1 Ocak 2017 Dergi makalesi Açık Erişim

Bakan, Feray; Kara, Goknur; Cakmak, Melike Cokol; Cokol, Murat; Denkbas, Emir Baki

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    <subfield code="a">Synthesis and characterization of amino acid-functionalized calcium phosphate nanoparticles for siRNA delivery</subfield>
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    <subfield code="a">Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20-27 nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi technology has emerged as a promising method for the treatment of a variety of diseases. However, a major limitation in the therapeutic use of siRNA is its rapid degradation in plasma and cellular cytoplasm, resulting in short half-life. In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is required to use a carrier system for its delivery. In this work, chemically and morphologically different calcium phosphate (CaP) nanoparticles, including spherical-like hydroxyapatite (HA-s), needle-like hydroxyapatite (HA-n) and calcium deficient hydroxyapatite (CDHA) nanoparticles were synthesized by the sol-gel technique and the effects of particle characteristics on the binding capacity of siRNA were investigated. In order to enhance the gene loading efficiency, the nanoparticles were functionalized with arginine and the morphological and their structural characteristics were analyzed. The addition of arginine did not significantly change the particle sizes; however, it provided a significantly increased binding of siRNA for all types of CaP nanoparticles, as revealed by spectrophotometric measurements analysis. Arginine functionalized HA-n nanoparticles showed the best binding behavior with siRNA among the other nanoparticles due to its high, positive zeta potential (+18.8 mV) and high surface area of Ca++ rich "c" plane. MIT cytotoxicity assays demonstrated that all the nanoparticles tested herein were bio compatible. Our results suggest that high siRNA entrapment in each of the three modified non-toxic CaP nanoparticles make them promising candidates as a non-viral vector for delivering therapeutic siRNA molecules to treat cancer. (C) 2017 Elsevier B.V. All rights reserved.</subfield>
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    <subfield code="u">Hacettepe Univ, Biochem Div, Dept Chem, TR-06800 Ankara, Turkey</subfield>
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    <subfield code="u">Tufts Univ, Sch Med, Dept Mol Biol &amp; Microbiol, Harvard Med Sch,Lab Syst Pharmacol, Boston, MA 02111 USA</subfield>
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    <subfield code="a">Denkbas, Emir Baki</subfield>
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    <subfield code="u">Sabanci Univ, Nanotechnol Res &amp; Applicat Ctr, SUNUM, TR-34956 Istanbul, Turkey</subfield>
    <subfield code="a">Bakan, Feray</subfield>
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