Glioblastom Tedavisinde İleri Yaklaşım: Tümör Mikroçevresine Duyarlı ve Dual Etkili Nanopartiküler Sistemlerin Radyoterapinin Etkinliğini Artırmak İçin Tasarlanması ve Değerlendirilmesi

Abstract

Glioblastoma is one of the most aggressive brain tumors due to its features such as rapid proliferation and high invasion. Within the scope of this thesis study, in order to provide effective treatment of GBM by using radiotherapy and chemotherapy approaches together; Poly(lactic-co-glycolic acid (PLGA) nanoparticle formulations, targeted to the tumor with scFvEGFR, containing Perfluorocarbon to increase the effectiveness of radiotherapy, and loaded with PRP to prevent the repair of damage to GBM cells after radiotherapy, were designed, and their effectiveness on cell culture and tumor-developed experimental animals was evaluated. Solvent extraction and evaporation method was used to prepare talazoparib (TLZ) -containing methylcellulose nanocapsules (MSN) and PLGA nanoparticles. scFvEGFR was conjugated to PAA/EDC/NHS-coated, TLZ-loaded methylcellulose nanocapsule and tetradecafluorohexane-containing PLGA nanoparticle formulations, and the resulting formulations were prepared with a spherical structure and has been found to provide long-term release. It has been shown that the formulations have a certain level of cytotoxicity on cells in cell culture and that the targeting agent (scFvEGFR) increases the intracellular uptake in cell culture. In in vivo studies, the resulting formulation was shown to be effective in treating the GBM model in rats compared to other formulations and TLZ solution. This result was confirmed by the TUNEL method. A strong correlation was found between histopathological results and MRI results in the evaluation of tumor sizes. Biodistribution studies showed that the resulting formulation provided a higher rate of TLZ transport to the brain tissue compared to the TLZ solution.