Researcher: Ünal, Özlem
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Ünal, Özlem
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Publication Metadata only Nanoparticle based induction heating at low magnitudes of magnetic field strengths for breast cancer therapy(Elsevier, 2019) Zuvin, Merve; Koçak, Muhammed; Akkoç, Yunus; Kutlu, Özlem; Gözüaçık, Devrim; Koşar, Ali; N/A; Department of Chemistry; Department of Chemistry; Ünal, Özlem; Acar, Havva Funda Yağcı; PhD Student; Faculty Member; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902Magnetic hyperthermia has received much attention during the last decade due to its implementation in cancer treatment. Recently, functionalized superparamagnetic iron oxide nanoparticles (SPION) emerged as a strong alternative adjuvant treatment approach, which complements conventional methods such as chemotherapy. In this study, we demonstrate the anticancer effect of Poly(acrylic acid)-coated, anti-HER2-tagged SPIONs on breast cancer cells using a low magnetic field strength of 0.8 kAm(-1), which is significantly lower compared to the literature, with a frequency of 400 kHz. Specificity was achieved via anti-HER2 antibody attachment to nanoparticles. HER2-positive SKBR3 and MDA-MB-453 cell lines internalized the nanoparticles successfully. These nanoparticles, which were not toxic to these cell lines, led to a prominent decrease in cell proliferation and survival in MDA-MB-453 cells when subjected to hyperthermia. Therefore, the hyperthermia-targeted SPION approach could be developed as a potential cancer treatment approach against breast cancer and possible other cancer types.Publication Metadata only Free-standing N-doped reduced graphene oxide papers decorated with iron oxide nanoparticles: stable supercapacitor electrodes(Wiley-V C H Verlag Gmbh, 2019) N/A; Department of Chemistry; N/A; Department of Chemistry; Department of Chemistry; Department of Chemistry; Beyazay, Tuğçe; Öztuna, Feriha Eylül Saraç; Ünal, Özlem; Acar, Havva Funda Yağcı; Ünal, Uğur; Researcher; Researcher; PhD Student; Faculty Member; Faculty Member; College of Sciences; College of Sciences; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; N/A; 178902; 42079In this study, graphene oxide paper is obtained via vacuum-assisted filtration of graphene oxide solution to prepare self-standing electrodes for supercapacitors. Simultaneous reduction and N-doping of graphene oxide paper are performed by chemical reduction followed by thermal annealing. Influence of different reduction techniques on the electrochemical properties of the self-standing papers is investigated. N-doped reduced graphene oxide papers are decorated with iron oxide nanoparticles to increase the energy density of the material. Increasing the amount of iron oxide nanoparticles in the composite paper results in enhanced capacitance. In the galvanostatic charge-discharge measurements, iron oxide/N-doped reduced graphene oxide electrode exhibits specific capacitance of 203 F g(-1) at 0.5 mA cm(-2). This value is remarkable since the electrode has a high mass loading of 2 mg cm(-2), which shows that the electrode can be used for practical purposes. Moreover, these electrodes operate in a wide potential window (1.6 V) and exhibit 79 % capacitance retention at 10000 cycles.Publication Metadata only Layer-by-layer grown electrodes composed of cationic Fe 3 O 4 nanoparticles and graphene oxide nanosheets for electrochemical energy storage devices(Amer Chemical Soc, 2019) Erdem, Emre; Department of Chemistry; N/A; Department of Chemistry; Department of Chemistry; Department of Chemistry; Öztuna, Feriha Eylül Saraç; Ünal, Özlem; Acar, Havva Funda Yağcı; Ünal, Uğur; Researcher; PhD Student; Faculty Member; Faculty Member; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Sciences; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; 178902; 42079Ultrathin electrodes composed of layer-by-layer assembled (3-aminopropyl)trimethoxysilane functionalized iron oxide nanoparticles and graphene oxide nanosheets were prepared by a simple and low-cost dip coating method without using any binders or conductive additives. The thickness of the Fe3O4/GO films was simply altered with the number of dip coating cycles. Multilayered films were chemically reduced with hydrazine