Person: EKENTOK ATICI, CEYDA
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EKENTOK ATICI
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CEYDA
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Publication Metadata only Hedeflendirilmiş Nanopartiküllerin transdermal taşınması ve in vitro değerlendirilmesi(Jenny Stanford Publishing, 2021-11-01) EKENTOK ATICI, CEYDA; SEZER, ALİ DEMİR; ÇELİK, AYSUN; Ekentok Atıcı C., Çelik A., Sezer A. D.Publication Metadata only Administration of Ad5 chitosan PEG-aptamer vector delivering PDGF-D shRNA decreases tumor growth in rat breast cancer model(2021-10-01) EKENTOK ATICI, CEYDA; Ekentok-Atici C., Akbuga J.Publication Open Access Viral vector platforms within the gene therapy landscape(2023-01-01) EKENTOK ATICI, CEYDA; EKENTOK ATICI C.Gene therapy is the treatment of a disease through transferring genetic material (DNA/RNA) into the cells of patients. The transferred gene can act following ways: (i) enabling expression of the transferred gene, (ii) inhibiting the expression of a target gene and (iii) modifying a target gene. Gene therapy clinical trials started nearly fifty years ago with treatment of inherited monogenic disorder. Soon after that, gene therapy based clinical approaches was extended to acquired diseases such as cancer [1]. Since the first successful gene therapy clinical trial on a four-year girl who had ADA deficiency was initiated in 1990, more than 30 gene therapy products have been approved worldwide by different authorities [2]. Several approaches like physical methods (electroporation, microinjection, biolistic etc.), chemical methods (polymers, lipids, peptides etc.) and biological methods (adenoviruses, adeno-associated viruses, retroviruses etc.) can be employed to deliver the DNA inside cells. No single method works best for all applications. Factors that determine the choice of the method include cost, reproducibility, toxicity, mechanism of delivery, ease of use, and efficiency [3]. Adenoviral vectors (Ads), adeno-associated viral vector (AAVs), retroviral vectors (RVs) and lentiviral vectors (LVs) are the most common viral delivery systems for gene therapy applications. These systems have the benefits of high transfection potency and constant expression of therapeutic genes. However, limitations in large scale virus production, immunogenicity, toxicity and insertional mutagenesis are their common disadvantages. Current strategies to overcome these disadvantages are; (i) localized delivery and transcriptional targeting for toxicity and off-target effects (ii) immunosuppressive drugs and anti-inflammatory agents for immune response and (iii) biomaterial-mediated viral gene delivery [4]. The polymers can be used for viral vector modification and evolving hybrid vectors is a promising strategy for gene therapy applications. Surface modification of Ads with cationic polymers can be done by (i) non-covalent coating (physical modification) (ii) covalent coating (chemical modification). Non-covalent coating strategies gain attention because of ease of manipulation [5]. In our recent study we aimed to prepare Ad/chitosan hybrid vector to deliver shPDGF-D in breast cancer cell line MDA-MB-231. We covalently coat Ad surface with different amount and molecular weight chitosan and investigate gene silencing efficiency of vectors. In vitro cell culture studies showed that both low and high molecular weight chitosan increased PDGF-D silencing efficiency of Ad5 vector at 48 hours significantly. Also, the invasion ability of MDA-MB-231 cells decreased after treatment with coated Ad vector correlated with PDGF-D silencing results [6]. In conclusion, the results showed that non-covalent modification of Ad surface with polymers increased in vitro silencing efficiency, which may allow decrease viral dose for safer and efficient therapy.Publication Metadata only Investigation of antineoplastic activity of achillea nobilis subsp. Neilreichii