Person: ÖZBAŞ, SUNA
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ÖZBAŞ
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SUNA
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Publication Metadata only Investigation of the Therapeutic Efficacy of Codelivery of psiRNA-Vascular Endothelial Growth Factor and pIL-4 into Chitosan Nanoparticles in the Breast Tumor Model(ELSEVIER SCIENCE INC, 2014) EREN, FATİH; Salva, Emine; Turan, Suna O.; Kabasakal, Levent; Alan, Saadet; Ozkan, Naziye; Eren, Fatih; Akbuga, JulideAngiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer. (c) 2013 Wiley Periodicals, Inc.Publication Open Access Plasmid DNA-loaded chitosan/TPP nanoparticles for topical gene delivery(INFORMA HEALTHCARE, 2011-04) ÖZBAŞ, SUNA; Ozbas-Turan, Suna; Akbuga, JulideTopical application of plasmid DNA represents an attractive route of gene delivery. Although chitosan (CS) has been widely investigated as a gene-carrier, there is very limited information about the skin application of CS-based systems for DNA. This study evaluated pDNA-loaded chitosan nanoparticles (CS-NPs) for skin gene delivery. NPs were prepared by inducing the gelation of CS upon interaction with sodium tripolyphosphate. pSV-beta-Gal was used as a reporter gene. The size, surface charge, and the other in vitro characteristics of CS-NPs were examined. Primary human dermal fibroblast cells (HDF) and mouse fibroblast NIH 3T3 cell lines (ATCC CCL-92) were used for in vitro transfection studies. In in vivo study, CS-NPs were applied to the skin of baby and adult Sprague Dawley rats by spreading on the shaved area of the back of animals. During a week animals were sacrificed and skin biopsies were taken for beta-Gal expression. beta-galactosidase enzyme activity was determined spectrophotometrically at 420 nm. The distribution of beta-galactosidase expressing cells within the skin tissue was observed by X-gal histochemical method. beta-galactosidase was continuously expressed at the nanoparticle-treated skin during the 7 days. High and continuous beta-Gal expressions were obtained with CS-NPs, although it was low in the first day. When a comparison was made between the data of baby and adult rats, markedly high transfection were measured in the skin samples of the baby rats. NPs protected pDNA against the enzyme and serum attacks. In conclusion, CS-NPs showed in vivo transfection potential in rats for skin gene delivery.Publication Metadata only Inhibition of Glomerular Mesangial Cell Proliferation by siPDGF-B- and siPDGFR-beta-Containing Chitosan Nanoplexes(SPRINGER, 2017) ÖZBAŞ, SUNA; Salva, Emine; Turan, Suna Ozbas; Akbuga, JulideMesangioproliferative glomerulonephritis is a disease that has a high incidence in humans. In this disease, the proliferation of glomerular mesangial cells and the production of extracellular matrix are important. In recent years, the RNAi technology has been widely used in the treatment of various diseases due to its capability to inhibit the gene expression with high specificity and targeting. The objective of this study was to decrease mesangial cell proliferation by knocking down PDGF-B and its receptor, PDGFR-beta. To be able to use small interfering RNAs (siRNAs) in the treatment of this disease successfully, it is necessary to develop appropriate delivery systems. Chitosan, which is a biopolymer, is used as a siRNA delivery system in kidney drug targeting. In order to deliver siRNA molecules targeted at PDGF-B and PDGFR-beta, chitosan/siRNA nanoplexes were prepared. The in vitro characterization, transfection studies, and knockdown efficiencies were studied in immortalized and primary rat mesangial cells. In addition, the effects of chitosan nanoplexes on mesangial cell proliferation and migration were investigated. After in vitro transfection, the PDGF-B and PDGFR-beta gene silencing efficiencies of PDGF-B and PDGFR-beta targeting siRNA-containing chitosan nanoplexes were 74 and 71% in immortalized rat mesangial cells and 66 and 62% in primary rat mesangial