Glioblastomanın Görüntüleme ve Fotodinamik Tedavisi İçin Multifonksiyonel, Hedeflendirilmiş, Teranostik Lipozomların Geliştirilmesi ve Etkinliğinin İn Vitro İncelenmesi

Abstract

The desired success in the effective diagnosis and treatment of glioblastoma (GBM), which is one of the types with the highest incidence and lowest survival of brain tumors, has not yet been achieved and studies on effective and specific diagnostic and treatment agents have increased. Within the context of the thesis study, it was modified with N-acetyl glucosamine (NAG) to target GLUT1 for the diagnosis and treatment of GBM; 68Ga-labeled for PET/CT imaging, IR780-encapsulated for photodynamic/photothermal therapy (PDT/PTT) and NIR imaging, PEG-coated, nanosized neutral and positively charged theranostic liposomes have been developed and characterization, labeling efficiency, labeling stability, in vitro release profile and stability studies have been carried out. Cell uptake in RG2 and U87 cell line, NIR and fluorescence microscope images were taken in RG2 cell line and PDT/PTT activities were evaluated in NIR light (808 nm, 0.8-1 W/cm²). Their cytotoxicity was studied in RG2, U87, and L929 cell lines. Liposomes with optimum mean particle size (181-193 nm), encapsulation efficiency (79-84%), and zeta potential (-5 - -7 mV) showed release in accordance with Langenbucher kinetics. At pH: 3,5, 80oC and 5 min. maximum labeling efficiency was determined with 68Ga during the incubation period. It was determined that they remained stable for 30 days at 4oC and the intracellular uptake of targeted formulations was higher than non-targeted and positively charged formulations compared to neutral formulations. The formulations showed PDT/PTT activity under NIR light (808 nm, 0.8-1 W/cm²) and showed lower cytotoxicity in the L929 cell line than RG2 and U87. Targeted liposomes have been evaluated as potential theranostic agents for the treatment of GBM with PDT/PTT and PET/CT and NIR imaging in vitro.