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Öğe A comparative study of receptor-targeted magnetosome and HSA-coated iron oxide nanoparticles as MRI contrast-enhancing agent in animal cancer model(Humana Press, 2018) Erdal, Ebru; Demirbilek, Murat; Yeh, Yasan; Akbal, Öznur; Ruff, Laura; Bozkurt, Damla; Çabuk, Ahmet; Senel, Yasin; Gümüşkaya, Berrak; Algın, Oktay; Çolak, Şeyda; Esener, Sadık; Denkbaş, Emir BakiMagnetosomes are specialized organelles arranged in intracellular chains in magnetotactic bacteria. The superparamagnetic property of these magnetite crystals provides potential applications as contrast-enhancing agents for magnetic resonance imaging. In this study, we compared two different nanoparticles that are bacterial magnetosome and HSA-coated iron oxide nanoparticles for targeting breast cancer. Both magnetosomes and HSA-coated iron oxide nanoparticles were chemically conjugated to fluorescent-labeled anti-EGFR antibodies. Antibody-conjugated nanoparticles were able to bind the MDA-MB-231 cell line, as assessed by flow cytometry. To compare the cytotoxic effect of nanoparticles, MTT assay was used, and according to the results, HSA-coated iron oxide nanoparticles were less cytotoxic to breast cancer cells than magnetosomes. Magnetosomes were bound with higher rate to breast cancer cells than HSA-coated iron oxide nanoparticles. While 250 mu g/ml of magnetosomes was bound 92 +/- 0.2%, 250 mu g/ml of HSA-coated iron oxide nanoparticles was bound with a rate of 65 +/- 5%. In vivo efficiencies of these nanoparticles on breast cancer generated in nude mice were assessed by MRI imaging. Anti-EGFR-modified nanoparticles provide higher resolution images than unmodified nanoparticles. Also, magnetosome with anti-EGFR produced darker image of the tumor tissue in T2-weighted MRI than HSA-coated iron oxide nanoparticles with anti-EGFR. In vivo MR imaging in a mouse breast cancer model shows effective intratumoral distribution of both nanoparticles in the tumor tissue. However, magnetosome demonstrated higher distribution than HSA-coated iron oxide nanoparticles according to fluorescence microscopy evaluation. According to the results of in vitro and in vivo study results, magnetosomes are promising for targeting and therapy applications of the breast cancer cells.Öğe Aligned bacterial PHBV nanofibrous conduit for peripheral nerve regeneration(Taylor & Francis Ltd, 2015) Demirbilek, Murat; Sakar, Mustafa; Karahaliloğlu, Zeynep; Erdal, Ebru; Yalçın, Eda; Bozkurt, Gökhan; Korkusuz, Petek; Bilgiç, Elif; Temuçin, Çağri Mesut; Denkbaş, Emir BakiThe conventional method of peripheral nerve gap treatment is autografting. This method is limited. In this study, an aligned nanofibrous graft was formed using microbial polyester, Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The regenerative effect of the graft was compared with that of autografting in vivo. To determine the regenerative effect, rats were assessed with sciatic nerve functional index, electromyographic evaluation, and histological evaluation. Results found in this study include PHBV grafts stimulated progressive nerve regeneration, although regeneration was not comparable with that of autografting. We conclude that the study results were promising for aligned bacterial polymeric grafts for peripheral nerve regeneration.Öğe Antibacterial agent loaded fungal polymer for use as a wound dressing(Hacettepe Üniversitesi, 2011) Güven, Eylem; Şam, Mesut; Erdal, Ebru; Karahaliloğlu, Zeynep; Candan, Dilek; Sağlam, Necdet; Denkbaş, Emir BakiThis study is mainly concerned with the preparation and characterization of a novel wound dressing, in the form of three-dimensional micro-porous structure, from extracellular polysaccharide produced by Trametes Versicolor, a white-rot basidiomycete. A model antibiotic (i.e., ciprofloxacin) was loaded into these wound dressings in the preparation procedure. The prepared wound dressings were investigated and evaluated in four main sections. In the first part, morphological evaluations were made by using scanning electron microscopy and the obtained images revealed that the wound dressings were having highly porous structure with interconnected pores. Antibacterial agent loaded-wound dressings were also investigated with swelling behavior, in vitro drug release and biodegradation studies. Obtained results showed that wound dressings from fungal polymer including antibacterial agent could provide great potential in the treatment of dermal wounds as a new kind of wound dressing material.