Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

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

Browse

Filters

2017 - 20192

Settings

Institution Author: search.filters.institutionAuthor.Dağlıoğlu, CenkPublisher: search.filters.publisher.Elsevier Ltd.

Search Results

Now showing 1 - 2 of 2
  • 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: 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.