UC San Diego

A variety of materials capable of programmed shape and size changes are found in biological systems, from allosteric enzymes to pseudopodium formation during chemotaxis, and endosomes during cell-uptake processes. By contrast, programmable synthetic supramolecular assemblies of this type are in their infancy, but are expected to have broad utility in a range of applications including targeted delivery and detection. One of the keys to developing these types of materials is understanding how the morphology of the materials affects their properties and interactions with biological systems. This thesis focuses on how to unite two different morphology-dependent properties into a single system. This has allowed access to materials that can be optimized to perform two parallel or competing functions such as longer circulation time in vivo coupled with higher cellular uptake. The first chapter of this thesis describes the importance of developing biohybrid polymeric nanoparticles that use nucleic acids or peptides as biological building blocks incorporated into polymeric nanomaterials. These materials were programmed to undergo well-defined changes in structural features, properties and/or morphology in response to stimuli associated with a given tissue or disease state of interest. Chapter 2 describes the development of DNA-polymeric nanoparticles and their morphologically switchable properties are further applied in programmable pharmacokinetics control in the in vivo system. Chapter 3 describes the development of peptide- hybrid nanoparticles that can undergo morphological switching in response to enzymes. This morphologically switchable peptide-hybrid nanoparticle was applied in targeted accumulation within tumor tissue or myocardial infarcted (MI) tissue. Both of which express inflammatory enzymes to which the particles respond. Chapter 4 describes new methods to characterize or expand the use of the nanoparticle systems described in Chapters 2 and 3, including a new strategy for nanowire fabrication and a new way of determining critical aggregation concentration (CAC) in micelles. Finally, Chapter 5 describes the high- resolution characterization of nanoparticles via an unprecedented super resolution fluorescence imaging technique to characterize the sizes of nanoscale particles in in vivo systems and in ex vivo tissue slices