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ÖZBAŞ, SUNA

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ÖZBAŞ

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SUNA

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2016 - 20172
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    PublicationOpen Access
    In vitro gene silencing effect of chitosan/shRNA PDGF-D nanoparticles in breast cancer
    (MARMARA UNIV, FAC PHARMACY, 2017-10-03) EKENTOK ATICI, CEYDA; Ekentok, Ceyda; Turan, Suna Ozbas; Akbuga, Julide
    Breast cancer is the most common cancer worldwide in women and it is highly malignant and fatal. PDGF-D plays role in regulation of many cellular processes such as angiogenesis. PDGF-D is overexpressed in many types of cancers and promote tumor growth and metastasis. Silencing of PDGF-D gene by using shRNA with an appropriate carrier system may decrease tumor growth and metastasis. In our study, we prepared chitosan nanoparticles loaded with five different shRNA plasmids targeting different exons of PDGF-D gene. Then, nanoparticles were characterized in vitro and transfection efficiency of these nanoparticles were investigated in breast cancer cell lines (MCF7, MDA-MB-231 and MDA-MB-435). The effects of single and multiple shRNA sequences, molecular weight of chitosan (150 kDa and 400 kDa) and the amount of shRNA (100 and 500 mu g) on the characterization and transfection efficiencies of nanoparticles have been studied. Size of nanoparticles changed between 200-400 nm and approximately 95-100% encapsulation efficiency were obtained. Release of shRNA changed with the molecular weight of chitosan. It was obtained that formulation containing shRNA plasmid targeting PDGF-D exon 6 (NP1) has the highest silencing efficiency in MDA-MB-231 cell line. It was also evaluated that chitosan can be a suitable gene delivery system for shRNA targeting PDGF-D.
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    PublicationOpen Access
    In Vitro PDGF-B Gene Silencing Studies and In Vivo Delivery of siRNA to the Rat Kidney Using Chitosan/siRNA Nanoplexes
    (MARMARA UNIV, FAC MEDICINE, 2016-05-12) ÖZBAŞ, SUNA; Salva, Emine; Ozbas Turan, Suna; Alan, Saadet; Akbuga, Julide
    The targeting of specific genes responsible from onset and progression of kidney diseases offer a new therapeutic strategy in the field of renal gene therapy. The altered expression of platelet derived growth factor (PDGF) is an important marker of renal diseases. In this study, we investigated in vitro gene silencing efficiency of chitosan nanoplexes containing PDGF-B and PDGFR-beta targeted siRNAs in the kidney cell lines including HEK-293 and MDCK and delivery to the kidney as an in vivo delivery system. As a result, PDGF-B expression was significantly inhibited by co-delivery of chitosan/siPDGF-B+siPDGFR-beta nanoplexes prepared using in the different weight ratios (10/1, 20/1 and 50/1). When 20/1 and 50/1 weight ratios of chitosan nanoplexes were i.v. injected to rats, chitosan/FITC-siPDGFB nanoplexes were reached to kidney tissue at 4 h after intravenous injection. These results suggest that delivery of siRNA using chitosan nanoplexes may be effective for the therapy of kidney diseases.