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.

<p dir="ltr">Flash Nanoprecipitation (FNP) is a technique that allows organic nanocarriers (NCs) with core-shell architecture to be prepared reproducibly and at scale. The surface shell may be designed independently of the content in the core. This can allow for encapsulated active ingredients to be delivered to areas of the plant where they naturally would not move to but are needed, the biodistribution becoming a function of NC properties and release of active from the NC. The scalability of FNP is also attractive, since large scale production is ultimately required for commercialization of novel agrochemical solutions. In Chapter 3 scalable NCs encapsulating streptomycin (STP) have been prepared at high encapsulation efficiency (EE) and with controlled release of the antibiotic (< 5%). A surface-similar NC has been shown to translocate (~ 6%) to the roots of citrus trees under controlled conditions after foliar spraying. In vitro efficacy suggests that, if enough NCs containing STP are able to reach the phloem sections of trees where CLas resides at sufficient concentrations under field conditions, then this novel formulation may be able to offer an effective solution for managing the disease. Chapter 4 highlights the challenges in encapsulating weakly hydrophobic fungicides via FNP, the strategies that were employed to module fungicide solubility, and initial quantitative efforts to determine fungicide EE in a reliable and accurate manner. Even without full knowledge about the form in which a particular fungicide, mefentrifluconazole (MFZ), was present in the NCs that were applied to turfgrass during a greenhouse biodistribution test, the novel formulation provided higher MFZ recovery in the lower roots than the conventional treatment 7 days after application. It also presented sustained higher recovery of MFZ on the blades for up to 3 days and after blade clipping at 14 days. These results may indicate that MFZ was present in the vasculature.</p>