Browsing by Author "Celik, Ekin"

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    Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system
    (2019) Celik, Ekin; Bayram, Cem; Denkbas, Emir Baki; 31147048
    Degenerative cartilage is the pathology of severe depletion of extracellular matrix components in articular cartilage. In diseases like osteoarthritis, misregulation of microRNAs contributes the pathology and collectively leads to disruption of the homeostasis. In this study chondroitin sulfate/hyaluronic acid/chitosan nanoparticles were prepared and successfully characterized chemically and morphologically. Results demonstrated higher chondroitin sulfate amounts led smaller nanoparticles, but lower surface zeta potential due to high electronegativity. After optimization of chondroitin sulfate amounts regarding size and charge, nanoparticles were loaded with microRNA-149-5p, a therapeutic miRNA downregulated in osteoarthritis, and evaluated focusing on their loading efficiency, release behaviour, cytotoxicity and gene transfection efficiency in vitro. Results showed all nanoparticle formulations were non-toxic and promising gene delivery agents, due to increased levels of microRNA-149-5p and decreased mRNA levels of microRNA's target, FUT-1. Highest gene transfection efficiency was obtained with the nanoparticle formulation which had the highest chondroitin sulfate load and smallest size. In addition, owing to their high chondroitin sulfate cargo, all nanoparticles were reported to enhance chondrogenesis, which was demonstrated by gene expression analysis and sulfated glycosaminoglycan (sGAG) staining. The obtained data suggest that the delivery of microRNA-149-5p via polysaccharide based carriers could achieve collaborative impact in cartilage regeneration and have a potential to enhance osteoarthritis treatment.
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    Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment
    (2019) Yalcin, Eda; Kara, Goknur; Celik, Ekin; Pinarli, Ferda Alpaslan; Saylam, Guleser; Sucularli, Ceren; Ozturk, Serhat; Yilmaz, Esin; Bayir, Omer; Korkmaz, Mehmet Hakan; Denkbas, Emir Baki; 31066619
    Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.