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Access Type

WSU Access

Date of Award

January 2016

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Physics and Astronomy

First Advisor

Ratna Naik

Second Advisor

Bhanu P. Jena

Abstract

In recent years, magnetic nanoparticles (MNPs), especially superparamagnetic Fe3O4nanoparticles, have attracted a great deal of attention because of their potential applications in biomedicine. Among the other applications, Magnetic hyperthermia (MHT), where localized heating is generated by means of relaxation processes in MNPs when subjected to a radio frequency magnetic field, has a great potential as a non-invasive cancer therapy treatment. Specific absorption rate (SAR), which measures the efficiency of heat generation, depends on magnetic properties of the particles such as saturation magnetization (Ms), magnetic anisotropy (K), particle size distribution, magnetic dipolar interactions, and the rheological properties of the target medium.We have investigated MHT in two Fe3O4 ferrofluids prepared by co-precipitation (CP) and hydrothermal (HT) synthesis methods showing similar physical particle size distribution and Ms, but very different SAR ~ 110 W/g and ~ 40 W/g at room temperature. This observed reduction in SAR has been explained by taking the dipolar interactions into account using the so called T* model. Our analysis reveals that HT ferrofluid shows an order of magnitude higher effective dipolar interaction and a wider distribution of magnetic core size of MNPs compared to that of CP ferrofluid.

We have studied dextran coated Gd-doped Fe3O4 nanoparticles as a potential candidate in theronostics for multimodal contrast imaging and cancer treatment by hyperthermia. The effect of surfactant on the MHT efficiency and cytotoxicity on human pancreatic cancer cells was explored as well. Though further in vivo study is necessary in the future, these results imply that the dextran coated Fe3O4 dispersion could maintain their high heating capacity in physiological environments while citric acid coating require further surface modification to reduce the non-specific protein adsorption. We have also investigated the traffic, distribution, and cytotoxicity, associated with dextran functionalized FITC conjugated Fe3O4 nanoparticles, and our results demonstrate that there is a time-dependent distribution of these nanoparticles into different cellular compartments. Moreover, a novel conjugation of anti-cancer drug, Doxorubicin (Dox) with a labeling dye (FITC) onto dextran coated Fe3O4 nanoparticles was developed using existing EDC/NHS technique for specific drug targeting. The experiments on this unique drug-dye dual conjugation with human pancreatic cancer cell line (MIA PaCa-2) show that association of Dox onto the surface of nanoparticles enhances its penetration into the cancer cells as compared to the unconjugated drug while releasing Dox into the nucleus of the malignant cells.

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