vapor in order to increase the electrical conductivity. Characterization of multilayer films was performed with scanning transmission electron microscopy, UV-vis spectroscopy, atomic force microscopy, quartz crystal microbalance, X-ray photoelectron spectroscopy, and electron paramagnetic resonance spectroscopy. We have performed cyclic voltammetry and electrochemical impedance spectroscopy for the evaluation of Fe3O4/GO multilayers as possible electrochemical capacitor electrodes. Reduced Fe3O4/GO films exhibit high specific capacitances (varying between 200 and 350 F g(-1) at 5 mV s(-1)), Outperforming the layer-by-layer assembled iron oxides/carbon derivatives (carbon nanotube, graphene).Publication Metadata only Preclinical characterization of a novel palladium complex as anticancer drug candidate(Wiley, 2016) Erim, S. Durmuş; İçsel, Ceyda; Yılmaz, Veysel Turan; Ulukaya, Engin; Şahin, Önder; N/A; Department of Chemistry; Department of Chemistry; Department of Chemistry; Ünal, Özlem; Khodadust, Rouhollah; Acar, Havva Funda Yağcı; PhD Student; Other; Faculty Member; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; 178902N/APublication Metadata only Discovery of an exceptionally strong luminescence of polyethyleneimine-superparamagnetic iron oxide nanoparticles(Wiley-V C H Verlag Gmbh, 2018) Erdem, Emre; Ow-Yang, Cleva W.; N/A; Department of Chemistry; Department of Chemistry; N/A; N/A; Department of Chemistry; Department of Chemistry; Ünal, Özlem; Yurtsever, İsmail Ersin; Khodadust, Rouhollah; Yağcı, Mustafa Barış; Durmuşoğlu, Emek Göksu; Acar, Havva Funda Yağcı; PhD Student; Faculty Member; Other; Researcher; N/A; Faculty Member; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; College of Sciences; N/A; 7129; N/A; N/A; N/A; 178902Polyethyleneimine (PEI) is rarely recognized as a luminescent polymer but is frequently used for the production of cationic nanoparticles and tagged with an organic fluorophore to be tracked optically. Herein, a strongly luminescent, branched PEI-superparamagnetic iron oxide nanoparticle (bPEI-SPION) without a traditional fluorophore is reported. A tremendous enhancement (1200 times) in the weak blue luminescence of bPEI is achieved only if it is adsorbed on a SPION during the synthesis of nanoparticles, which is improved further upon protonation, irreversibly. This is quite unexpected since SPIONs are strong absorbers in the visible region. All reaction parameters, different synthetic methods, as well as protonation are studied as independent factors to understand the origin of such enhancement. Detailed spectroscopic analysis and density functional theory calculations indicate that partial amine oxidation and Fe3+ reduction takes place during the synthesis, which significantly contributes to the luminescence enhancement. In addition, PEI-SPION exhibits excitation wavelength dependent emission and maintains its magnetic properties.Publication Metadata only Effect of varying magnetic fields on targeted gene delivery of nucleic acid-based molecules(Springer, 2015) Oral, Özlem; Cikim, Taha; Zuvin, Merve; Gözüaçık, Devrim; Koşar, Ali; N/A; Department of Chemistry; Department of Chemistry; Ünal, Özlem; Acar, Havva Funda Yağcı; PhD Student; Faculty Member; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902Several physical methods have been developed to introduce nucleic acid expression vectors into mammalian cells. Magnetic transfection (magnetofection) is one such transfection method, and it involves binding of nucleic acids such as DNA, RNA or siRNA to magnetic nanoparticles followed by subsequent exposure to external magnetic fields. However, the challenge between high efficiency of nucleic acid uptake by cells and toxicity was not totally resolved. Delivery of nucleic acids and their transport to the target cells require carefully designed and controlled systems. In this study, we introduced a novel magnetic system design providing varying magnet turn speeds and magnetic field directions. The system was tested in the magnetofection of human breast (MCF-7), prostate (DU-145, PC-3) and bladder (RT-4) cancer cell lines using green fluorescent protein DNA as a reporter. Polyethylenimine coated superparamagnetic iron oxide nanoparticles (SPIONs) were used as nucleic acid carriers. Adsorption of PEI on