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    GRGDS-conjugated and curcumin-loaded magnetic polymeric nanoparticles for the hyperthermia treatment of glioblastoma cells
    (Elsevier, 2021) Senturk, Fatih; Cakmak, Soner; Kocum, Ismail Cengiz; Gumusderelioglu, Menemse; Ozturk, Goknur Guler
    Thermally responsive and ligand-mediated drug delivery systems have the potential to improve the treatment of brain tumors, especially, most lethal one, glioblastoma multiform (GBM). Magnetic nanoparticle-mediated hyperthermia becomes one of the most promising alternative therapy for GBM treatment in cases where localized heating and targeted delivery of a therapeutic drug can be achieved on the tumor site. In this study, it is aimed to increase the therapeutic efficiency of multi-functionalized nanoparticles (NPs) in combination with radiofrequency hyperthermia (RF-HT) on GBM cells. For this purpose, firstly, a low-cost and portable home-built RFHT system suitable for in vitro/in vivo studies was successfully implemented and tested at 13.56 MHz frequency with power up to approximately 400 W. Subsequently, the highly monodispersed superparamagnetic iron oxide nanoparticles (SPIONs), which could interact with the RF magnetic field, were synthesized with the mean particle size of 5.6 +/- 0.9 nm. The obtained SPIONs were coated with poly (lactic-co-glycolic acid)-poly (ethylene glycol) di-block copolymer (PLGA-b-PEG). Most of the SPIONs were uniformly distributed in such a well-defined spherical-shaped polymeric NP. Moreover, curcumin (Cur), a potential agent for GBM treatment, was loaded into the magnetic polymeric nanoparticles (m-PNPs) with a loading capacity of 8% (w/w, Cur/NPs) and a mean diameter of Cur-loaded m-PNPs (Cur-m-PNPs) was 142 +/- 70 nm. To increase cellular uptake and targeting ability of NPs, glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide was immobilized on the Cur-m-PNPs and the amount of GRGDS was detected as 37 mu g/mg NPs. In vitro cytotoxicity studies revealed that the presence of GRGDS on Cur-m-PNPs (GRGDS-Cur-m-PNPs) improved the cytotoxic efficiency of Cur-m-PNPs by 6-fold in GBM-cells for all incubation times (24, 48 and 72 h). Furthermore, NPs with RF treatment exhibited higher antitumor activity than that of NPs without RF on GBM cells. This result may be attributed to the thermal (SPIONs) or non thermal (cellular membrane) effects or both of them on cells. Overall, this study showed that RF-HT in combination with GRGDS-Cur-m-PNPs could provide a feasible approach to improve GBM treatment.
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    Stepwise implementation of a low-cost and portable radiofrequency hyperthermia system for in vitro/in vivo cancer studies
    (Taylor & Francis Inc, 2021) Senturk, Fatih; Kocum, I. Cengiz; Ozturk, Goknur Guler
    In recent years, interactions of radiofrequency (RF) electromagnetic fields with biological tissue have become one of the most promising strategies for noninvasive cancer hyperthermia treatment. Despite the growing interest, there has been a scarcity of studies involving the detailed construction of a complete RF-hyperthermia (RF-HT) system. Here a low-cost and high-power RF-HT system is reported with a specific frequency which can be used in biological samples. A laboratory-constructed RF-HT system composed of a radiofrequency oscillator, radiofrequency driver, radiofrequency amplifier, radiofrequency matching network, and an induction coil applicator were constructed and characterized by a stepwise approach. Although the RF driver and amplifier were purchased as professionally designed kits, significant modifications were required for these components. The results showed that the RF-HT system was successfully constructed and tested at 13.56 MHz with a power as high as 400 W. As a preliminary biological experiment, cell culture medium exhibited an approximate 3 degrees C increase in temperature induced by the RF-HT device at 250 W for 10 min. Moreover, the developed system is suitable drug targeting, drug release, and cellular uptake and designed to be cost-effective for in vitro/in vivo studies involving cancer therapy.