Date

2017

Author

Akpınar, Yeliz

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Over the past decade, there has been an increasing interest in using nanotechnology for cancer therapy. Magnetic-based systems containing magnetic nanoparticles have gained popularity because of their unique ability to be used in magnetic resonance imaging, magnetic targeting, drug carrying and hyperthermia. The last one represents a novel therapeutic concept to cancer treatmentIn biomedical and clinical applications the most commonly used magnetic nanomaterials are the iron oxide nanoparticles. Current progress in the synthesis of iron oxide nanoparticles with different shapes (flower, cube, spherical) and compositions show that the heating power of the magnetic material can be optimized for hyperthermia. Compared to the therapy of using chemotherapeutic agents or molecular-targeting therapeutic agents, an alternative antitumor approach can be proposed by considering tumor metabolism. The reason cancer is so fast growing is that the mitochondria have been deactivated, so the cells avoid apoptosis, as well as being able to grow in the absence of oxygen (glycolysis). Dichloroacetate (DCA) which is a pyruvate dehydrogenase kinase inhibitor, reverses this process, induces apoptosis, decreases proliferation, and inhibits tumor growth. However, therapeutically prohibitive high DCA doses are needed for tumor growth suppression. Thus, preparation of magnetic nanoparticles designed to carry pharmacologically relevant doses of DCA directly to the tumor site and enhance its effective cellular uptake may represent a more effective therapeutic option. In this study, flower, cubic and spherical shaped iron oxide nanoparticles, having high heating power that can be used in hyperthermia application were prepared. For inductive heating of magnetic nanoparticles, an induction device was designed. Hyperthermia studies was started by using spherical iron oxide nanoparticles. The surface of nanoparticles prepared was modified with heparin, a natural polymer and DKA was embedded into heparin layer. However, for effectively targeting mitochondria, triphenylphosphonium cation was incorporated to DKA through a biodegradable amide linkage before loading on to the nanoparticle. Finally nanoparticles was conjugated to 2-deoxy-D-glucose (2-DG) in order to transport the particles into the cells via glucose transformers present on the cell membranes. It needs to be stated that, besides DKA and hyperthermia, both heparin and 2-DG are known to play role in apoptosis process. Therefore these novel nanoparticles are expected to deliver their cargo directly to cancer cell and cause a cell death via apoptosis. The binding and uptake of nanoparticles, cytotoxicity and apoptosis were investigated using liver cancer cell line (HepG2). It is known that iron oxide nanoparticles are used as a contrast reagent in MRI systems. Consequently, these nanoparticles were also useful for monitoring the outcomes of the medical treatment by magnetic resonance imaging, MRI.

Subject Keywords

Cancer., Heparin., Ferric oxide., Nanoparticles.

URI

http://etd.lib.metu.edu.tr/upload/12621427/index.pdf
https://hdl.handle.net/11511/26952

Collections

Graduate School of Natural and Applied Sciences, Thesis