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Öğe Application of Centri-voltammetry to Cytosensors: Cyto-centrivoltammetry(Pergamon-Elsevier Science Ltd, 2016) Tepeli, Yudum; Barlas, Firat Baris; Timur, Suna; Anik, UlkuIn this work, a centri-voltammetric cytosensor suitable for the for detection of folate receptor positive cervical cancer (HeLa) cells was developed for the first time. In order to see the effect of centrifugation, developed cytosensor's performance was compared in terms of analytical characteristics values, in the presence and absence of centri-voltammetry. As a result, in the absence of centri-voltammetry, the linear range was found between 75 cells/mL and 10(6) cells/mL with limit of detection (LOD) value as 75 cells/mL and with R.S.D value of 3.5% (for 5.0 x 10(4) HeLa cells/mL (n = 3)). Meanwhile in the presence of centri-voltammetry, the linear range was found between 8.0 cells/mL and 5 x 10(6) cells/mL and LOD value was calculated as 8 cells/mL with R.S.D value of 4.7% for the same concentration. (C) 2016 Elsevier Ltd. All rights reserved.Öğe Bioconjugation and Applications of Amino Functional Fluorescence Polymers(Wiley-V C H Verlag Gmbh, 2017) Geyik, Caner; Guler, Emine; Gumus, Zinar Pinar; Barlas, Firat Baris; Akbulut, Huseyin; Demirkol, Dilek Odaci; Timur, Suna; Yagci, YusufSynthesis and novel applications of biofunctional polymers for diagnosis and therapy are promising area involving various research domains. Herein, three fluorescent polymers, poly(p-phenylene-co-thiophene), poly(p-phenylene), and polythiophene with amino groups (PPT-NH2, PPP-NH2, and PT-NH2, respectively) are synthesized and investigated for cancer cell targeted imaging, drug delivery, and radiotherapy. Polymers are conjugated to anti-HER2 antibody for targeted imaging studies in nontoxic concentrations. Three cell lines (A549, Vero, and HeLa) with different expression levels of HER2 are used. In a model of HER2 expressing cell line (A549), radiotherapy experiments are carried out and results show that all three polymers increase the efficacy of radiotherapy. This effect is even more increased when conjugated to anti-HER2. In the second part of this work, one of the selected polymers (PT-NH2) is conjugated with a drug model; methotrexate via pH responsive hydrazone linkage and a drug carrier property of PT-NH2 is demonstrated on neuroblastoma (SH-SY5Y) cell model. Our results indicate that, PPT-NH2, PPP-NH2, and PT-NH2 have a great potential as biomaterials for various bioapplications in cancer research.Öğe Caffeic acid phenethyl ester protects lung alveolar epithelial cells from cigarette smoke-induced damage(Tubitak Scientific & Technical Research Council Turkey, 2015) Barlas, Firat Baris; Erdogan, SuatBackground/aim: To evaluate the influence of caffeic acid phenethyl ester (CAPE) on cigarette smoke (CS)-induced cell damage, oxidative stress, and inflammation in human alveolar epithelial cells. Materials and methods: A549 alveolar epithelial cells were divided into control, CS exposure, CAPE, and CS+CAPE treatment groups. Undiluted CS-exposed medium (100%) and three dilutions (50%, 25%, and 10%) of CS-exposed media were applied to cultured A549 cells, which were analyzed after 3 h of incubation. Viability was measured by MTT assay, the gene expressions were evaluated by real-time PCR, and spectrophotometric techniques were used for biochemical assessments. Results: While CS exposure markedly reduced cellular viability by 32% after 3 h of incubation, 2.5 mu M CAPE treatments prevented CS-induced cell death by 40% in the cells. CS exposure triggered lipid peroxidation and depleted antioxidant capacity through inhibiting catalase activity and depleting glutathione levels. Moreover, CS increased nitric oxide production via upregulation of iNOS expression. CAPE treatment significantly restored antioxidant capacity and prevented lipid peroxidation. Cigarette smoke exposure induced inflammation by significantly upregulating TNF-alpha, IL-1 beta, and COX-2 mRNA expressions (3-, 2- and 25-fold, respectively). CAPE treatment of A549 cells significantly reversed the inflammation. Conclusion: CAPE may potentially represent a new therapeutic option in the prevention of CS-induced lung damages.