Öğe Antisense oligonucleotide delivery to cancer cell lines for the treatment of different cancer types(Taylor & Francis Ltd, 2016) Kılıçay, Ebru; Erdal, Ebru; Hazer, Baki; Türk, Mustafa; Denkbaş, Emir BakiAmphiphilic poly(3-hydroxylalkanoate) (PHA) copolymers find interesting applications in drug delivery. The aim of this study was to prepare nucleic acid adsorbed on (PHB-b-PEG-NH2) nanoparticle platform for gene delivery. For this purpose, PHB-b-PEG-NH2 block copolymers were synthesized via transesterification reactions. The copolymers obtained were characterized by Proton Nuclear Magnetic Resonance (H-1-NMR), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) techniques. The cytotoxic, apoptotic and necrotic effects of these nanoparticles in the MDA 231 human breast cancer cell, the A549 human lung cancer cell and the L929 fibroblast cell lines were also investigated.Öğe Comparison of protein- and polysaccharide-based nanoparticles for cancer therapy: synthesis, characterization, drug release, and interaction with a breast cancer cell line(Taylor & Francis, 2017) Akbal, Öznur; Erdal, Ebru; Vural, Tayfun; Kavaz, Do?a; Denkbaş, Emir BakiIn this study, human serum albumin (HSA) was used as a protein-based material and poly (3-hydroxybutyrate) (PHB)-carboxymethyl chitosan (CMCh) as a polysaccharide-based material for the production of nanoparticles to be used as nanocarriers in cancer therapy. HSA and PHB-CMCh nanoparticles were prepared and characterized with a Zeta Sizer, Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscope. The effects of the pH value of the suspending medium and the amounts of crosslinker and polymer concentration on nanoparticle size and size distribution were investigated. The anticancer-agent etoposide was used as a model drug and encapsulated in nanoparticles to obtain drug release profiles. The entrapment efficiency of HSA nanoparticles was found to be greater than that of PHB-CMCh nanoparticles. To achieve "active'' targeting of cancer cells, the nanoparticles were modified with concanavalin A. In the final step of the study, the interaction of nanoparticles with cancer cells was investigated in cytotoxicity and cellular uptake studies.Öğe Oxidative stress parameters of L929 cells cultured on plasma-modified PDLLA scaffolds(Humana Press, 2011) Demirbilek, Melike Erol; Demirbilek, Murat; Karahaliloğlu, Zeynep; Erdal, Ebru; Vural, Tayfun; Yalçın, Eda; Sağlam, Necdet; Denkbaş, Emir BakiOxidative stress may produce high level of reactive oxygen species (ROS) following cell exposure to endogenous and exogenous factors. Recent experiments implicate oxidative stress as playing an essential role in cytotoxicity of many materials. The aim of this study was to measure intracellular malondialdehyde (MDA), advanced oxidation protein product (AOPP) levels, and superoxide dismutase (SOD) activities of L929 fibroblasts cultured on PDLLA, polyethylene glycol (PEG), or ethylenediamine (EDA) grafted PDLLA by plasma polymerization method. Cell proliferation on these scaffolds was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The study showed that MDA, AOPP levels, and SOD activities in L929 fibroblast cells cultured on all scaffolds were significantly different compared to the control group and each other. The highest MDA (0.42 +/- 0.76 nmol/mg protein), AOPP (14.99 +/- 4.67 nmol/mg protein) levels, and SOD activities (7.49 +/- 3.74 U/mg protein) were observed in cells cultured on non-modified scaffolds; meanwhile, the most cell proliferation was obtained in EDA-modified scaffolds (MDA 0.15 +/- 0.14 nmol/mg protein, AOPP 13.12 +/- 3.86 nmol/mg protein, SOD 4.82 +/- 2.64 U/mg protein). According to our finding, EDA- or PEG-modified scaffolds are potentially useful as suitable biomaterials in tissue engineering.