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    Delivery of siRNA using hyaluronic acid-guided nanoparticles for downregulation of CXCR4
    (Wiley, 2023) Tunali, Beste Cagdas; Celik, Eda; Yildiran, Fatma Azize Budak; Turk, Mustafa
    In this study, effective transport of small interfering RNAs (siRNAs) via hyaluronic acid (HA) receptor was carried out with biodegradable HA and low-molecular weight polyethyleneimine (PEI)-based transport systems. Gold nanoparticles (AuNPs) capable of giving photothermal response, and their conjugates with PEI and HA, were also added to the structure. Thus, a combination of gene silencing, photothermal therapy and chemotherapy, has been accomplished. The synthesized transport systems ranged in size, between 25 and 690 nm. When the particles were applied at a concentration of 100 mu g mL(-1) (except AuPEI NPs) in vitro, cell viability was above 50%. Applying radiation after the conjugate/siRNA complex (especially those containing AuNP) treatment, increased the cytotoxic effect (decrease in cell viability of 37%, 54%, 13%, and 15% for AuNP, AuPEI NP, AuPEI-HA, and AuPEI-HA-DOX, respectively) on the MDA-MB-231 cell line. CXCR4 gene silencing via the synthesized complexes, especially AuPEI-HA-DOX/siRNA was more efficient in MDA-MB-231 cells (25-fold decrease in gene expression) than in CAPAN-1 cells. All these results demonstrated that the synthesized PEI-HA and AuPEI-HA-DOX conjugates can be used as siRNA carriers that are particularly effective, especially in the treatment of breast cancer.
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    Effects of B2O3 (boron trioxide) on colon cancer cells: our first-step experience and in vitro results
    (Tubitak Scientific & Technical Research Council Turkey, 2019) Albuzi, Ozgur; Dulger, Dilek; Tunali, Beste Cagdas; Aydin, Feray; Yalcin, Selim; Turk, Mustafa
    Boron oxide (B2O3) is derived from dehydration of boric acid and is a colorless, semitransparent, crystalline compound that is moderately soluble in water. On the other hand, boron oxide is chemically hygroscopic. This gives the molecule the ability to soak up water and adhere to tissues. Boron oxide can be used locally after tumor debulking in inoperable tumors and especially when the twnor-free margin distance cannot be provided. For all these reasons we aimed to evaluate the in vitro test results of B2O3, in terms of cytotoxicity, genotoxicity, apoptosis, and necrotic effects on L929 fibroblast cells and DLD-1 colorectal adenocarcinoma cells. Our studies demonstrated that boron oxide compounds appear to be highly cytotoxic for both cell lines according to WST cell viability assay (44.22% and 18.36% on DLD-1 and L929, respectively). Although no genotoxic effects were observed, boron oxide compounds showed antiproliferative effects for both cell lines. The prepared boron oxide compounds may hold the potential to be applied locally to the remaining tissue after surgery and further research and evaluation will be needed to determine its effectivenesss.
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    Phosphorus-nitrogen compounds. Part 48. syntheses of the phosphazenium salts containing 2-pyridyl pendant arm: structural characterizations, thermal analysis, antimicrobial and cytotoxic activity studies
    (NATL INST SCIENCE COMMUNICATION-NISCAIR, 2020) Elmas, Gamze; Okumus, Aytug; Kilic, Zeynel; Ozbeden, Pelin; Acik, Leyla; Tunali, Beste Cagdas; Turk, Mustafa
    The phosphazenium salts (protic ionic liquids, PILs/protic molten salts, PMOSs) (6a-6d and 7a) of the free phosphazene bases (4a-4d and 5a) have been prepared by the reactions of the corresponding cyclotriphosphazenes with the bulky gentisic acid. The structures of the PMOS have been evaluated using the elemental analyses, FTIR, H-1, C-13{H-1} and P-31{H-1} NmR data. The molecular and crystal structures of 4a and 6c are established by X-ray crystallography. The thermal properties of the PMOS are determined using TG and DTA techniques. On the other hand, the antimicrobial activities of the free phosphazene bases (4a-4d and 5a-5d) and PMOSs (6a-6d and 7a) are screened against the selected bacteria and yeast strains. The antimicrobial activities of the free phosphazene bases and the PMOSs are compared. The interactions of the phosphazenes and their salts with plasmid DNA are elucidated by the agarose gel electrophoresis. The evaluations of the cytotoxic activities of these compounds are also studied against to L929 fibroblast and breast cancer cells (MDA-MB-231).
