Nanomaterials and Polymers for Nitric Oxide Therapeutic Delivery and Sensing of Nitric Oxide Reservoir

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Copyright: Luo, Jeff
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Abstract
Nitric oxide (NO) plays pivotal roles in various physiological systems and has immense therapeutic potential. NO, however, has a short half-life (<5 s) and a short diffusion distance of ~160 μm in vivo, and its physiological functions are highly dependent on its concentrations. Current NO delivery strategies can be generally categorized into non-catalytic and catalytic (enzymatic) approaches. For the former, the longevity of the NO delivery systems principally relies on the finite NO donor reservoir, while the latter is limited by the low stability of natural enzymes. Another important challenge in NO delivery is the difficulty in accurately detecting circulating NO reservoir in blood. To address these challenges, this thesis focuses on the design, synthesis, and applications of nano-biomaterials to enable sustained NO delivery and accurate detection of endogenous circulating NO reservoir. This thesis revealed ceria nanoparticles as a new class of nanomaterials with the unique ability to catalyze NO generation from NO donors. The therapeutic activity of ceria-induced NO was demonstrated to inhibit cancer cell proliferation. This unique NO-generating feature stood in contrast to the well-established understanding of ceria to scavenge NO. This study provided deeper insights into the bio-functions of ceria nanoparticles and broadened their biomedical applications. Then this thesis reported the first catalytic polymers that generate NO, in particular amine-containing polymers, e.g., polyethyleneimine (PEI). These polymers can be easily integrated into a suite of biomaterials (e.g. hydrogels) to equip them with NO delivery capability. The therapeutic application of polymer-induced NO was demonstrated to prevent the formation of Pseudomonas aeruginosa biofilm. Finally, the thesis tackled the demand for rapid and accurate detection of human serum albumin (HSA, the most abundant circulating NO reservoir in blood) by developing a fluorescent paper-based sensor. This sensing platform allowed sensitive (detection limit of 0.91 g/L) and rapid (20 minutes) point-of-care detection of HSA and HSA-related disease diagnosis by visible color change, and could be extended to the detection of a spectrum of biomarkers. Collectively, these findings open new routes to produce next generation nano-biomaterials for the diverse biomedical applications of NO such as anticancer, antibacterial, and sensing applications.
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Publication Year
2022
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Thesis
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PhD Doctorate
UNSW Faculty