Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

Browse

Filters

2014 - 20195

Settings

Has files: YesSubject: search.filters.subject.Cytotoxicity

Search Results

Now showing 1 - 5 of 5
  • Master Thesis
    Development of Sub-Cellular Organelle Targeted Fluorescent Silica Nanoparticles
    (Izmir Institute of Technology, 2019) Yüksel, Almila; Özçelik, Serdar; Özçelik, Serdar
    Silica nanoparticles have been studied extensively in cellular applications due to their physicochemical properties. The surface of silica nanoparticles represent the key parameter in biological studies. Owing to their versatile surface chemistry, have ability to increase bioavailability and selectivity. Therefore, it is significant to understand how biomolecules interact with the surface of silica nanoparticles. The study reviews how synthesized both negative and positive potential silica nanoparticles and can transfer their properties to the cells. In the second part, our synthesized silica nanoparticles were characterized physicochemically using some instrumental devices. To answer the role of silica nanoparticles in the cells, some outcomes such as viability test, image analysis, colocalization analysis and mitochondrial membrane potential were investigated. A549 (adenocarcinomic human alveolar basal epithelial cells) and BEAS-2B (human bronchial epithelial cells) cell lines were selected in our studies. Our results showed the cytotoxicity was dose and time dependent in direct proportion. Mitochondrial accumulation were observed in cells treated with the silica nanoparticles according to Pearson’s Coefficient Correlation and Image J analysis. The study concluded that the silica nanoparticles can be used in the field of targeted delivery and bioimaging in cellular studies.
  • Master Thesis
    Naphthoquinones From Natural Sources and Their Bioactivities
    (Izmir Institute of Technology, 2019) Kul, Demet; Bedir, Erdal
    Onosma L. is a large heterogenic genus of Boraginaceae family includes about 230 species distributed mainly in Central Asia and the Mediterranean region. According to ‘Flora of Turkey, Onosma genus is represented with 104 species and 108 taxa and 52% of which are endemic. Phytochemical studies have revealed that Onosma species possess various constituents including alkaloids, naphthoquinones, polyphenols, phytosterols, terpenoids and fatty acids. Naphthoquinones are naturally widespread secondary metabolites deriving from some higher plants, fungi and bacteria, and have shown significant biological activities such as cytotoxic, antibacterial, antifungal and wound healing. In this thesis, bioassay-guided isolation studies were performed on Onosma aksoyii and Onosma isaurica to obtain naphthoquinone type cytotoxic compounds and investigate their topoisomerase inhibitory properties. Isolation studies were guided by MTT assay using three human cancer cell lines (HeLa, HCC-1937, DU-145) and a nontumor cell line (MRC-5). whereas the enzyme inhibition tests were against human topoisomerases IIα and IIβ. Six compounds, one of which was new (OA-PE-D1), were isolated using chromatographic methods and their structures were elucidated by spectral methods (1D, 2D NMR, and MS). The known compounds were acetylshikonin, β,β- dimethylacrylshikonin, arnebidin, arnebifuranone and shikonofuran E. The cytotoxicity screenings showed that these compounds had IC50 values ranging from 6.485 μM to 32 μM. According to topoisomerase inhibition studies, OA-PE-D1 and β,β- dimethylacrylshikonin showed promising inhibitory effects on topoisomerase IIβ at dose of 1 mg/mL.
  • Master Thesis
    Development of Endosome Disruptive Peptide and Peg Conjugate Based Doxorubicin Delivery System
    (Izmir Institute of Technology, 2019) Özkıyıcı, Selin; Top, Ayben
    In this study, it was aimed to develop a drug carrier system including a TAT-derived cell penetrating peptide in order to provide fast transport of anticancer drugs from endosomal compartments to nucleus. The drug delivery system, denoted as mPEGpeptide- oxime-DOX, was based on polyethylene glycol, endosome disruptive peptide (G2RQR3QR3G2S), and doxorubicin (DOX) conjugate. Control drug delivery system, lack of the peptide (mPEG-oxime-DOX) was also synthesized to assess the effect of the peptide on the physiochemical and drug release properties of the drug carrier. As the first synthesis step, mPEG-OH was converted to mPEG-aldehyde form using DMSO-acetic anhydride oxidation reaction and aldehyde functionalization was determined by using FTIR and NMR spectroscopy. The peptide and mPEG-peptide were synthesized using solid phase synthesis protocol, and their purities were confirmed using HPLC and MALDI-TOF mass spectroscopy analyses. Prior to DOX conjugation, hydroxyl group of serine residue in the mPEG-peptide system was oxidized to aldehyde. The anticancer drug was attached to the carrier molecules via amine-aldehyde reaction forming an acid cleavable oxime bond. Drug release, size distribution, and stability of