Dağlıoğlu, Cenk
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Daglioglu, C.
Daglioglu, C
Daglioglu, Cenk
Dağlıoğlu, C
Dağlıoğlu, C.
Daglioglu, C
Daglioglu, Cenk
Dağlıoğlu, C
Dağlıoğlu, C.
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04.03. Department of Molecular Biology and Genetics
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283
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11
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11
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262
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289
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WoS Citations per Publication
23.82
Scopus Citations per Publication
26.27
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10
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| Journal | Count |
|---|---|
| Politeknik Dergisi | 2 |
| Bioconjugate Chemistry | 1 |
| Colloids and Surfaces B: Biointerfaces | 1 |
| Drug Design Development And Therapy | 1 |
| International Journal of Molecular Sciences | 1 |
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Now showing 1 - 10 of 11
Article Citation - WoS: 1Pasif Tümör Hedefli İnorganik İlaç Nanotaşıyıcıların Akciğer Sağlıklı ve Kanser Hücreleri Üzerindeki Uzun Dönemli Etkisi(Gazi Üniversitesi, 2020) Dağlıoğlu, Cenk; Kacı, Fatma Necmiyeİlaç nanotaşıyıcıları, kontrollü ve sürekli ilaç salım özellikleri ile kanser tedavisinde büyük bir potansiyele sahiptir. Bu nanotaşıyıcılar pasif veya aktif hedefli olarak ilaç taşınımı sağlayabilmektedir, ancak aktif hedefli muadillerine göre, pasif hedefli nanotaşıyıcılar tümörlü dokularda daha yavaş ve düşük düzeyde ilaç birikimi sağladığından kanserli hücrelerin yanında sağlıklı hücrelerde uzun süre bu nanotaşıyıcılara maruz kalmaktadır. Bu nedenle, bu çalışmada, pasif hedefli ilaç nanotaşıyıcıların insan akciğer epitel BEAS-2B hücreleri ve insan akciğer kanser A549 hücreleri üzerindeki uzun dönem etkileri araştırıldı. Bunun için, görüntüleme ve tedavi edici özellikleri bir arada barından Fe3O4@SiO2(FITC)-DOX formülasyonuna sahip ilaç nanotaşıyıcıları kullanıldı ve hücresel birikim, sitotoksisite ve apoptoz üzerindeki etkileri araştırıldı. Hücresel alım ve sitotoksisite deneyleri, pasif hedefli nanotaşıyıcıların kanser hücresi canlılığının etkin bir şekilde azalttığını gösterirken, 24 saatlik inkübasyon sürecinde sağlıklı hücreler üzerinde kayda değer bir etki görülmedi. Ancak 96 saatlik uzun inkübasyon sürecinde, sağlıklı BEAS-2B hücreleri makul seviyelerde nanotaşıyıcı alımı gerçekleştirirken, A549 kanser hücrelerine kıyasla düşük düzeylerde ilaç-aracılı sitotoksisite sergiledi. Ayrıca, nanotaşıyıcılar A549 hücrelerindeki apoptoz seviyelerini önemli ölçüde artırırken, BEAS-2B hücrelerinde 96 saat sonunda dahi apoptotik etki göstermedi. Bu sonuçlar, pasif hedefli inorganik ilaç nanotaşıyıcıların, sağlıklı hücreleri ihmal edilebilir düzeyde etkileyerek, antikanser ilaçların kemoterapötik etkilerini artırmada umut verici olduğunu göstermektedir.Article Citation - WoS: 104Citation - Scopus: 123The Role of Cysteine Cathepsins in Cancer Progression and Drug Resistance(MDPI, 2019) Rudzinska, Magdalena; Parodi, Alessandro; Soond, Surinder M.; Vinarov, Andrey Z.; Korolev, Dmitry O.; Morozov, Andrey O.; Zamyatnin, Andrey A., Jr.; Dağlıoğlu, Cenk; Tutar, YusufCysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associated with highly aggressive tumor phenotypes, their mechanistic role in cancer progression is still to be determined to develop new therapeutic strategies. In this review, we highlight the literature related to the role of the cysteine cathepsins in cancer biology, with particular emphasis on their input into tumor biology.Article Citation - WoS: 15Citation - Scopus: 13Cascade Therapy With Doxorubicin and Survivin-Targeted Tailored Nanoparticles: an Effective Alternative for Sensitization of Cancer Cells To Chemotherapy(Elsevier Ltd., 2019) Dağlıoğlu, Cenk; Kacı, Fatma NecmiyeChemotherapy frequently involves combination treatment protocols to maximize tumor cell killing. Unfortunately these intensive chemotherapeutic regimes, often show disappointing results due to the development of drug resistance and higher nonspecific toxicity on normal tissues. In cancer treatment, it is critically important to minimize toxicity while preserving efficacy. We have previously addressed this issue and proposed a nanoparticle-based combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent for neutralizing antiapoptotic survivin (BIRC5) to potentiate the efficacy of doxorubicin (DOX). Although the particles exhibited strong anticancer effect on the lung carcinoma A549 and the cervical carcinoma HeLa cells, there were lower-level therapeutic outcomes on the colon carcinoma HCT-116, the leukemia Jurkat and the pancreatic carcinoma MIA PaCa-2 cells. Since targeted therapies are one of the key approaches for overcoming drug resistance, tailoring the treatment of cancer cells with distinct characteristics is necessary to improve the therapeutic outcome of cancer therapy and to minimize potential pharmacokinetic interactions