UC San Diego

The study and implementation of nanotechnology as applied to biology is making substantial progress toward the expansion of the dialogue between synthetic and biological systems. This dialogue leads to a deeper understanding of the origins, manifestations, and characteristics of biological phenomenon that ultimately will lead to improved methods of diagnosing and treating a variety of pathologies. Perhaps the most prevalent application of this new technology is in the field of cancer research, encompassing an array of diagnostic and therapeutic approaches for in vivo utilization. These approaches include novel ways of enhancing tumor imaging for earlier detection or delivering toxic therapeutics directly to the site of action, sparing the systemic damage that so often accompanies cancer treatment. However, it is the combination of these essential and orthogonal functionalities that is the hallmark of the promise of nanotechnology. Such materials, coined as "theranostics" for their therapeutic and diagnostic capabilities, allow for a new depth of understanding of the behavior of nanoparticles in vivo, and in particular their efficacy as therapeutic treatments. This dissertation discusses the development of platforms and materials that may be employed as theranostic cancer agents from two distinct philosophical approaches--what may be called "traditional" and "non-traditional" nanotechnology. The "non- traditional" approach details the development of a novel DNA nanoparticle platform created through an exponential enrichment process for selected cell targeting. The products compose a novel class of nanoparticles that possess all of the naturally advantageous properties of DNA. The remainder of the dissertation presents a more "traditional" approach to hierarchical nanoparticle construction, discussing synthesis, stabilization and functionalization of theranostic materials of iron oxide and gold and their combination into novel nanostructures for more efficacious in vivo imaging agents. Ultimately, the preferred path between traditional non-traditional methods rests on whether biological selection is more powerful for functionality than rational design, or whether the most efficacious route is a combination thereof