plant in experimental breast cancer(2019-07-03) YAVUZ, AYŞE NUR; EKENTOK ATICI, CEYDA; TAŞKIN, TURGUT; ÖZBAŞ, SUNA; KABASAKAL, LEVENT; Sehlan S. S., Yavuz A. N., Ekentok Atıcı C., Taşkın T., Alan S., Özbaş S., Kabasakal L.Publication Metadata only Mammaglobin gen ekspresyonunun kitozan/siRNA nanopleksleri ile baskılanması ve in vitro karakterizasyonu(2018-11-16) EKENTOK ATICI, CEYDA; ÖZBAŞ, SUNA; Özkavak Ş. B., Ekentok Atıcı C., Şalva E., Özbaş S.Publication Metadata only The effects of some traditional medical plants and beta amyloid protein in cell viability(2019-07-03) YAVUZ, AYŞE NUR; EKENTOK ATICI, CEYDA; TAŞKIN, TURGUT; ÖZBAŞ, SUNA; KABASAKAL, LEVENT; Saleh Al-Rabeei M. A., Yavuz A. N., Ekentok Atıcı C., Taşkın T., Özbaş S., Kabasakal L.Publication Metadata only Chitosan-based delivery of CRISPR-Cas9 plasmid in breast cancer stem cells(2023-01-01) EKENTOK ATICI, CEYDA; ÖZBAŞ, SUNA; Canak-Ipek T., Avci-Adali M., EKENTOK ATICI C., ŞALVA E., ÖZBAŞ S.© 2023 Marmara University Press.Clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease system (CRISPR/Cas9) has emerged as a powerful toolbox for cancer therapy, serving as a gene fixed-point knock-out method. However, suitable gene carrier systems are urgently needed to encapsulate the CRISPR/Cas9 system and to improve the uptake into the cancer cells for anti-cancer therapy. In cancer therapy, breast cancer stem cells should be also targeted besides tumor cells. In this study, we prepared chitosan/CRISPR-Cas9/protamine nanoplexes and performed in vitro characterization. The results showed that the chitosan/protamine complex increased the zeta potential of the VEGF CRISPR/Cas9 plasmid from negative to positive. In vitro cell culture studies showed that VEGF silencing efficiency was 46.19% and 30.2% in MCF-7 and MCF-7s, respectively, after 7 days. The invasion capacity of cancer cells decreased significantly for both cell types. The results indicate that chitosan/VEGF CRISPR/Cas9 plasmid/protamine complexes can be used to reduce VEGF expression, leading to a decrease in the invasion capacity of breast cancer as well as breast cancer stem cells and providing proof of concept for more advanced studies, including in vivo studies, of this system.Publication Metadata only Kitozan/mammaglobin shRNA nanoplekslerinin hazırlanması ve in vitro karakterizasyonu(2018-11-16) ÖZBAŞ, SUNA; EKENTOK ATICI, CEYDA; Özkan A., Ekentok Atıcı C., Şalva E., Özbaş S.Meme kanseri kadınlar arasında dünyada en sık görülen malign tümörlerden biridir. İnsan mammaglobin (hMAM), genellikle meme ve meme kanseri hücrelerinde eksprese edilen bir glikoproteindir. Meme spesifik hMAM’ın RNA interferans (RNAi) teknolojisi ile short hairpin RNA (shRNA) kullanılarak baskılanması önemli bir gen tedavi stratejisidir. Nükleaz degredasyonundan korunma ve hücreye giriş etkinliğini arttırmak için viral olmayan gen taşıyıcı sistem olarak kitozan; biyobozunur olması, toksik olmayışı ve katyonik yapısı sebebiyle sıklıkla tercih edilmektedir. Bu çalışmada da, hMAM genini baskılama amacıyla kitozan/mammaglobin shRNA nanopleksleri hazırlanmıştır. Bu amaçla, transformasyon sonrası [1] izole edilen shRNA’nın spektrofotometrik ve elektroforetik kontrolleri yapılmıştır [2]. Elektrostatik etkileşim yöntemiyle farklı oranlarda (0.5/1, 1/1, 2/1, 3/1, 4/1, 5/1; a/a) kitozan/shRNA nanopleksleri hazırlanarak partikül boyutu, zeta potansiyel, jel elektroforez ve serum stabilitesi analizleri yapılmıştır. Elektroforez sonuçlarına göre tam kompleks oluşumu gözlenmiş ve orana bağlı olarak nanopleks boyutlarının 153.2 ile 436.3 nm arasında, zeta potansiyel değerlerinin de +0.6 ile +31.9 mV arasında olduğu belirlenmiştir. Serum stabilitesi sonuçlarına göre hazırlanan nanoplekslerin shRNA’yı degredasyondan koruduğu görülmüştür. Elde edilen sonuçlar ışığında, hazırlanan formülasyonların meme kanseri tedavisindeki etkinliğinin araştırılması için ileri in vitro ve in vivo çalışmalar planlanmaktadır.