alkali liposome conditions for 5 days. It was found that cell medium containing alkali liposomes up to 3% didn’t affect cell growth. However, cell medium containing alkali liposomes greater than 7% significantly affected the 4T1 breast cancer cell growth and decreased the cell viability to about 40%. It was concluded that PEGylated alkali liposomes were prepared different concentrations to decrease or stop cell division of 4T1 breast cancer cell lines in vitro.Master Thesis Design of Micelle Embedded Chitosan Nanocomposites for Targeted Delivery of Hydrophobic Drugs(Izmir Institute of Technology, 2016) Cihan, Esra; Polat, HürriyetWhen successed to synthesize in a nanoparticulate form, chitosan has found to be a very effective biomaterial for drug delivery purposes owing to its extremely attractive characteristics such as its positive charge and pH sensitivity in aqueous medium. However, its structure as it is, is not suitable for oil soluble drugs. Even a close control on the size and shape of chitosan particles alone becomes a state of art and the production of chitosan nanoparticles is very difficult. Therefore, in this study, several methods were designed and used for synthesis of chitosan nanoparticles (<100 nm) with a hydrophobic core that are suitable for oil soluble drugs. Characterization of these nanoparticles were done by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Scanning Transmission Microscope (STEM), Transmission Electron Microscope (TEM), surface tension and zeta potential measurements. It was concluded that the best method was the coupling of drug loading with simple ionic gelation method among all the others. Hydrophobic drug loaded micelle embedded chitosan nano particles were able to manufactured successfully. The sizes of chitosan particles that embed Pluronic-123 micelles were larger (<100 nm) than the sizes of Pluronic-123 micelles (20 nm) alone. It was also possible to obtain smaller chitosan nanoparticles (<50 nm) that embed drug loaded Pluronic-123 micelles when their structure is modified by Sodiumdodecylsulfate.