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Browsing by Subject "Supramolecular"

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    Optimizing Metal Complexes as Bacteria-Specific Tracers for in vivo Nuclear Molecular Imaging and Modulators of the Nuclease Resistance of DNA Nanostructures
    (2023-05) Joaqui Joaqui, Michel Andrey
    Infectious diseases caused by bacteria remain one of the major global threats to human health. Rapid and precise diagnosis is thus crucial for preventing the propagation of these bacterial pathogens and achieving favorable treatment results for impacted patients. To achieve this, diagnostic methods must possess the ability to accurately detect the bacterial pathogen with high selectivity, while also being prompt to facilitate rapid containment and informed treatment decisions. In vivo nuclear molecular imaging modalities such as PET and SPECT have gained importance as alternative diagnostics techniques, especially in scenarios where the site of infection is unknown, or the extraction of sample is anatomically challenging rendering well-established in vitro diagnostic techniques impractical. The effectiveness of these in vivo imaging techniques heavily relies on the utilization of proper radiolabeled probes that target bacteria. Currently, there are no radiotracers available that can be swiftly and easily prepared and that exhibit the necessary selectivity for bacterial cells to enable clear and definitive diagnosis. The first part of this dissertation presents an investigation regarding the use of artificial siderophore analogs of enterobactin, a bacterial virulence factor, as promising scaffolds for the development of metal-based radiopharmaceutical agents suitable for the detection of bacteria in vivo. The study covers the rationale behind the design of the artificial enterobactin analogs, the study of the in vitro and in vivo stability of the 68Ga and 45Ti-labeled enterobactin analogs, their suitability as nuclear imaging agents, as well as the evaluation of their abilities to image a bacterial infection in vivo.The second part of this dissertation, on the other hand, is dedicated to exploring the stability challenges faced by DNA nanotechnology in biologically relevant environments, particularly the instability of DNA-based nanomaterials. DNA nanostructures exhibit unique properties and hold great potential in areas such as biotechnology, nanoelectronics, and nanomedicine. However, these materials encounter numerous hurdles, such as degradation by nucleases and enzymes when introduced into biological environments like blood, tissues, or cells. Such degradation significantly impairs the stability and performance of DNA nanomaterials, curtailing their effectiveness in biological and biomedical applications. Hence, the field of DNA nanotechnology is currently grappling with the critical challenge of devising techniques to enhance the stability and performance of DNA nanomaterials under such conditions. The second section of this dissertation describes a methodical exploration of the modulation of the degradation of DNA nanocages through reversible supramolecular functionalization with metal complexes. The study encompasses the development and synthesis of several coordination compounds featuring metal centers such as EuIII, TbIII, PtII, CuII, CoII, and RuII, as well as a diversity of ligands. Further, the binding affinities of these metal complexes for DNA nanostructures are assessed, and their ability to mitigate the degradation of DNA nanostructures in biologically relevant media is evaluated.