cells, respectively. siPDGF-B- and siPDGFR-beta-containing nanoplexes indicated a significant decrease in mesangial cell migration and proliferation. These results suggested that mesangial cell proliferation may be inhibited by silencing of the PDGF-B signaling pathway. Gene silencing approaches with chitosan-based gene delivery systems have promise for the efficient treatment of renal disease.Publication Metadata only Topical Application of Antisense Oligonucleotide-Loaded Chitosan Nanoparticles to Rats(MARY ANN LIEBERT INC, 2010) SEZER, ALİ DEMİR; Ozbas-Turan, Suna; Akbuga, Juelide; Sezer, Ali DemirSkin delivery of antisense oligonucleotides (AsODNs) has exciting potential in the treatment of skin diseases. However, the therapeutic applications of oligonucleotide-based therapies are limited by the instability of these molecules toward nucleases, short half-life in vivo, and insufficient cellular uptake. The purpose of this study was to investigate in vivo antisense effect of AsODN-loaded chitosan nanoparticles after topical application. AsODN-loaded chitosan nanoparticles were topically applied to Sprague Dawley rats (adult and baby). At 1, 3, 6, 9, and 12 days posttransfection, animals' skin samples were taken for measurement of beta-galactosidase (beta-Gal) expression and histological control. After topical application of AsODN-loaded chitosan nanoparticles in different doses, beta-Gal expression reduced significantly. Highest inhibition was observed after 6 days of transfection of nanoparticles. Free AsODNs exhibited 35% of beta-Gal inhibition on the first day. beta-Gal expression was inhibited in approximately 82-85% with transfection of nanoparticles containing 30 mg AsODNs at 6 days. The antisense effect of AsODN-loaded chitosan nanoparticle in baby skin was evaluated at 6 days: 77-86% of beta-Gal suppression was measured and differences between the doses were not significant. Thus, chitosan nanoparticles are useful carrier for delivery of AsODNs into skin cells of rats and may be used for topical application on human skin.Publication Metadata only The enhancement of gene silencing efficiency with chitosan-coated liposome formulations of siRNAs targeting HIF-1 alpha and VEGF(ELSEVIER SCIENCE BV, 2015) EREN, FATİH; Salva, Emine; Turan, Suna Ozbas; Eren, Fatih; Akbuga, JulideRNA interference (RNAi) holds considerable promise as a novel therapeutic strategy in the silencing of disease-causing genes. The development of effective delivery systems is important for the use of small interfering RNA (siRNA) as therapy. In the present study, we investigated the effect on breast cancer cell lines and the co-delivery of liposomes containing siHIF1-alpha and siVEGF. In order to achieve the co-delivery of siHIF1-alpha and siVEGF and to obtain lower cytotoxicity, higher transfection and silencing efficiency, in this study, we used chitosan-coated liposomal formulation as the siRNA delivery system. The obtained particle size and zeta potential values show that the chitosan coating process is an effective parameter for particle size and the zeta potential of liposomes. The liposome formulations loaded with siHIF1-alpha and siVEGF showed good stability and protected siRNA from serum degradation after 24-h of incubation. The expression level of VEGF mRNA was markedly suppressed in MCF-7 and MDA-MB435 cells transfected with chitosan-coated liposomes containing siHIF1-alpha and VEGF siRNA, respectively (95% and 94%). In vitro co-delivery of siVEGF and siHIF1-alpha using chitosan-coated liposome significantly inhibited VEGF (89%) and the HIF1-alpha (62%) protein expression when compared to other liposome formulations in the MDA-MB435 cell. The co-delivery of siVEGF and siHIF1-alpha was greatly enhanced in the vitro gene silencing efficiency. In addition, chitosan-coated liposomes showed 96% cell viability. Considering the role of VEGF and HIF1-alpha in breast cancer, siRNA-based therapies with chitosan coated liposomes may have some promises in cancer therapy. (C) 2014 Elsevier B.V. All rights reserved.