of drugs. In the light of this issue, this study examined whether a cascade therapy with low-dose DOX and survivin-targeted tailored nanoparticles is more effective at sensitizing HCT-116, Jurkat and MIA PaCa-2 cancer cells to DOX-chemotherapy than simultaneous combination therapy. The results demonstrated that the sequential therapy with the protocol comprising addition of the nanoparticles after incubation of cells with DOX clearly advanced the therapeutic outcome of related cancer cells, whereas the reverse protocol resulted in a reduction or delay in apoptosis, emphasizing the critical importance of formulating synergistic drug combinations in cancer therapy.Article İlaç Taşıma Sistemleri Olarak Nanopartiküller Kullanılarak Pasif ve Aktif Tümör Hedeflemelerinin Karşılaştırmalı İncelenmesi(Akademik Perspektif Derneği, 2018) Dağlıoğlu, CenkNanopartikül-aracılı ilaç hedefleme kanser araştırmalarının aktif bir alanı olup, tümör dokusuna özgün antikanser etkinliği artırmada çok önemli bir potansiyele sahiptir. Bu çalışmada, hedefleme verimlilik oranlarının belirlenmesi için pasif ve aktif hedefli nanopartiküllerin tümör hedefleme kabiliyetleri, sırasıyla artmış geçirgenlik ve alıkonma (EPR) etkisi ve biyotin reseptörlerini hedefleme yaklaşımları karşılaştırılarak incelendi. Bunun için, görüntüleme ve tedavi edici özellikleri bir arada barından Fe3O4@SiO2(FITC)-DOX (pasif hedefleme için) ve Fe3O4@SiO2(FITC)-BTN/DOX (aktif hedefleme için) multifonksiyonel nanopartikülleri kullanıldı. Nanopartiküllerin tümör hücrelerindeki birikiminin izlenmesi ve miktarsal ölçümü için floresan mikroskopu ve akım sitometresi kullanıldı. Elde edilen sonuçlar, pasif hedeflemeyle karşılaştırıldığında aktif hedefleme stratejisinin servikal karsinoma HeLa hücrelerindeki nanopartikül birikimini 2 kat gibi önemli bir ölçüde artırdığını gösterdi. Aktif hedefli nanopartiküller, pasif hedefli nanopartikülerden yaklaşık 2.5 kat daha düşük yarı-maksimum inhibisyon konsantrasyonu (IC50) değeri ile kanser hücrelerinde daha yüksek sitotoksisite sergiledi. Ayrıca, pasif hedefli nanopartiküllerle karşılaştırıldığında, aktif hedefli nanopartiküllerin apoptotik hücre sayısını yaklaşık % 21.1 oranında artırdığı bulundu. Bu gözlemler, aktif tümör hedefli ilaç taşıma sistemlerinin, pasif tümör hedefli ilaç taşıma sistemleri ile karşılaştırıldığında, antikanser ilaçların kemoterapötik etkilerini artırmada daha umut verici olduğunu göstermektedir.Article Citation - WoS: 25Citation - Scopus: 23Synthesis and Characterization of Aicar and Dox Conjugated Multifunctional Nanoparticles as a Platform for Synergistic Inhibition of Cancer Cell Growth(American Chemical Society, 2016) Dağlıoğlu, Cenk; Okutucu, BurcuThe success of cancer treatment depends on the response to chemotherapeutic agents. However, malignancies often acquire resistance to drugs if they are used frequently. Combination therapy involving both a chemotherapeutic agent and molecularly targeted therapy may have the ability to retain and enhance therapeutic efficacy. Here, we addressed this issue by examining the efficacy of a novel therapeutic strategy that combines AICAR and DOX within a multifunctional platform. In this context, we reported the bottom-up synthesis of Fe3O4@SiO2(FITC)-FA/AICAR/DOX multifunctional nanoparticles aiming to neutralize survivin (BIRC5) to potentiate the efficacy of DOX against chemoresistance. The structure of nanoparticles was characterized by dynamic light scattering (DLS), zeta-potential measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and electron microscopy (SEM and STEM with EDX) techniques. Cellular uptake and cytotoxicity experiments demonstrated preferentially targeted delivery of nanoparticles and an efficient reduction of cancer cell viability in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat, and MIA PaCa-2). These results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility. This novel approach which combines AICAR and DOX within a single platform might be promising as an antitumor treatment for cancer.Article Citation - WoS: 43Citation - Scopus: 61Current Status and Perspectives of Protease Inhibitors and Their Combination With Nanosized Drug Delivery Systems for Targeted Cancer Therapy(Dove Medical Press Ltd, 2021) Rudzinska, Magdalena; Dağlıoğlu, Cenk; Savvateeva, Lyudmila, V; Kaci, Fatma Necmiye; Antoine, Rodolphe; Zamyatnin, Andrey A., Jr.In cancer treatments, many natural and synthetic products have been examined; among them, protease inhibitors are promising candidates for anti-cancer agents. Since dysregulated proteolytic activities can contribute to tumor development and metastasis, antagonization of proteases with tailored inhibitors is an encouraging approach. Although adverse effects of early designs of these inhibitors disappeared after the introduction of next-generation agents, most of the proposed inhibitors did not pass the early stages of clinical trials due to their nonspecific toxicity and lack of pharmacological effects. Therefore, new applications that modulate proteases more specifically and serve their programmed way of