Fabrication of multi-component superparamagnetic nanoparticles and magnetic heating performance for hyperthermia cancer therapy

Abstract

Nowadays, cancer has become a major public health problem worldwide. It is known that 19.3 million new cancer cases and approximately 10 million cancer deaths occurred worldwide in 2020 alone. The TUIK 2020 report, the cancer is in second place with 80,186 people in Turkey ranking of causes of death. Traditional methods such as chemotherapy, radiotherapy and surgery do not give highly successful results in cancer stages that have spread in the body. These treatment methods carry fatal risks by damaging healthy tissues depending on the treatment method in the patient. For this reason, various treatment methods have been developed that are expected to affect only damaged tissue. Hyperthermia is one of the methods developed for this purpose. Multilayer functional superparamagnetic nanoparticles (NPs) are used in the method, which can be used in medical imaging and treatment applications. With these NPs, it is tried to develop the use of optical and magnetic methods for both diagnosis and treatment of cancer. Thanks to a dielectric shell coated on the NPs, its agglomeration can be prevented, and thanks to an organic shell coated on it, its properties such as biocompatibility and stability can be increased, as well as various molecule adhesion capabilities for treatment purposes can be given to the surfaces of the NPs. In addition to the magnetic properties of these NPs, it will be possible to heat them with the near infrared (NIR) laser to be applied due to their surface plasmon resonance properties. Basically in this method; It is aimed to; (a) reach the denaturation temperature (42ºC) of the cancer cells by applying an alternative magnetic field that will affect only the tumor area, and (b) the malignant cells are destroyed by heating while the other healthy tissues remain stable. In this way, the side effects that occur in traditional methods are tried to be minimized. The two most important factors determining the use of magnetic NPs in hyperthermia therapy are; (a) the applied NPs must have a high ability to heat the cancerous tissue to the desired temperature and (b) heating should be limited only to the cancerous tissue. These two factors can be achieved by having excellent magnetic properties that can reach the target temperature by using a small amount of NPs in the target tissue. For this reason, the type of magnetic NPs used and their magnetic heating performance are of great importance. Studies on various NPs such as Fe3O4, MnFe2O4 are quite common, but it becomes impossible to compare the experimental results due to the different methods and different environmental conditions determined for NPs fabrication in the studies. Therefore, more research is needed to make hyperthermia treatment available. In the thesis, in the first part, Fe3O4, MgFe2O4, MnFe2O4 and SrFe12O19 NPs were synthesiszed as cores. Later, their outher surface was first coated with SiO2 layer, functionalized with amination, then decorated via Au NPs and consequently the outer surface of overall NPs will be coated via PEG. After each coating, the NPs have been characterized using FTIR, SEM and EDX. Heating process was carried out under AMF, using induction generator, in water and in agar according to the rate calculation of 0.1% (v/m) of the produced NPs. According to the results of the heating tests, among all samples, SrFe12O19 NPs showed the lowest and MgFe2O4 NPs showed the highest heating performance among all samples in the tests where different core types were compared. According to the heating results comparing the different coating stages, the aminated NPs gave the fastest warming result among the other coating stages. Comparing different coating steps, PEG coated samples gave the slowest heating result in the heating results. In addition, the heating performance of gold-coated samples, which is the previous coating step from PEG, is very close to that of PEG coated samples and gave the second lowest performance. As a result, our study has shown that different coating stages and NPs differences change the heating performance of superparamagnetic NPs. Although there are many studies of magnetic NPs in the literature, the effects of different types of magnetic NPs on the heating performance of different coating stages of these NPs were compared under standardized laboratory conditions. It is possible to say that this study, which is carried out with easily accessible and economical laboratory materials, is illuminating for future researches related to the subject.