the PEG-peptideoxime- DOX system were evaluated and compared with those results of the control drug delivery system. For mPEG-oxime-DOX, a pH programmed DOX release with the respective % DOX release values of ~68 % and ~28 % at pH 5.0 and pH 7.4 was observed. For mPEG-peptide-oxime-DOX, on the other hand, quite low DOX release (~10-15 %) was obtained for both pH values suggesting possible interaction between DOX and the peptide. Mean size value of the mPEG-oxime-DOX was measured as ~24 nm. However, mPEG-peptide-oxime-DOX, had quite lower hydrodynamic diameter values (~3nm and ~6 nm at pH 5.0 and pH 7.4, respectively) possibly due to repulsions between the arginines in the peptide domain. Observation of the morphology and evaluation of the cytotoxicity of these drug delivery systems are underway.
  • Master Thesis
    Development of Peg and Peg-Peptide Based Drug Delivery Systems
    (Izmir Institute of Technology, 2016) Balcı, Beste; Top, Ayben
    In this study, two types of drug delivery systems (DDS) were prepared; mPEG (methoxy polyethylene glycol)-HYD (hydrazide)-DOX and mPEG-peptide-(HYD)-DOX. In the design of the conjugates, mPEG was used to increase the blood circulation time. HYD provided an acid cleavable bond between the carrier molecule and DOX, whereas peptide containing histidines imparted pH responsiveness of the molecule. Doxorubicin (DOX) was selected as a model anti-cancer drug. DDS were synthesized using two steps; hydrazide functionalization of carboxylic acid of the carrier molecule followed by DOX conjugation. Hydrazide form of the carrier molecules denoted as HYD1 and HYD2 were obtained using adipic acid dihydrazide (AADH) and carbohydrazide (CH), respectively. To increase DOX conjugation, trifluoroacetic acid (TFA) and DOX amounts were changed and the reactions were carried out at the conditions giving the highest DOX conjugation (mPEG-HYD:DOX:TFA= 2.5mg:2mg:20μL per 1 mL of DMSO). The peptide (AT1=CGGGHHHHHHGGGE) was synthesized using solid phase peptide synthesis (SPPS) and PEGylated using mPEG-maleimide to obtain mPEG-AT1 conjugate. The purity of AT1 and mPEG-AT1 were confirmed using mass spectroscopy and high performance liquid chromatography (HPLC). DOX conjugation percentages were obtained as 62  7, 60  3 and 35 + 3 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-HYD1-DOX, respectively. Drug release studies indicated modest pH responsiveness of the carrier molecules obtained using AADH. On the other hand, mPEG-HYD2-DOX released  13% of drug at the end of the 72h independent of pH. For mPEG-AT1-DOX, drug release percentage values were obtained as  15% and  30% at pH 7.4 and 5.0 respectively. Cytotoxicity of the conjugates of DDS was determined using lung cancer (A-549) cell lines. DOX equivalent IC50 values were determined as 20, 40 and 5 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-DOX respectively.
  • Master Thesis
    Investigation of Biocompatibility of Calcium Phosphate Based Materials and Cements
    (Izmir Institute of Technology, 2014) Karataş, Özlem; Çiftçioğlu, Muhsin; Harsa, Hayriye Şebnem
    Calcium phosphate cements (CPCs) have been extensively investigated due to their excellent biocompatibility, osteoconductivity, potential resorbability in dentistry and orthopedics. They have numerous advantages over other calcium phosphate-based materials. The CPC precursor powders were prepared in the initial stage of this work. Tetracalcium phosphate (TTCP) powders coded as TTCP-1 (obtained from H3PO4 and CaCO3) and TTCP-2 (obtained from NH4H2PO4 and CaCO3) were prepared by heat treatment of the calcium and phosphate source mixtures at 1350°C. Brushite powders were produced by aqueous chemical methods. A series of CPCs (HA cements) were prepared by using the TTCP-1 and brushite powders which were mixed with 0.2 M and 0.3 M phosphate buffer solutions at three different solid/liquid ratios (2.4, 2.7 and 3.2 g/ml) with three different HA initial seed contents (3%, 1.5% and 0.0 wt% ). The setting times of CPCs were determined to be in the 3.5-24 minute range. The phase structure and surface morphology of the cements and precursor powders were characterized by XRD and SEM. XRD analysis of powders revealed the presence of the characteristic TTCP and brushite peaks. XRD analysis also indicated that all cement samples were composed by HA phase with different crystallinity and other phases were not detected. Rod and plate-like hydroxyapatite crystals were observed in the SEM micrographs of all CPCs. Cytotoxicity testing was performed using the MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay to determine the number of viable cells in the presence of powders and HA cements. Cytotoxicity results indicated that brushite powder caused sharp decreases in cell viability at the end of 24, 48 and 72 hours at all powder extract concentrations. TTCP-1 and TTCP-2 powders unlike brushite had no toxic effect with cell viability values over 74 %. Almost all CPCs prepared in this work had no cytotoxic effects.