administration are highly appreciated. In this context, nanosized drug delivery systems have attracted much attention because preliminary studies have demonstrated that the therapeutic capacity of inhibitors has been improved significantly with encapsulated formulation as compared to their free forms. Here, we address this issue and discuss the current application and future clinical prospects of this potential combination towards targeted protease-based cancer therapy.Article Citation - WoS: 39Citation - Scopus: 37Enhancing Tumor Cell Response To Multidrug Resistance With Ph-Sensitive Quercetin and Doxorubicin Conjugated Multifunctional Nanoparticles(Elsevier Ltd., 2017) Dağlıoğlu, CenkClassical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance. The physicochemical properties of the nanoparticles were characterized based on the combination of several techniques: dynamic light scattering (DLS), zeta-potential measurement, Fourier transform infrared spectroscopy (FTIR), electron microscopy techniques (SEM and STEM with EDX) and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated enhanced intracellular delivery and retention of nanoparticles in the cytoplasm and efficient reduction of cancer cell viability in drug-resistant lung carcinoma A549/DOX cell lines. This did not affect internalization and viability of an immortalized human lung epithelial cell line BEAS-2B. Moreover, proapoptotic and antiproliferative studies showed that Fe3O4@SiO2(FITC)-BTN/QUR/DOX nanoparticles can promote apoptosis, inhibit tumor cell proliferation, and enhance the chemotherapeutic effects of DOX against multidrug resistance. These results confirm that this multifunctional platform possesses significant synergy between QUR and DOX and is promising for development as an antitumor treatment in cancer therapy.Article Citation - WoS: 3Citation - Scopus: 3Cloning, Expression, and Activity Analysis of Human Cathepsin C in the Yeast Pichia Pastoris(TUBITAK, 2017) Dağlıoğlu, CenkThe yeast Pichia pastoris expression system was investigated for the production of human cathepsin C (CatC) recombinant protein. The full-length CatC cDNA, corresponding to amino acids 12-475, was synthesized from interleukin-2 (IL-2) stimulated human peripheral blood mononuclear cells and subcloned in the pGEM-T cloning vector. After confirming the DNA sequence of the insert, the gene was cloned into the pPICZαA expression vector under the control of the methanol-inducible alcohol oxidase (AOX1) promoter and transformed to P. pastoris X-33 cells. The expressed protein was secreted into the culture medium through the α-factor mating signal sequence of the expression vector. Analysis of the culture supernatant revealed that the recombinant human CatC was secreted as a 58-kDa molecule, indicating that human CatC was accumulated in the culture supernatant as proform composed of the residual propart, the activation peptide, and the heavy and light chains. Extracellular recombinant proCatC was further activated by cysteine endoprotease papain in vitro and its activity was confirmed by assays using a synthetic substrate.Article Citation - WoS: 15Citation - Scopus: 13Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux(John Wiley and Sons Inc., 2018) Dağlıoğlu, CenkDrug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe3O4@SiO2(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe+2/Fe+3 salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.Article Citation - WoS: 1İnsan Kolon Kanseri Hücrelerine Karşı İnorganik Nanopartikül-temelli İlaç Taşıyıcı Sistemlerin Kullanılması: Partikül Büyüklüğünün Antikanser Aktivitesine Etkisi(Gazi Üniversitesi, 2020) Dağlıoğlu, CenkToday's nanoparticle technology enables the synthesis of nanoparticle-based drug delivery systems with desired size, shape, and materials especially for the applications of cancer nanomedicine. Thereby, understanding impact of particle sizes on anticancer activity will contribute to development of new drug delivery systems in cancer therapy. For this reason, in this study, two different sized nanoparticles (with -55 and 314 nm) were used as drug delivery systems and the effects of their size on the cellular uptake, cytotoxicity and apoptosis were investigated against the human colon carcinoma Caco-2 and HCT-116 cells. The results demonstrated that small nanoparticles promoted fast nanoparticle accumulation in both cancer cells in comparison to large particles. Small nanoparticles exhibited higher cytotoxicity in cancer cells with lower half maximal inhibitory concentration (IC50) values than large nanoparticles in 48 h. On the other hand, both nanoparticles showed similar IC50 values after 72 h prolonged exposure. Moreover, it was found that small nanoparticles increased the number of apoptotic cells in 24 h, whereas large nanoparticles induced apoptosis when exposure time increased to 72 h. These observations show that small sized drug delivery systems could be more efficient for improving the anticancer effects of chemotherapeutic drugs against human colon carcinoma as compared to large sized drug delivery systems.