Physical Sciences and Mathematics Commons^™

Mitochondria Imaging And Targeted Cancer Treatment, Tinghan Zhao

Dissertations

Mitochondria are essential organelles as the site of respiration in eukaryotic cells and are involved in many crucial functions in cell life. Dysfunction of mitochondrial metabolism and irregular morphology have been frequently found in human cancers. The capability of imaging mitochondria as well as regulating their microenvironment is important both scientifically and clinically. Mitochondria penetrating peptides (MPPs), certain peptides that are composed of cationic and hydrophobic amino acids, are good candidates for mitochondria targeting. Herein, a novel MPP, D-argine-phenylalanine-D-argine-phenylalanine-D-argine-phenylalanine-NH₂ (rFrFrF), is conjugated with a rhodamine-based fluorescent chromophore (TAMRA). The TAMRA-rFrFrF probe exhibits advantageous properties for long-term mitochondria tracking of …

Preparation Of Folic Acid-Carbon Dots-Doxorubicin Nanoparticles As Targeting Tumor Theranostics, Samson Dada

Electronic Theses and Dissertations

Carbon dots (CDs) have attracted much attention as an excellent gene/drug delivery and biological imaging agent for early cancer theranostics. In this study, we prepared two series of nanoparticles (NPs), which are composed of (CDs) with a targeting agent, folic acid (FA), and a chemotherapeutic agent Doxorubicin (Dox). All the NPs and their intermediates were characterized using ultraviolet-visible spectroscopy (UV-vis), fluorescence spectroscopy, and Fourier transform-infrared spectroscopy (FT-IR). The drug loading capacity (DLC) and drug loading efficiency (DLE) of two series of FA-CDs-Dox were assessed using UV-vis absorption spectroscopy at the wavelength of 485 nm. Both showed good DLE and DLC …

Elucidating The Mechanism Of Bone Morphogenetic Protein (Bmp) -Mediated Sox2 Downregulation In Ovarian Cancer, Zainab Motolani Shonibare

Theses and Dissertations

Sex determining region Y-box 2 (Sox2) is a transcription factor essential for maintaining self-renewal and pluripotency of undifferentiated embryonic stem cells. Sox2 is involved in multiple processes of cancer cells, however, regulation of Sox2 expression and the consequences of that regulation in cancer remains elusive. Previously, we demonstrated that BMP9/GDF2 is significantly reduced in expression in ovarian cancer (OVCA) cells, methylated in patient tumors and, promoted anoikis resistance in both breast and OVCA cell lines. In an attempt to identify genes downstream of BMP9 that may provide anoikis resistance, transcriptomics was performed leading to the identification of Sox2, a developmental …

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Theses & Dissertations

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be …

Development Of Novel Tumor-Targeted Compounds For Boron Neutron Capture Therapy, Micah John Luderer

Arts & Sciences Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) represents the most common primary brain tumor among adults. Despite surgical resection and aggressive chemoradiotherapy regimens, the current 2- and 5-year survival rates are only 27% and 9.8%, respectively. The low survival stems from the poor response to conventional therapy and underscores the critical need to develop new therapeutic approaches for GBM treatment. The high recurrence rate observed in GBM is in part attributed to the hypoxic (poorly oxygenated) tumor microenvironment. Hypoxic tumor conditions have been shown to increase metastasis, promote angiogenesis, and confer resistance to chemotherapy and radiation.

Hypoxic tissues are inherently radiation resistant due to …

Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox

Honors College Theses

While excessive cell death inevitably leads to negative effects, the endurance of damaged cells in the presence of death signals can be equally detrimental to health. Apoptosis, or programmed cell death, is a highly regulated process in which cues from within or from outside a cell can trigger an irreversible sequence of signals that carry out cell destruction known as the apoptotic cascade. A group of enzymes called caspases play a vital role in this cascade with some participating as initiators and others acting as effectors of protein cleavage and intracellular breakdown. Although it is normal for the activity of …

Design, Synthesis, Characterization And Anti-Cancer Effects Evaluation Of Interchain Cysteine Linked Antibody Drug Conjugates, Ke Li

Doctoral Dissertations

"Antibody drug conjugates (ADCs) are emerging therapeutic products specially designed for the treatment of cancers. Potent cytotoxic agents are linked to antibodies via linkers. Antibody drug conjugates, which take advantage of both antibodies and cytotoxic agents, showed high selectivity towards cancer cells. Cytotoxic agents are delivered to the cancer cells selectively and kill them from inside while leaving low or non-toxicity towards normal cells. Antibody drug conjugates are actually heterogeneous mixtures. The major heterogeneities mainly lie in the drug to antibody ratio (DAR) and drug linking positions, both of which potentially affect the therapeutic index of ADCs. In this research, …

Antitumor Properties Of Imidazolium Salts, Jenna Frantz

Williams Honors College, Honors Research Projects

This is the final write-up for an honors research project for the University of Akron Williams Honors College. Synthesis of novel imidazolium salts was conducted. Following synthesis of imidazolium salts, the stability of the compound was tested at 37°C over a 72-hour period to give preliminary information about drug stability in vivo. 2D NMR was also conducted to confirm the structure of TPP-1. The student wrote an experimental protocol for the use of C57BL/6 mice and performed the online CITI training by the IRB to prepare to work with animals in a study of the antitumor properties of imidazolium salts …

Killing Breast Cancer One Porphyrin At A Time, Taylor C. Lymburner

Honors Theses

New treatments for cancer are continuously being developed and improved. One such treatment is Photodynamic Therapy, more commonly referred to as PDT. PDT is quickly becoming more popular due to its relative lack of side effects that are present in other treatments. In PDT, light-sensitive agents are required and are activated by light in the targeted cells. There are many types of PDT agents but the one focused on in this research is a four-pyrrole ring structure known as a porphyrin. The combination of H2 TPPC with 3- amino-oxetane-3-yl-methanol created the final product ofH2TPP-Oxo-MeOH. Once the porphyrin was formed, it …