Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
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Item Bio-Derived Microscale Containers for Disease Treatment and Diagnostics(2017) Liu, James; Raghavan, Srinivasa R; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Micro-erythrosomes (mERs) are microscale containers (3 to 5 µm in diameter) derived from red blood cells (RBCs, also called erythrocytes). They are prepared by removing hemoglobin from RBCs and resuspending the empty structures in buffer. In this work, we focus on adding new functionalities to mERs, with both therapeutics and diagnostics in mind. In our main study, we demonstrate the use of mERs as “Killer Cells” to attack cancer. mERs are loaded with the enzyme glucose oxidase (GOx) and then incubated in vitro with a strain of head and neck cancer cells (15B). In the presence of glucose from external media, the Killer Cells generate hydrogen peroxide (H2O2). H2O2 is a reactive oxygen species (ROS) which induces the cancer cells to undergo apoptosis (programmed cell death). We find a reduction in 15B cell viability of over 80%. In ancillary studies, we explore strategies for the long-term retention of solutes in mERS. Specifically, the cationic biopolymer chitosan is adsorbed to the surfaces of mERs, and the anionic biopolymer alginate is encapsulated in their cores. Both strategies are able to extend the diffusion time for loaded solutes. Additionally, we have attempted to adapt mERs for use as MRI contrast agents by incorporating lipids containing gadolinium into the membrane. These studies lay the foundation for many mER applications and demonstrate their versatility.Item Generating memory cytotoxic T lymphocytes through repetitive peptide boosting(2012) Smyth, Kendra; Xiao, Zhengguo; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cytotoxic T lymphocytes (CTLs) play a critical role in controlling intracellular pathogens and cancer cells, and induction of memory CTLs holds promise for developing effective vaccines against critical virus infections. However, generating memory CTLs remains a major challenge for conventional vector-based, prime-boost vaccinations. Thus, it is imperative that we explore nonconventional alternatives, such as boosting without vectors. We show here that repetitive intravenous boosting with peptide and adjuvant generates memory CD8 T cells of sufficient quality and quantity to protect against infection in mice. The resulting memory CTLs possess a unique and long-lasting effector memory phenotype, characterized by decreased interferon-gamma but increased granzyme B production. These results are independent of the specific adjuvant applied and are observed in both transgenic and endogenous models. Overall, our findings have important implications for future vaccine development, as they suggest that intravenous peptide boosting with adjuvant following priming can induce long-term functional memory CTLs.Item Synthesis of Magnetic Nanotubes as Magnetic Resonance Contrast Agents and Drug Carriers and the Study of Their Cytotoxicity(2008-11-20) Bai, Xia; Lee, Sang Bok; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)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.