Medical Biotechnology Commons^™

Nanoparticles For Biomedical Applications, Joseph Kim

Dissertations and Theses (Open Access)

This thesis presents development and evaluation of the potential of three new nanoparticles for biomedical applications. With the rapid growth of the field of nanoscience, researchers have explored developing nanoparticles for various biomedical applications, including imaging, therapy, and drug delivery. This thesis demonstrates the development of two C­₆₀ fullerene based nanoparticles and one boron based nanoparticle to answer key questions related to their biological potential.

In the first part of the thesis, we describe synthesis and characterization of a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for …

Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel

Dissertations and Theses (Open Access)

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.

In …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Targeting Oncogenic Mirnas With Small Molecules For Breast Cancer Therapy, Paloma Del C. Monroig

Dissertations and Theses (Open Access)

The crucial role of microRNAs (miRNAs) in cancer pathobiology has driven the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, there is a need to develop screening strategies that can target tumors in a specific way. Small molecule inhibitors represent an attractive approach to pursue this. However, the absence of molecular structures for most of the miRNAs makes it very difficult to predict which inhibitors can bind to them. Herein we designed a strategy to screen for small molecules by assesing whether they could directly bind/ interact with miR-10b/miR-21. As part of our …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Tethered Il-15 To Augment The Therapeutic Potential Of T Cells Expressing Chimeric Antigen Receptor: Maintaining Memory Potential, Persistence, And Antitumor Activity, Lenka Hurton

Dissertations and Theses (Open Access)

Tethered IL-15 to augment the therapeutic potential of T cells expressing chimeric antigen receptor: Maintaining memory potential, persistence, and antitumor activity

Adoptive immunotherapy can retarget T cells to CD19, a tumor-associated antigen (TAA) expressed on B-cell malignancies, by the expression of a chimeric antigen receptor (CAR). Infusion of CAR-modified T cells for the treatment B-cell malignancies has demonstrated promise in preclinical and clinical trials. These data highlight the ability of infused CD19-specific T cells to be synchronously activated by large burdens of CD19⁺ leukemia and lymphoma. This can lead to dramatic antitumor effects, but also exposes the recipient to …

Development Of A Multi-Purpose Automated Synthesis Module For Production Of Novel Pet Radiopharmaceuticals, I Hong Shih

Dissertations and Theses (Open Access)

Among radiopharmaceuticals of positron emission tomography (PET), ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) made from commercialized automated synthesis module is the most frequently used in tumor diagnoses. But the false positive findings, such as infectious tissues and post-operative surgical conditions, show strong uptake of ¹⁸F-FDG in PET scans which requires extra clinical procedures to confirm the results. Moreover, the false negative findings, such as low glycolytic activity tumors, reduce the accuracy of PET scans. Therefore, there will be new PET radiopharmaceuticals to redeem the defects of ¹⁸FDG-PET applications.

Current commercialized automated synthesis modules are suitable for clinical use, but …

Development Of Hif-1Α/Hif-1Β Heterodimerization Inhibitors Using A Novel Bioluminescence Reporter Assay System For In Vitro High Throughput Screening And In Vivo Imaging, Yun-Chen Chiang

Dissertations and Theses (Open Access)

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study …

Improved Techniques For Acquisition And Analysis Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging For Detecting Vascular Permeability In The Central Nervous System, Cheukkai Hui

Dissertations and Theses (Open Access)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In …

Cellular Trafficking Of Single And Multistage Vectors, Silvia Ferrati

Dissertations and Theses (Open Access)

Nanomedicine is an innovative field of science which has recently generated many drug delivery platforms with exciting results. The great potential of these strategies rely on the unique characteristics of the devices at the nano-scale in terms of long time circulation in the blood stream, selective accumulation at the lesions sites, increased solubility in aqueous solutions, etc.

Herein we report on a new drug delivery system known as a multistage system which is comprised of non-spherical, mesoporous silicon particles loaded with second stage nanoparticles. The rationally designed particle shape, the possibility to modulate the surface properties and the degree of …