Öğe Preparation and characterization of magnetically responsive bacterial polyester based nanospheres for cancer therapy(Amer Scientific Publishers, 2012) Erdal, Ebru; Kavaz, Doğa; Şam, Mesut; Demirbilek, Murat; Demirbilek, Melike Erol; Sağlam, Necdet; Denkbaş, Emir BakiPolyhydroxyalkanoates (PHA) are natural, thermoplastic polyesters and due to their biocompatible and biodegradable properties they are good alternatives for the production of scaffolds for engineered tissues or nanoparticles for drug delivery. As a member of polyhydroxyalkanoate family, polyhydroxybutyrates (PHB) have been widely used as a biomaterial for in vitro and in vivo studies since their mechanical properties are very similar to conventional plastics. By using multi-emulsion technique, iron oxide particles were coated with polyhydroxybutyrate (PHB) polymer synthesized from Alcaligenes eutrophus bacteria and the magnetic carrier system was prepared accordingly. The bare nanoparticles and magnetic nanoparticles were morphologically, structurally and magnetically characterized by using Scanning electron microscope (SEM) and Atomic force microscope (AFM); Fourier Transform Infrared Spectrometry (FTIR), and Electron Spin Resonance (ESR) and Vibrating Sample Magnetometer (VSM) techniques, respectively. Particle size of PHB nanoparticles was determined by Zeta Sizer. It was found that the smallest particles were in the range of 239,43+/-5,25 nm in diameter. Concanavalin-A (Con-A) was used for targeting the Cancer cells while etoposide was used as drug. Con-A and etoposide were loaded onto the particles. Release studies of etoposide were evaluated and the system was optimized for the further in vivo applications. Finally different formulation magnetic PHB nanoparticles cytotoxicity were evaluated in cell culture studies and used He La cell line (cervical cancer cells) as a cancer cells and L929 cells (mouse fibroblast cells) as a non-cancer cell line.Öğe Preparation and characterization of polyhydroxybutyrate scaffolds to be used in tissue engineering applications(Hacettepe Üniversitesi, 2008) Güven, Öztürk Eylem; Demirbilek, Murat; Sağlam, Necdet; Karahaliloğlu, Zeynep; Erdal, Ebru; Bayram, Cem; Denkbaş, Emir BakiPolyhydroxyalkanoates (PHA) are good alternatives on account of biocompatible and biodegradable properties to produce materials as scaffolds for engineered tissues. Polyhydroxybutyrate (PHB) which is a member of polyhydroxyalkanoate family have been widely used as a biomaterial for in vitro and in vivo studies due to its unique properties such as improved flexibility and processability. In this study polyhydroxybutyrate scaffolds were prepared for tissue engineering applications. In order to improve cell attachment on the scaffolds they were modified. During the modification three different immunologically inactive compounds, polyetyhylene glycol (PEG), 2-hydroxyethyl methacrylate (HEMA) and ethylenediamine (EDA) were used in radio frequency glow discharge (RFGD) plasma polymerization system. Morphological evaluations were obtained by using scanning electron microscopy. Obtained results showed high and interconnected porosity. In vitro weight loss profiles of the scaffolds were investigated by using gravimetric method and found to be influenced by PHB concentration used in the preparation of scaffolds. Their biological promotion of activities including cell attachment, morphology and proliferation on L929 mouse fibroblast cells were examined and cytotoxicity tests were performed at the last part of the study.