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    Production of Reduced Graphene Oxide by Using Three Different Microorganisms and Investigation of Their Cell Interactions
    (Amer Chemical Soc, 2023) Utkan, Guldem; Yumusak, Gorkem; Tunali, Beste Cagdas; Ozturk, Tarik; Turk, Mustafa
    Despite the hugeand efficient functionalities of reduced grapheneoxide (RGO) for bioengineering applications, the use of harsh chemicalsand unfavorable techniques in their production remains a major challenge.Microbial production of reduced graphene oxide (RGO) using specificbacterial strains has gained interest as a sustainable and efficientmethod. The reduction of GO to RGO by selected bacterial strains wasachieved through their enzymatic activities and resulted in the removalof oxygen functional groups from GO, leading to the formation of RGOwith enhanced structural integrity. The use of microorganisms offersa sustainable approach, utilizing renewable carbon sources and mildreaction conditions. This study investigates the production of RGOusing three different bacterial strains: Lactococcuslactis (L. Lactis), Lactobacillus plantarum (L. plantarum), and Escherichia coli (E. coli) and evaluates its toxicity for safe utilization.The aim is to assess the quality of the produced RGO and evaluateits toxicity for potential applications. Thus, this study focusedon the microbial production of reduced graphene oxides well as theinvestigation of their cellular interactions. Graphite-derived grapheneoxide was used as a starting material and microbially reduced GO productswere characterized using the FTIR, Raman, XRD, TGA, and XPS methodsto determine their physical and chemical properties. FTIR shows thatthe epoxy and some of the alkoxy and carboxyl functional groups werereduced by E. coli and L. lactis, whereas the alkoxy groups were mostlyreduced by L. plantarum. The I (D)/I (G) ratio fromRaman spectra was found as 2.41 for GO. A substantial decrease inthe ratio as well as defects was observed as 1.26, 1.35, and 1.46for ERGO, LLRGO, and LPRGO after microbial reduction. The XRD analysisalso showed a significant reduction in the interlayer spacing of theGO from 0.89 to 0.34 nm for all the reduced graphene oxides. TGA resultsshowed that reduction of GO with L. lactis provided more reduction than other bacteria and formed a structurecloser to graphene. Similarly, analysis with XPS showed that L lactisprovides the most effective reduction with a C/O ratio of 3.70. Inthe XPS results obtained with all bacteria, it was observed that theC/O ratio increased because of the microbial reduction. Toxicity evaluationswere performed to assess the biocompatibility and safety of the producedRGO. Cell viability assays were conducted using DLD-1 and CHO celllines to determine the potential cytotoxic effects of RGO producedby each bacterial strain. Additionally, apoptotic, and necrotic responseswere examined to understand the cellular mechanisms affected by RGOexposure. The results indicated that all the RGOs have concentration-dependentcytotoxicity. A significant amount of cell viability of DLD-1 cellswas observed for L. lactis reducedgraphene oxide. However, the highest cell viability of CHO cells wasobserved for L. plantarum reduced grapheneoxide. All reduced graphene oxides have low apoptotic and necroticresponses in both cell lines. These findings highlight the importanceof considering the specific bacterial strain used in RGO productionas it can influence the toxicity and cellular response of the resultingRGO. The toxicity and cellular response to the final RGO can be affectedby the particular bacterial strain that is employed to produce it. This information will help to ensure that RGO is used safely in avariety of applications, including tissue engineering, drug deliverysystems, and biosensors, where comprehension of its toxicity profileis essential.
