Nanoparticles have the potential to revolutionize medicine, but many obstacles complicate the translation of nanoparticles from the bench to the clinic. A deeper understanding of nanoparticle synthesis parameters that influence nanoparticle size, drug loading, and surface chemistry is needed to accelerate the design of efficacious therapeutic nanoparticle systems. In this work, organic and inorganic nanoparticles were prepared with hydrodynamic diameters below 200 nm for applications in cancer treatment and immunology. Hydrophobic ion pairing was applied to enhance the loading capacity of drugs and peptides in polyester and polysaccharide nanoparticles systems. Polyester nanoparticles were successfully functionalized with streptavidin-Cy3, interferon gamma (IFN-γ), and CX3CL1. Poly(methacrylic acid), chitosan, and polyinosinic-polycytidylic acid (poly(I:C)) were successfully adsorbed to the surfaces of nanoparticles to enhance particle stability and targeting. Iron-based coupling media capable of eliminating ~ 90% of the water signal from an acoustic coupling bath during gradient echo magnetic resonance imaging (MRI) thermometry was successfully designed using magnetic iron oxide nanoparticles to improve the clinical efficacy of MRI-guided focused ultrasound surgery (MRI-FUS). While the critical nanoparticle design criteria may change depending on the biomedical application, fundamental concepts of nanoparticle design and synthesis can be applied across applications. The projects presented here help to bridge the knowledge gap regarding the use of flash nanoprecipitation (FNP) for nanoparticle synthesis. FNP is a scalable nanoparticle fabrication method that produces small, well-defined nanoparticle populations through rapid, turbulent mixing of multiple solvent streams. This work elucidates nanoparticle design concepts that can be applied across a wide variety of biomedical applications. / Doctor of Philosophy / Cancer remains a critical public health issue worldwide because many promising therapies never make it from the lab into the hospital. Many chemotherapeutic drugs are hindered by poor solubility and serious, undesirable side effects. In the past few decades, new production techniques have been developed to create carriers for these drugs to help overcome these obstacles. These carriers can be made from a variety of materials including metals and biodegradable polymers. In fact, it is even possible to create "smart" carriers that react to their environment to travel within the body or release the drugs they contain. Understanding how to design these carriers for different biomedical applications is critical. This work shows how carriers made from metal or polymer can be designed to exhibit desirable characteristics for use in biomedical applications ranging from vaccines to cancer treatment. Various ways to modify the surfaces of these carriers to tailor them for different applications are presented. This work provides valuable information that can help drive the next generation of biomedical innovation.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/113824 |
| Date | 13 February 2023 |
| Creators | Fergusson, Austin D. |
| Contributors | Graduate School, Davis, Richey M., Riffle, Judy S., Dervisis, Nikolaos G., Allen, Irving C. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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