Timokinon-bazlı Magnetolipozom ve Fitozom Nanopartiküllerinin Biyosentezlenmesi, Karakterizasyonu ve Glioblastoma Hücrelerinin Demir Metabolizmasına Etkilerinin Araştırılması

Abstract

Treatments for Glioblastoma (GB), a fatal brain tumor characterized by treatment resistance and relapses are inadequate. Therefore, in this study, in order to contribute to the treatment strategies targeting iron-based cell death, Magnetoliposome (Mag) nanoparticles (NP) to increase iron function in the cell and Phytosome NPs to reduce iron function in the cell were synthesized to test two opposing treatments in GB cells. Based on the chelating property of thymoquinone (TQ), TQ-FeNPs were first synthesized using the green method. Then, TQ-FeNPs were loaded into the prepared liposomes for acting as an active ingredient and MagNPs were created. Additionally, TQ-based FitNPs were prepared. The characterizations of the two NPs were performed. In U87-MG GB cells, the effects of NPs on on cytotoxicity, apoptosis, free radical and lipid peroxidation, as well as their iron chelating activities in the cells were examined. The functional band and binding properties (FT-IR) of TQ, Fe and phospholipid contents of NPs; their elemental structures and purities (EDX); their round-looking morphological structure (STEM); and <100nm sized of their, their homogeneously distributed (DLS/pdi) and the stable structures of their (zeta potential) were seen and they were confirmed to be NP. %EEs of NPs are 75%, their release characteristics are as first burst and then controlled release and their stabilities are medium were evaluated In GB cells, the IC50 dose of NPs was determined as 0.05mg/ml. In U87-MG cells, the dose-dependent effects of FitNPs on enhancing apoptosis, and their reducing effects on ROS and lipid peroxidation levels were attributed to the dominance of the antioxidant properties of TQ; additionally their reducing effects on iron activity would be low due to their less chelating activities were concluded. Since the fact that not being seen of effects of MagNPs on apoptosis, significantly high effects of their on ROS and lipid peroxidation levels, and significantly high of their chelator activities were thought that the MagNP-ferroptosis relationship should be elucidated in further studies because of predicted that the cytotoxic effects of their on GB cells may be through ferroptosis. As a result, it is a first because of not seen in the literature of NPs like TQFe-Mag. Additionaly it was throught that their cytotoxicicities seen in GB cells may be due to their chelator properties that increase iron activity at high levels. It was concluded that MagNPs are promising in terms of iron-chelator therapies, at the same time that further researcies are needed in the future in terms of both in such chelator treatments and that applications combined of iron-based diagnosis and treatment (theranostics)