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    The Novel 5-Fluorouracil Loaded Ruthenium-based Nanocarriers Enhanced Anticancer and Apoptotic Efficiency while Reducing Multidrug Resistance in Colorectal Cancer Cells
    (Springer/Plenum Publishers, 2023) Danisman-Kalindemirtas, Ferdane; Ozerkan, Dilsad; Kariper, Ishak Afsin; Bulut, Huri
    Recently, nanocarriers have been made to eliminate the disadvantages of chemotherapeutic agents by nanocarriers. Nanocarriers show their efficacy through their targeted and controlled release. In this study, 5-fluorouracil (5FU) was loaded into ruthenium (Ru)-based nanocarrier (5FU-RuNPs) for the first time to eliminate the disadvantages of 5FU, and its cytotoxic and apoptotic effects on HCT116 colorectal cancer cells were compared with free 5FU. 5FU-RuNPs with a size of approximately 100 nm showed a 2.61-fold higher cytotoxic effect compared to free 5FU. Apoptotic cells were detected by Hoechst/propidium iodide double staining, and the expression levels of BAX/Bcl-2 and p53 proteins, in which apoptosis occurred intrinsically, were revealed. In addition, 5FU-RuNPs was also found to reduce multidrug resistance (MDR) according to BCRP/ABCG2 gene expression levels. When all the results were evaluated, the fact that Ru-based nanocarriers alone did not cause cytotoxicity proved that they were ideal nanocarriers. Moreover, 5FU-RuNPs did not show any significant effect on the cell viability of normal human epithelial cell lines BEAS-2B. Consequently, the 5FU-RuNPs synthesized for the first time may be ideal candidates for cancer treatment because they can minimize the potential drawbacks of free 5FU.
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    Synthesis and Anticancerogenic Effect of New Generation Ruthenium-Based Nanoparticle from Homalothecium sericeum with Eco-Friendly Method
    (Springer, 2023) Samir, Nourhan; Ozerkan, Dilsad; Danisman-Kalindemirtas, Ferdane; Kariper, Ishak Afsin; Bulut, Huri; Kuruca, Duerdane Serap; Altuner, Ergin Murat
    BackgroundGreen synthesis is a simple, inexpensive, and highly efficient method for the preparation of nanoparticles. In this study, ethanol extracts of Homalothecium sericeum (HOM) moss were used as reducing agents for the synthesis of biocompatible ruthenium nanoparticles (RuNPs). The ruthenium-based green synthesis method has not been used in any other work in the literature. UV-visible spectrophotometer (UV-Vis), Zetasizer, FTIR, and EDX-SEM were used to characterize the RuNPs synthesized by the green synthesis method, and their efficacy on cell viability was tested on HCT116 human colon cancer cells.MethodsUV spectroscopic measurements were used to study the release of HOM-RuNPs. Apoptosis was assessed by measuring protein expression of p53, Bax, and Bcl-2 by Western blotting. The presence of apoptosis was confirmed by double staining with Hoechst dye/propidium iodide under a fluorescence microscope. HOM-RuNPs were also tested for BCRP/ABCG2 expression to check for drug resistance.ResultsHOM-RuNPs with a size of 70-80 nm were found to be most effective at a dosage of 5.71 mu g/ml and induced cell death by increasing the ratio of Bax/Bcl-2 and p53 expression. It was also shown to reduce multidrug resistance protein (ABCG2), suggesting that it may be useful against multidrug resistance.ConclusionRuthenium-based nanoparticles synthesized by a green synthesis technique may be a candidate for anticancer drugs in the pharmaceutical industry and deserve further attention for proof-of-concept studies.