Öğe The cell-penetrating YopM protein-functionalized quantum dot-plasmid DNA conjugate as a novel gene delivery vector(Academic Press Inc Elsevier Science, 2020) Ugurlu, Ozge; Barlas, Firat Baris; Evran, Serap; Timur, SunaNon-viral gene delivery systems have great potential for safe and efficient gene therapy, while inefficient cellular and nuclear uptake remain as the major hurdles. Novel approaches are needed to enhance the transfection efficiency of non-viral vectors. in accordance with this need, the objective of this study was to construct a nonviral vector that could achieve gene delivery without using additional lipid-based transfection agent. We aimed to impart self-delivery property to a non-viral vector by using the cell and nucleus penetrating properties of YopM proteins from the three Yersinia spp. (Y. pestis, Y. enterocolotica and Y. pseudotuberculosis). Plasmid DNA (pDNA) encoding green fluorescent protein (GFP) was labeled with quantum dots (QDs) via peptide-nucleic acid (PNA) recognition site. Recombinant YopM protein was then attached to the conjugate via a second PNA recognition site. the YopM- QDs- pDNA conjugate was transfected into HeLa cells without using additional transfection reagent. All three conjugates produced GFP fluorescence, indicating that the plasmid was successfully delivered to the nucleus. As control, naked pDNA was transfected into the cells by using a commercial transfection reagent. the Y. pseudotuberculosis YopM-functionalized conjugate achieved the highest GFP expression, compared to other two YopM proteins and the transfection reagent. To the best of our knowledge, YopM protein was used for the first time in a non-viral gene delivery vector.Öğe Enhancing chemotherapeutic efficacy: Niosome-encapsulated Dox-Cis with MUC-1 aptamer(Wiley, 2024) Barlas, Firat Baris; Olceroglu, Bilge; Seleci, Didem Ag; Gumus, Zinar Pinar; Siyah, Pinar; Dabbek, Meriam; Garnweitne, GeorgBackground: Cancer remains a formidable global health challenge, currently affecting nearly 20 million individuals worldwide. Due to the absence of universally effective treatments, ongoing research explores diverse strategies to combat this disease. Recent efforts have concentrated on developing combined drug regimens and targeted therapeutic approaches. Objective: This study aimed to investigate the anticancer efficacy of a conjugated drug system, consisting of doxorubicin and cisplatin (Dox-Cis), encapsulated within niosomes and modified with MUC-1 aptamers to enhance biocompatibility and target specific cancer cells. Methods: The chemical structure of the Dox-Cis conjugate was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-Q-TOF/MS). The zeta potential and morphological parameters of the niosomal vesicles were determined through Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). In vitro assessments of cell viability and apoptosis were conducted on MUC-1 positive HeLa cells and MUC-1 negative U87 cells. Results: The findings confirmed the successful conjugation of Dox and Cis within the niosomes. The Nio/Dox-Cis/MUC-1 formulation demonstrated enhanced efficacy compared to the individual drugs and their unencapsulated combination in both cell lines. Notably, the Nio/Dox-Cis/MUC-1 formulation exhibited greater effectiveness on HeLa cells (38.503 +/- 1.407) than on U87 cells (46.653 +/- 1.297). Conclusion: The study underscores the potential of the Dox-Cis conjugate as a promising strategy for cancer treatment, particularly through platforms that facilitate targeted drug delivery to cancer cells. This targeted approach could lead to more effective and personalized cancer therapies.Öğe Folic-Acid-Modified Conducting Polymer: Electrochemical Detection of the Cell Attachment(Wiley-V C H Verlag Gmbh, 2016) Azak, Hacer; Barlas, Firat Baris; Yildiz, Huseyin Bekir; Gulec, Kadri; Demir, Bilal; Demirkol, Dilek Odaci; Timur, SunaHere, postfunctionalization and bioapplication of a pi-conjugated polymer named 4-[4H-dithieno(3,2-b:2',3'-d)pyrrol-4-yl]aniline (DTP-aryl-NH2) are reported, which is successfully synthesized via electropolymerization onto the glassy carbon electrode. Folic acid (FA) is used to modify the amino functional polymer via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide chemistry for the further steps. The selective adhesion of folate receptor positive cells on the surface is followed by the electrochemical methods. Cyclic voltammetry and electrochemical impedance spectroscopy have been used to characterize stepwise modification of the electroactive surface. After optimization studies such as scan rate during the polymer deposition, FA amount for the efficient surface targeting, incubation time with the cells etc., analytical characterization is carried out. The surface morphologies at each step are imaged by using fluorescence microscopy.