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Öğe Effects of radiofrequency exposure on in vitro blood-brain barrier permeability in the presence of magnetic nanoparticles(Academic Press Inc Elsevier Science, 2022) Şentürk, Fatih; Çakmak, Soner; Koçum, İsmail Cengiz; Gümüşderelioğlu, Menemse; Öztürk, Göknur GülerThe blood-brain barrier (BBB) remains a major obstacle for the delivery of drugs in the treatment of many neurological diseases. In this study, we aimed to investigate the effects of radiofrequency electromagnetic fields (RF-EMFs) on the permeability of an in vitro BBB model under RF exposure alone, or in the presence of nanoparticles (NPs). For this purpose, an in vitro BBB model was established by seeding human umbilical vein endothelial cells (HUVECs) and human glioblastoma cell line (T98G) on the apical and basolateral sides of the transwell membrane, respectively. The integrity of the BBB model was confirmed by measuring transendothelial electrical resistance (TEER), and a fluorescein isothiocyanate (FITC)-dextran permeability assay was performed when the resistance reached 120 U cm(2). After the RFfield exposure (13.56 MHz, 80 W, 10 min), we found that FITC-dextran transported across the in vitro BBB was increased 10-fold compared to FITC-dextran transported without an RF-field. This notable phenomenon, which can be called the burst permeability RF effect (BP-RF), has been proposed for the first time in the literature. Subsequently, the effect of the RF-field on BBB permeability was also investigated in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) and magnetic poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (m-PNPs). It was found that the amount of both transported NPs on the basolateral sides increased after exposure to the RF-field. As a result, the RFfield can be applied simultaneously during treatment with clinical agents or nanocarriers, improving the permeability of the BBB, which may contribute to therapeutic efficacy of many drugs that are used in neurological diseases. (c) 2022 Elsevier Inc. All rights reserved.Öğe Hydrolytic instability and low-loading levels of temozolomide to magnetic PLGA nanoparticles remain challenging against glioblastoma therapy(Elsevier, 2022) Şentürk, Fatih; Çakmak, Soner; Gümüşderelioğlu, Menemse; Öztürk, Göknur GülerTemozolomide (TMZ) is the first-line chemotherapeutic agent for the treatment of newly diagnosed glioblastoma (GBM). However, chemoresistance, hydrolytic instability, and insufficient drug accumulation are major challenges limiting the effectiveness of TMZ chemotherapy. Although various nanocarriers have been offered to overcome these limitations, there are some discrepancies regarding the TMZ encapsulation efficiency (EE%). In this study, by examining the behavior of TMZ in different solvents, we aimed to confirm the loading efficiency of TMZ in the nanoparticles (NPs) and investigate the therapeutic efficacy of TMZ-loaded NPs in human GBM cell line (T98G). For this purpose, firstly, we investigated the stability of TMZ and its degradation product (AIC) to evaluate whether TMZ degradation affects the measured EE% from the supernatant (indirect method) or the NPs (direct method). Subsequently, we tried to load TMZ into magnetic poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (TMZ-m-PNPs) by modifying the synthesis parameters in a controlled manner. It was concluded that the indirect method might cause misleading results due to the high hydrolytic instability of TMZ during the NPs synthesis or washing steps. Although many modifications have been performed in the synthesis method, the EE% of TMZ ranged between 1% and 7%. In cell culture, IC50 values of free-TMZ were found for human endothelial cells (HUVEC, similar to 500 mu M) and human glioblastoma cells (T98G, similar to 350 mu M) at the 72nd h. Furthermore, cell viability was quantified using MTT, live/dead cell viability, and Annexin V-FITC/PI assays of TMZ-m-PNPs, but cytotoxicity of NPs was not dose-dependent in T98G cells. Overall, this study offers two major new insights; first, the EE% of TMZ in NPs should be determined by the direct method; second, to increase the therapeutic efficacy of TMZ-loaded NPs on GBM cells, it may be recommended not to use the PLGA-based nanocarrier system that may contribute to poor therapeutic response.Öğe Hyperthermia Efficacy of PEGylated-PLGA Coated Monodisperse Iron Oxide Nanoparticles(2023) Şentürk, FatihMagnetic nano hyperthermia (MNH) is a promising technique for the treatment of a variety of malignancies. This non-invasive technique employs magnetic nanoparticles and alternating magnetic fields to generate local heat at the tumor location, which activates cell death pathways. However, the efficacy of MNH is dependent on the physicochemical properties of the magnetic nanoparticles, such as size, size distribution, magnetic properties, biocompatibility, and dispersibility in the medium. In this study, it is aimed to evaluate the heating capacity of poly (lactic-co-glycolic acid)-poly (ethylene glycol) di-block copolymer (PLGA-b-PEG) coated monodisperse iron oxide nanoparticles (IONs) as an effective mediator for MNH application. For this purpose, monodisperse IONs with a narrow size distribution and a mean particle size of 8.6 nm have been synthesized via the thermal decomposition method. The resulting IONs were then coated with the PEGylated-PLGA polymer and homogeneously dispersed in the polymeric matrix, which had a clearly defined spherical shape. Additionally, the specific absorption rate (SAR), reflecting the amount of heat dissipation from the NPs to the surrounding medium, was calculated for different concentrations (10, 5, 2.5, and 1.25 mg/mL) of PEGylated-PLGA-IONs. At 5 mg/mL PEGylated-PLGA-IONs (125 ?gFe/mL) were found to have a maximum SAR value of 313 W/g. In conclusion, the homogenous dispersion of IONs in PEGylated-PLGA matrix may be one of the critical parameters to enhance the SAR value for MNH-based cancer therapy.
