Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Author: search.filters.author.Dağlıoğlu, CenkScopus Q: search.filters.scopusQuartile.Q1

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Now showing 1 - 4 of 4
  • Article
    Citation - WoS: 43
    Citation - Scopus: 61
    Current 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: 15
    Citation - Scopus: 13
    Cascade 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 Necmiye
    Chemotherapy 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
    Citation - WoS: 15
    Citation - Scopus: 13
    Environmentally 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, Cenk
    Drug 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: 39
    Citation - Scopus: 37
    Enhancing Tumor Cell Response To Multidrug Resistance With Ph-Sensitive Quercetin and Doxorubicin Conjugated Multifunctional Nanoparticles
    (Elsevier Ltd., 2017) Dağlıoğlu, Cenk
    Classical 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.