Öğe A Novel DAD Type and Folic Acid Conjugated Fluorescent Monomer as a Targeting Probe for Imaging of Folate Receptor Overexpressed Cells(Wiley-Blackwell, 2014) Kanik, Fulya Ekiz; Ag, Didem; Seleci, Muharrem; Barlas, Firat Baris; Kesik, Melis; Hizalan, Gonul; Akpinar, Hava; Timur, Suna; Toppare, LeventWe describe a modification and post-functionalization technique for a donor-acceptor-donor type monomer; 6-(4,7-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2H-benzo[d][1,2,3]triazol-2-yl)hexan-1-amine. Folic acid was attached to the fluorescent structure. The conjugation was confirmed via NMR and Fourier transform infrared analyses. Cytotoxicity was investigated and the comparison of association of targeted monomeric structures in tumor cells was monitored via fluorescence microscopy. (C) 2014 American Institute of Chemical EngineersÖğe Novel glyconanoconjugates: synthesis, characterization and bioapplications(Royal Soc Chemistry, 2016) Telli, Fatma Cetin; Demir, Bilal; Barlas, Firat Baris; Guler, Emine; Timur, Suna; Salman, YesimThe impressive properties of nanoparticles (NPs) have caused them to gain considerable attention for biological applications such as cancer therapy. Among the many nanoparticles used in the treatment of cancer, carbohydrate derivatized modified NPs lead the way with enhanced internalization and therapy efficacy for cancerous cell lines. In this research, an aminochlorase Schiff base, which can be beneficial as a therapy material, with a galactose residue was used as a potentially active modifier. Gold and silver nanoparticles (AuNPs and AgNPs) can be readily modified with a sugar Schiff base ligand (1) by using cysteamine hydrochloride residues as a linker between the nanoparticle surface and the ligand. The resulting glyco-nanoparticles were characterized using transmission electron microscopy, X-ray photoelectron microscopy and spectrophotometric techniques. Additionally, this modification type within a galactose derived Schiff base is the first work with a bioapplication, especially in radiotherapy. For further biological applications in cancerous cell lines, two commonly used cell lines, human cervix adenocarcinoma (HeLa) and human lung carcinoma cell line (A549) were introduced into the biological evaluation of those NP-ligand conjugates and satisfactory radioactivity results were obtained because of the radiosensitizing effect of the AuNPs and AgNPs.Öğe One-Pot Photo-Induced Sequential CuAAC and Thiol-Ene Click Strategy for Bioactive Macromolecular Synthesis(Amer Chemical Soc, 2014) Doran, Sean; Murtezi, Eljesa; Barlas, Firat Baris; Timur, Suna; Yagci, YusufConceptually new one-pot photoinduced sequential click reactions were implemented to yield novel block copolymers with the ability for cell adhesion. Poly(epsilon-caprolcatone) possessing clickable functional groups at the chain ends, namely alpha-alkynyl-omega-alkenyl-poly(epsilon-caprolactone) (A-PCL-MA), was prepared by ring-opening polymerization of epsilon-caprolactone using propargyl alcohol in the presence of stannous octoate at 110 degrees C followed by esterification with methacrylic acid. Azide-functional poly(methyl methacrylate) (PMMA-N-3) was prepared independently by atom transfer radical polymerization (ATRP) followed by an azidation process using sodium azide. Finally, A-PCL-MA was reacted with PMMA-N-3 and N-acetyl-L-cysteine (NAC) in a one-pot process through photoinduced sequential click reactions to furnish desired bioactive block copolymer (PMMA-b-PCL-NAC). A matrix for cell adhesion was then prepared from the yielded block copolymer PMMA-b-PCL-NAC and cell proliferation on the matrix was measured. Cells from the Vero cell line (African green monkey kidney epithelial) were incubated on the matrix, and after 48 h, they showed greater cell proliferation than the commercially available cell culture plates used as comparison.