Synthesis of Magnetic Nanotubes as Magnetic Resonance Contrast Agents and Drug Carriers and the Study of Their Cytotoxicity
Lee, Sang Bok
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The increasing interest in the medical application of nanotechnology has heightened the need for synthesizing nanoparticles with well-defined dimensions and multifunctionalities. Studies on template synthesis demonstrate relatively reliable reproducibility of the nanostructures. Moreover, differential modification can be achieved with template synthesis method. Based on template synthesis method, magnetic nanotubes (MNT), silica nanotubes (SNT) loaded with superparamagnetic iron oxide nanoparticles (SPION), were successfully prepared. The magnetic properties of MNTs including saturation magnetization (Msat) and magnetic resonance (MR) relaxivities were investigated. Results revealed that Msat of MNTs is as high as 95 emu/gFe, which is on the highest side of reported value for magnetite nanoparticles. The MR study showed that MNTs enhanced proton MR relaxation considerably, especially transverse relaxation T2 (*). The transverse relaxivities (r2(*)) of MNTs are higher than that of Feridex, a FDA approved MR contrast agent, indicating that MNTs could potentially act as efficacious T2(*)-weighted MR contrast agents. MNTs were also studied as drug carriers to control the loading and release of Doxorubicin (Dox: a cancer drug model). The inner surfaces of MNTs were modified with C18- and pyridine-silane with various ratios. The results showed that Dox molecules held in the MNTs were stable at pH 7.2, and released at pH 4.5. With proper modification, MNTs can be used to control drug release profiles. The magnetic nanoparticles in MNTs helped in loading drug molecules due to barrier effect. Cytotoxicity and cellular uptake of SNTs with two different sizes and surface charges were investigated for two cell models, primary (non-malignant) and cancer cells. The nanotubes showed limited toxicity which was concentration-, surface charge-, and length- dependent. The internalization was confirmed with both confocal microscopy and TEM studies. Confocal microscopic images demonstrated that endocytosis was one of the main mechanisms for internalization of nanotubes. A novel method was developed in this thesis to improve multifunctionality of SNT as a drug delivery system by modifying the nanotubes segmentedly between the entrance and the remainder. Ideally, we can make a universal delivery vehicle with SNTs as the constitute structure which can be filled with therapeutic and imaging payloads and have biological surface modifiers for targeting.