Magnetic nanoparticles have recently attracted much attention for potential biomedical applications such as targeted drug delivery, magnetic resonance imaging contrast agents and hyperthermia treatment of cancerous cells. Future research on biomedical applications also includes use of magnetic nanoparticles for cell and DNA separation. By functionalizing magnetic nanoparticles with cells or DNA selective biomolecules, the particles attach to the target and are removed from the sample upon passing through magnetic field gradients. The field gradients apply a force that attracts the particles given by the equation F = ∇(m · B), where m is the magnetization of the MNP, and B is the applied magnetic field. This type of magnetic manipulation is potential for in vivo applications such as targeted drug delivery, magnetic resonance imaging contrast enhancement and hyperthermia treatment of cancer. The magnitude of the field gradients of magnetic nanoparticles are significantly reduced due to the inverse square law dependence of magnetic field strength and subsequently the forces set up are reduced.
Although the research in this field has focused primarily on iron oxide nanoparticles, these oxide nanoparticles have a low magnetization that renders them ineffective, at the distances required for in vivo applications, due to the reduced forces felt by the nanoparticles. Successful implementation of such magnetic nanoparticles based system in vivo may require higher magnetization. The aim of this proposal is to synthesize high magnetization Fe-based MNPs functionalized with artificial proteins.
The research described in this dissertation focuses on synthesis, size control, structural and magnetic characterization and associated experimental studies to characterize their properties for application in magnetic fluid hyperthermia and magnetic resonance imaging applications. The method used for the synthesis of the Fe-based nanoparticles is the conventional borohydride reduction of the metal salt solution. Since our intention is to synthesize iron based nanoparticles we used iron salts such as FeCl3. A polymer such as polyethylene glycol is coated onto the oxide shell to make it biocompatible. Parameters such as length of the tube, diameter of the Y-tube junction and concentration of the reactants were varied to study the effect on particle size, structure and morphology of the magnetic nanoparticles.
X-ray diffraction measurements revealed that the particles typically contain three iron based phases such as a crystalline (α-Fe), nanocrystalline/amorphous (a-FeB/n-Fe) and Fe-oxide. By controlling the synthesis parameters such as length of the reaction tube, inner diameter of the Y-tube and concentration of the reagents the volume percentage of the three phases of the nanoparticles, viz. crystalline phase, amorphous phase and Fe-Oxide phases can be controlled effectively. The Fe-Oxide phase could not be determined whether is magnetite and maghemite phase because of the very broad nature of the peak. Transmission electron microscopy was used to study the particle size and the microstructural property of the samples. Samples with particle size in the range of 3 nm to 30 nm were fabricated. The magnetic properties of the nanoparticles studied were measured with a vibrating sample magnetometer with a maximum field of 1 Tesla. The particles magnetic properties such as magnetization and coercivity were typical of a soft ferromagnetic material with a high magnetization (in emu/g) and the coercivity was in range of 50 to 450 Oe.
The nanoparticles synthesized were used to study their performance in magnetic fluid hyperthermia and magnetic resonance imaging applications. In the hyperthermia, the power loss due to an alternating magnetic field had a direct correlation with the magnetization and the particle size of the nanoparticle. The power loss in magnetic fluid hyperthermia is an outcome from four loss mechanism, they are Brownian rotational loss, Neél's relaxational loss, hysteresis loss and eddy current loss. The Brownian rotation loss is the major contributor in monodispersed particle size while Neél's relaxational loss exist only in particle below 5 nm. The hysteresis loss is very small in superparamagnetic nanoparticles and increases with the particle size and predominantly exist in particles of all sizes; the eddy current loss in sub-nanometer particle very negligible when compared to the other major loss mechanism.
In magnetic resonance imaging contrast enhancement by estimating the spinlattice relaxation time (T1), spin-spin relaxation time (T 2) and spin-spin relaxation due to field inhomogeneity (T*2) the enhancement can be related to the particle size and magnetization. The contrast enhancement of the magnetic nanoparticle suspension in water, was responsible for shortening of the relaxation time of the proton in water. The contrast enhancement depends on the magnetization and the particle size of the magnetic nanoparticles.