THERMAL AND MECHANICAL MANIPULATION OF IRON OXIDE NANOPARTICLES FOR TARGETED DRUG/GENE DELIVERY AND THERAPEUTICS
Merve Zuvin
Mechatronics Engineering, PhD Dissertation, 2019
Thesis Jury
Prof. Dr. Ali Koşar (Thesis Advisor), Prof. Dr. Devrim Gözüaçık, Prof. Dr. Kürşat Şendur, Assoc. Prof. Dr. Havva Yağcı Acar, Assist. Prof. Dr. Yegan Erdem
Date & Time: 4th, January 2019 – 11.00 AM
Place: Collaboration Space IC
Keywords : Hyperthermia, induction heating, breast cancer, superparamagnetic iron oxide nanoparticles, magnetic actuation, magnetofection
Abstract
Superparamagnetic iron oxide nanoparticles provide a platform to deliver therapeutic agents to any desired group of cells in a safe fashion. These particles can be manipulated by externally applied magnetic fields, targeted to specific tissues and heated in focused fields for cancer treatment. Hyperthermia performance of SPIONs depends on the magnetic field strength as well as the field frequency. A part of this dissertation displays the therapeutic effect of Poly(acrylic acid)-coated, anti-HER2-tagged SPIONs on breast cancer cells using a low magnetic field strength of 0.8 kAm-1, which is significantly lower compared to the literature, with a frequency of 400 kHz. HER2-positive SKBR3 and MDA-MB-453 cell lines successfully internalized the nanoparticles. The particles, which were not toxic to these cell lines, led to a prominent decrease in cell proliferation and survival in MDA-MB-453 cells when subjected to hyperthermia.
Gene therapy is another developing method for the treatment of various diseases. A strong alternative is magnetofection, which involves the use of SPIONs and external magnetic field to enhance the localization of SPIONs at the target site. A new magnetic actuation system consisting of four rare earth magnets on a rotary table was designed and manufactured to have improved magnetofection. The actuation effect was revealed with green fluorescent protein DNA bearing-nanoparticle transfection to MCF7 cells. The applied magnetic field in this system increased the transfection efficiency and viability relative to traditional transfection methods. At the same time, it also reduced the transfection time (down to 1 hour) of the standard polyethylenimine transfection protocol.