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    Synthesis and characterization of polyethyleneimine/silk fibroin/gold nanoparticle nanocomposites: Potential application as a gene carrier in breast cancer cell lines
    (Pergamon-Elsevier Science Ltd, 2023) Tunali, Beste Cagdas; Akturk, Omer; Sahingoz, Durukan; Turk, Mustafa; Keskin, Ayten Celebi
    There is a need in advancing the design of non-viral gene carriers, thus herein using the pulsed laser ablation in liquid (PLAL) technique, polyethyleneimine-capped gold nanoparticles (PEI-AuNPs) were synthesized and then combined with Bombyx mori silk fibroin (SF) to form the nanocomposites (PEI-SF-AuNPs). After the characterization analyses were carried out, PEI-AuNPs and PEI-SF-AuNPs were tested for their in vitro biocompatibility in MCF-7 and MDA-MB231 breast cancer cells. Finally, the transfection capability of the selected group was observed. PEI capping enabled the cationic modification of the AuNP surface and SF reduced the surface charge (from 35 to 4 mV). PEI-AuNPs were highly monodispersed in shape and size (8-9 nm). The nanoparticle group synthesized in 5% (w/v) PEI concentration (PEI-AuNP5) had increased cytotoxicity as compared to the group synthesized in 1% (w/v) PEI concentration (PEI-AuNP1), but the conjugation of SF with PEI-AuNPs alleviated this cytotoxic tendency significantly. The group (PEI-AuNP1) with the most negligible cytotoxicity proved to be successful in the transfection of siRNA analog, i.e., siGLO green transfection indicator. Overall, the PEI-AuNP1 nanocomposites could be suggested as potent siRNA carriers due to the above beneficial properties in genebased breast cancer therapies.
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    Synthesis of Bis(2,2,3,3-tetrafluoro-1,4-butanedialkoxy)-2-trans-6-bis(4-fluorobenzyl)spirocyclotetraphosphazene: Structural Characterization, Biological Activity and DFT Studies
    (SPRINGER/PLENUM PUBLISHERS, 2020) Elmas, Gamze; Kilic, Zeynel; Cosut, Bunyemin; Kesan, Gurkan; Acik, Leyla; Cam, Merve; Tunali, Beste Cagdas
    The Cl replacement reaction of octachlorocyclotetraphosphazene, N4P4Cl8 (1), with two equimolar amounts of N-(4-fluorobenzyl)-N'-methylpropane-1,3-diamine led to the formation of 4,4,8,8-tetrachloro-2-trans-6-bis-N-(4-fluorobenzyl)-N'-methylpropane-1,3-diamino-cyclotetraphosphazene (2). The reaction of 2 with excess sodium 2,2,3,3-tetrafluoro-1,4-butanedioxide afforded the bis(2,2,3,3-tetrafluoro-1,4-butanedialkoxy)-2-trans-6-bis(4-fluorobenzyespirocyclotetraphosphazene (2a). The elemental analyses, mass spectrum (ESI-MS), FTIR, HSQC, HMBC, H-1, C-13 and P-31 NMR spectral data of 2a were consistent with the proposed structure. The crystal structure of 2a was elucidated by X-ray diffraction method. The spectroscopic data of the molecules (2 and 2a) in the ground state were investigated by the Density Functional Theory (DFT) from the crystal structures. On the other hand, compound 2a was found to be the most active against S. aureus G(+) (MIC value: 125 mu M). Whilst, any antifungal activity of 2a was not observed against C. albicans and C. tropicalis. This compound also exhibits cytotoxic activity against L929 fibroblast and MCF-7 breast cancer cells. The interaction of 2a with pBR322 DNA was researched using gel electrophoresis. It is understood that the change in DNA conformation by interstrand of 2a with A/A and G/G nucleobases in DNA. [GRAPHICS] .
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    The use of different nanoparticles as carriers in gene silencing
    (Elsevier Science Bv, 2016) Tunali, Beste Cagdas; Turk, Mustafa
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