Öğe Poly(p-phenylene) with Poly(ethylene glycol) Chains and Amino Groups as a Functional Platform for Controlled Drug Release and Radiotherapy(Wiley-V C H Verlag Gmbh, 2016) Guler, Bahar; Akbulut, Huseyin; Barlas, Firat Baris; Geyik, Caner; Demirkol, Dilek Odaci; Senisik, Ahmet Murat; Arican, Halil Armagan; Coskunol, Hakan; Timur, Suna; Yagci, YusufConventional cancer treatments such as chemotherapy, radiotherapy, or combination of these two result in side effects, which lower the quality of life of the patients. To overcome problems with these methods, altering the drug properties by conjugating them to carrier polymers has emerged. Such polymeric carriers also hold the potential to make tumor cells more sensitive to radiation therapy. Herein, poly(p-phenylene) (PPP) polymer with poly(ethylene glycol) (PEG) chains and primary amino groups (PPP-NH2-g-PEG) is synthesized and conjugated with anticancer drug Doxorubicin (DOX). pH dependent drug release experiments are performed at pH 5.3 and pH 7.4, respectively. Cell viability studies on human cervix adenocarcinoma cells show that lower doses of DOX inhibit cell proliferation when conjugated with nontoxic doses of PPP-NH2-g-PEG polymer. Additionally, PPP-NH2-g-PEG/Cys/DOX bioconjugate significantly increases radiosensitive properties of DOX. It is possible to use lower doses of DOX when conjugated to PPP-NH2-g-PEG in combination with radiotherapy.Öğe Polymeric Thioxanthones as Potential Anticancer and Radiotherapy Agents(Wiley-V C H Verlag Gmbh, 2016) Yilmaz, Gorkem; Guler, Emine; Barlas, Firat Baris; Timur, Suna; Yagci, YusufThioxanthone (TX) and its derivatives, which are widely used as photoinitiators in UV curing technology, hold promising research interest in biological applications. In particular, the use of TXs as anticancer agent has recently been manifested as an outstanding additional property of this class of molecules. Incorporation of TX molecules into specially designed polymers widens their practical use in such applications. In this study, two water-soluble, biocompatible, and stable polymers, namely poly(vinyl alcohol) and poly(ethylene glycol), possessing TX moieties at the side chains and chain ends, respectively, are prepared and used as anticancer and radiotherapy agents. The findings confirm that both polymers are potential candidates for therapeutic agents as they possess useful features including water-solubility, radiosensitizer effect, and anticancer activity in a polymeric scaffold.Öğe Synthesis, characterization and biological application of dinuclear Cu(II) complexes of Schiff base ligands of galactochloralose and alpha-chloralose(Elsevier Science Sa, 2018) Salman, Yesim; Barlas, Firat Baris; Yavuz, Murat; Kaya, Kerem; Timur, Suna; Telli, Fatma CetinFour novel dinuclear Cu(II) complexes (1a-4a) have been prepared from ONO-tridentate chiral Schiff base derivatives of chloralose (1-4). All the new complexes (1a-4a) have been characterized by Fourier transform infrared spectroscopy, UV-visible spectroscopy and elemental analysis. The complex 2a was further characterized by X-Ray crystallography. And also, the magnetic susceptibility measurement of this complex (2a, mu(eff) 2.61 BM/dimer) was measured at room temperature. The activities of ONO-tridentate chiral Schiff base derivatives of chloralose (1-4) and their dinuclear Cu(II) complexes (1a-4a) on viability of human cervical cancer cell line (HeLa) were investigated by MIT assay. The obtained results indicated that the Schiff base ligand 1 and its dinuclear Cu(II) complex (1a) have excellent cytotoxic activity. Also, dinuclear Cu(II) complexes of the galactochloralose and alpha-chloralose derivative Schiff base ligands were screened for their in vitro antimicrobial activity against eight bacterial species as well as yeast species Candida albicans ATCC 10231 using disc diffusion method. Complex 4a exhibited promising in vitro antimicrobial activity with inhibition zone diameter from 10 to 22 mm against the tested Gram-positive bacterial strains and yeast C. albicans.Öğe Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma(Mdpi, 2021) Ag Seleci, Didem; Maurer, Viktor; Barlas, Firat Baris; Porsiel, Julian Cedric; Temel, Bilal; Ceylan, Elcin; Timur, SunaThe development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.