SPION improved the cytocompatibility dramatically. Application of external magnetic field increased intracellular uptake of nanoparticles and transfection efficiency without any additional cytotoxicity. We introduce our novel magnetism-based method as a promising tool for enhanced nucleic acid delivery into mammalian cells.Publication Open Access Magnetofection of green fluorescent protein encoding DNA-bearing polyethyleneimine-coated superparamagnetic iron oxide nanoparticles to human breast cancer cells(American Chemical Society (ACS), 2019) Zuvin, Merve; Koşar, Ali; Gözüaçık, Devrim; Kutlu, Özlem; Kaya, Veysel Oğulcan; Kuruoğlu, Efe; Department of Chemistry; Department of Chemistry; Acar, Havva Funda Yağcı; Ünal, Özlem; PhD Student; Graduate School of Sciences and Engineering; 178902; N/AGene therapy is a developing method for the treatment of various diseases. For this purpose, the search for nonviral methods has recently accelerated to avoid toxic effects. A strong alternative method is magnetofection, which involves the use of superparamagnetic iron oxide nanoparticles (SPIONs) with a proper organic coating and external magnetic field to enhance the localization of SPIONs at the target site. In this study, a new magnetic actuation system consisting of four rare-earth magnets on a rotary table was designed and manufactured to obtain improved magnetofection. As a model, green fluorescent protein DNA-bearing polyethyleneimine-coated SPIONs were used. Magnetofection was tested on MCF7 cells. The system reduced the transfection time (down to 1 h) of the standard polyethyleneimine transfection protocol. As a result, we showed that the system could be effectively used for gene transfer.Publication Open Access Theranostic potential of self-luminescent branched polyethyleneimine-coated superparamagnetic iron oxide nanoparticles(Beilstein-Institut, 2022) N/A; Khodadust, Rouhollah; Acar, Havva Funda Yağcı; Ünal, Özlem; PhD Student; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; N/A; 178902; N/APolyethylenimine (PEI), which is frequently used for polyplex formation and effective gene transfection, is rarely recognized as a luminescent polymer. Therefore, it is usually tagged with an organic fluorophore to be optically tracked. Recently, we developed branched PEI (bPEI) superparamagnetic iron oxide nanoparticles (SPION@bPEI) with blue luminescence 1200 times stronger than that of bPEI without a traditional fluorophore, due to partial PEI oxidation during the synthesis. Here, we demonstrate in vitro dye free optical imaging and successful gene transfection with luminescent SPION@bPEI, which was further modified for receptor mediated delivery of the cargo selectively to cancer cell lines overexpressing the epidermal growth factor receptor (EGFR). Proapoptotic polyinosinic-polycytidylic acid sodium (PIC) was delivered to HeLa cells with SPION@bPEI and caused a dramatic reduction in the cell viability at otherwise non-toxic nanoparticle concentrations, proving that bPEI coating is still an effective component for the delivery of an anionic cargo. Besides, a strong intracellular optical signal supports the optically traceable nature of these nanoparticles. SPION@bPEI nanoparticles were further conjugated with Erbitux (Erb), which is an anti-EGFR antibody for targeting EGFR-overexpressing cancer cell lines. SPION@bPEI-Erb was used for the delivery of a GFP plasmid wherein the transfection was confirmed by the luminescence of the expressed gene within the transfected cells. Poor GFP expression in MCF7, a slightly better expression in HeLa, and a significant enhancement in the transfection of HCT116 cells proved a selective uptake and hence the targeting ability of Erb-tagged nanoparticles. Altogether, this study proves luminescent, cationic, and small SPION@bPEI nanoparticles as strong candidates for imaging and gene therapy.Publication Open Access Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles(BioMed Central, 2020) Akkoç, Yunus; Koçak, Muhammed; Nalbat, Esra; Doğan-Ekici, Asiye Işın; N/A; Department of Chemistry; Department of Chemistry; Ünal, Özlem; Acar, Havva Funda Yağcı; Gözüaçık, Devrim; PhD Student; Faculty Member; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902; N/ANanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.