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    Bisphosphonate-functionalized poly(β-amino ester) network polymers
    (Wiley, 2017) Güven, Melek Naz; Altuncu, Merve Seçkin; Eren, Tuğce Nur; Avcı, Duygu; N/A; Department of Chemistry; Acar, Havva Funda Yağcı; Duman, Fatma Demir; PhD Student; Faculty Member; Department of Chemistry; Graduate School of Science and Engineering; College of Sciences; N/A; 178902
    Three novel bisphosphonate-functionalized secondary diamines are synthesized and incorporated into poly(beta-amino ester)s (PBAEs) to investigate the effects of bisphosphonates on biodegradation and toxicity of PBAE polymer networks. These three novel amines, BPA1, BPA2, and BPA3, were prepared from the reactions of 1,4-butanediamine, 1,6-hexanediamine, or 4,9-dioxa-1,12-dodecanediamine with tetraethyl vinylidene bisphosphonate, respectively. The PBAE macromers were obtained from the aza-Michael addition reaction of these amines to 1,6-hexane diol diacrylate (HDDA) and poly(ethylene glycol) diacrylate (PEGDA, M-n=575) and photopolymerized to produce biodegradable gels. These gels with different chemistries exhibited similar degradation behavior with mass loss of 53-73% within 24 h, indicating that degradation is mostly governed by the bisphosphonate group. Based on the in vitro cytotoxicity evaluation against NIH 3T3 mouse embryonic fibroblast cells, the degradation products do not exhibit significant toxicity in most cases. It was also shown that PBAE macromers can be used as cross-linkers for the synthesis of 2-hydroxyethyl methacrylate hydrogels, conferring small and customizable degradation rates upon them. The materials reported have potential to be used as nontoxic degradable biomaterials. (C) 2017 Wiley Periodicals, Inc.
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    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; Ünal, Özlem; Acar, Havva Funda Yağcı; PhD Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902
    Several 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.
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    Phosphonate-functionalized poly(b-amino ester) macromers as potential biomaterials
    (Wiley, 2018) Akyol, Ece; Tatliyuz, Mirac; Guven, Melek Naz; Avci, Duygu; N/A; Department of Chemistry; Acar, Havva Funda Yağcı; Duman, Fatma Demir; PhD Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902
    Biodegradability, hemocompatibility, resistance to protein adsorption, and strong interactions with hydroxyapatite (HAP)-based tissues such as dentin, enamel, and bone are important properties of phosphorus-containing biomaterials. Here, novel phosphonate-functionalized poly(-amino ester) (PBAE) macromers are synthesized through aza-Michael addition of various diacrylates [1,6-hexanediol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA, M-n=575), 1,4-butanediol diacrylate (BDDA), 1,6-hexanediol ethoxylate diacrylate (HDEDA) and triethylene glycol diacrylate (TEGDA)] and a phosphonate-containing primary amine (diethyl 2-aminoethylphosphonate, A1) efficiently without any catalyst; where replacement of A1 with propyl amine (PA) served as control. The macromers, whose molecular weight is ca. 1000-4000 Da as confirmed by both GPC and (1) H-NMR spectroscopy, are photopolymerized to give biodegradable gels. The degradation behavior and cell interaction of these gels are studied. The degradation rates of the gels can be varied by choice of starting acrylates and the acrylate:amine ratio. Furthermore, the gels showed slightly higher degradability than PA-based analogs (controls). Except TEGDA and PEGDA-based ones, all phosphonate-functionalized PBAE gels supported the attachment of larger number of SaOS-2 cells than nonphosphonated ones and the best film was found to be the one based on HDEDA-A1 with balanced hydrophilicity. Degradation products of these films have no significant cytotoxicity except HDDA-PA. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1390-1399, 2018.
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    Photo-responsive and enzymatically degradable click hydrogels for vascularized grafts
    (Mary Ann Liebert, Inc, 2022) N/A; N/A; Department of Chemistry; Department of Chemical and Biological Engineering; Nazeer, Muhammad Anwaar; Batool, Syeda Rubab; Kızılel, Seda; PhD Student, Researcher; Faculty Member; Department of Chemistry; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; N/A; N/A; 28376
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