Browsing by Author "Kara, Goknur"

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Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy
(2019) Anilmis, Nur Merve; Kara, Goknur; Kilicay, Ebru; Hazer, Baki; Denkbas, Emir Baki; 31509450
In this study, the anticancer activities of two siRNA carriers were compared using a human lung adenocarcinoma epithelial cell line (A549). Firstly, poly(styrene)-graft-poly(linoleic acid) (PS-g-PLina) and poly(styrene)-graft-poly(linoleic acid)-graft-poly(ethylene glycol) (PS-g-PLina-g-PEG) graft copolymers were synthesized by free-radical polymerization. PS-PLina and PS-PLina-PEG nanoparticles (NPs) were prepared by solvent evaporation method and were then characterized. The size was found as 150 +/- 10 nm for PS-PLina and 184 +/- 6 nm for PS-PLina-PEG NPs. The NPs were functionalized with poly(l-lysine) (PLL) for c-myc siRNA conjugation. siRNA entrapment efficiencies were found in the range of 4-63% for PS-PLina-PLL and 6-42% for PS-PLina-PEG-PLL NPs. The short-term stability test was realised for 1 month. siRNA release profiles were also investigated. In vitro anticancer activity of siRNA-NPs was determined by MTT, flow cytometry, and fluorescence microscopy analyses. Obtained findings showed that both NPs systems were promising as siRNA delivery tool for lung cancer therapy.
Development of novel poly-l-lysine-modified sericin-coated superparamagnetic iron oxide nanoparticles as siRNA carrier
(2021) Kara, Goknur; Malekghasemi, Soheil; Ozpolat, Bulent; Denkbas, Emir Baki
Small interfering RNA (siRNA) is a promising therapeutic modality, however, its successful clinical application is still challenging due to the lack of safe and efficient carrier systems. Superparamagnetic iron oxide nanoparticles (SPIONs)-based drug or gene carrier systems have displayed tremendous promise in nanomedicine. They possess intrinsic unique superparamagnetism that provides them to be concentrated in the targeted therapeutic site of action where an external magnetic field is applied. SPIONs can be also designed as theranostic agents to achieve simultaneous therapeutic and diagnostic purposes. Despite these favorable features, SPIONs are colloidally unstable and can be easily eliminated in the circulation. More importantly, the toxicological concerns associated with SPIONs, which often lead to the generation of reactive oxygen species (ROS), need to be thoroughly considered. Various types of polymers have been proposed so far to cover the surface of SPION to overcome these disadvantages. Silk protein, sericin can be ideal as a coating material due to its high biocompatibility, good biodegradability, and in vivo stability. In terms of the development of SPIONs as siRNA carriers, to the best of our knowledge, no protein was used as the coating material, and SPIONs coated with sericin have not been reported in the literature as a drug or gene carrier system.
Magnetic Gelatin Nanoparticles As A Biocompatible Carrier System for Small Interfering RNA in Human Colorectal Cancer: Synthesis, Optimization, Characterization, and Cell Viability Studies
(2022) Selimovic, Amina; Kara, Goknur; Denkbas, Emir Baki
Iron oxide-based nanoparticles have gained tremendous attention in developing next-generation personalized medicine modalities. Gelatin can be a good alternative for encapsulating iron oxide nanoparticles with its biocompatibility, biodegradability, low immunogenicity, and richness of functional groups. Herein, magnetic iron oxide nanoparticles (MNPs) were synthesized, coated with gelatin (Gel-MNPs), and loaded with mammalian target of rapamycin (mTOR)-silencing siRNA to induce the in vitro therapeutic effect in colorectal cancer (CRC) cells. To the best of our knowledge, this study is the first report using Gel-MNPs as siRNA carriers. We first optimized several experimental conditions for the preparation of MNPs and Gel-MNPs and the resulting opti-mized nanoparticles showed a narrow size and size distribution. Gelatin-coating increased the storage stability by preventing the aggregation of MNPs and did not alter the magnetic characteristics of MNPs significantly. siRNA encapsulation abilities of Gel-MNPs were determined in the range of 18.4% and 41.5% in varying siRNA amounts. Bare Gel-MNPs were highly cytocompatible against CRC cells, Caco-2, while Gel-MNPs-mTOR-siRNA exhibited a significant anticancer effect to kill these cells. Comparison with HiPerFect, a commercial siRNA transfection reagent, demonstrated that Gel-MNPs-mTOR-siRNA inhibited cell viability almost similar to or better than HiPerFect-mTOR-siRNA. Taken together, our data indicated that Gel-MNPs could potentially be used in further gene silencing approaches as a safe and multifunctional siRNA carrier candidate.
Magnetically responsive, sorafenib loaded alginate microspheres for hepatocellular carcinoma treatment
(2020) Alpdemir, Sukran; Vural, Tayfun; Kara, Goknur; Bayram, Cem; Haberal, Erdem; Denkbas, Emir Baki; 0000-0003-2788-550X; 33010138; ABC-8833-2020
This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. Then, alginate-SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4 degrees C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate-SPION-sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.
MiR-329 mimic based nano-therapy inhibits growth and progression of triple negative breast cancer
(2020) Kara, Goknur; Kahraman, Nermin; Denkbas, Emir Baki; Calin, George; Ozpolat, Bulent
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.
Silencing of survivin and cyclin B1 through siRNA-loaded arginine modified calcium phosphate nanoparticles for non-small-cell lung cancer therapy
(2020) Kara, Goknur; Parlar, Ayhan; Cakmak, Melike Cokol; Coko, Murat; Denkbas, Emir Baki; Bakan, Feray; 32956996
With the development of nanotechnology, various drug delivery systems including inorganic nanoparticles, liposomes, polymers, etc. have been developed over the past decade. Some of these nanoparticles are also forthcoming candidates for the successful delivery of small interfering RNA (siRNA) for targeted gene silencing. Upon its discovery, siRNA was perceived as a highly promising agent in the treatment of various diseases. However, it could not exhibit the expected clinical outcomes owing to the unfavorable challenges during delivery. One such challenge was identified as the lack of an effective carrier. Among the carriers, calcium phosphate (CaP) nanoparticles have attracted remarkable attention due to the superior biochemical properties and hold great promise for siRNA. It is well known that synthesis conditions influence the types of crystalline phases of CaPs as well as morphology. In this study, to address the influence of these parameters on the success of siRNA delivery, three different arginine (Arg) modified CaP nanoparticles having different chemical and morphological characteristics were synthesized as being the carriers of two specific siRNAs against survivin and cyclin B1. The functioning of CaP surfaces with Arg results in positive zeta potential on the surfaces. Functionalized nanoparticles have a higher loading capacity compared to unmodified particles, as they have a cationic surface that can be easily attached to negatively charged siRNAs. The gene silencing ability and the consequent in vitro antitumor activity of these CaP-Arg-siRNA complexes were investigated using A549 non-small-cell lung cancer cells. We found that high survivin and cyclin B1 expression is associated with worse survival in patients with lung cancer based on the Kaplan-Meier database. Considering the promoting role of survivin and cyclin B1 in cancer development and progression, CaP-Arg-siRNA mediated suppression of these genes resulted in a significant decrease in cell growth and induction of apoptosis. Our data suggest that all three CaP-Arg nanoparticles synthesized in this work can be used as safe and efficient nanocarriers for siRNA delivery, offering the opportunity to develop new therapeutic strategies for the treatment of lung cancer.