UC San Diego

Nanocarrier-based delivery systems can be used to increase the safety and efficacy of active ingredients in medical, veterinary or agricultural applications, particularly when such ingredients are unstable, sparingly soluble, or cause off-target effects. To this day, the majority of nanocarriers that are commercially available or in the development pipeline are spherical in shape. However, recent data suggests that high aspect ratio nanoparticles possess unique fluid transport properties (e.g. enhanced margination and tumor homing) and physiological interactions (e.g. decreased phagocytosis), which are advantageous for applications ranging from cancer treatment to pesticide delivery. Non-mammalian viruses are on the rise as economically and environmentally viable alternative to synthetic nanoparticles. Therefore I turned towards the study of high aspect ratio plant virus-based nanocarriers, and my dissertation focused on their translation in the fields of precision farming and nanomedicine. Specifically, I focused on the high aspect ratio viruses tobacco mosaic virus (TMV), and its U2 strain tobacco mild green mosaic virus (TMGMV). My initial studies evaluated TMGMV as a pesticide nanocarrier for the treatment of crops infected with endoparasitic nematodes. I report (1) the formulation and characterization of TMGMV loaded with large quantities of anthelmintic pesticides using non-covalent and covalent loading methods, (2) the bioavailability and treatment efficacy of the TMGMV nanopesticide vs nematodes in liquid cultures, (3) the superior soil mobility of TMGMV compared to free pesticides and other contemporary nanoparticle-based formulations, and (4) the successful development of non-infectious TMGMV particles for safe agricultural applications. In addition, I have applied the knowledge I have gained from my precision farming studies to the field of cancer nanomedicine. I developed a mathematical model to quantify diffusion and uptake of TMV in a spheroid system approximating a capillary-free segment of a solid tumor. I determined that TMV and TMGMV could be stably loaded with cationic photosensitizer drugs via non-covalent interactions for cancer photodynamic therapies. Lastly, I developed non-infectious cowpea mosaic virus formulation for its use as an in-situ cancer vaccine. Overall, my research enhanced the understanding of high aspect ratio viral nanoparticles and has laid groundwork toward their use as drug carriers for food safety and security as well as cancer treatment.