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Pancreatic cancer remains a major unsolved health problem, with conventional cancer treatments having little impact on disease course. The objective of this thesis is to create innovative tools to better understand and improve chemotherapeutic treatment of pancreatic cancer. Towards this end, nanosystems were designed with a dual purpose: to carry chemotherapeutic drugs and act as photoacoustic imaging contrast agents. The overarching hypothesis is that these nanosystems can provide enhanced therapy for pancreatic cancer and enable visualization of drug delivery. Demonstrated in this dissertation is the design, synthesis, and characterization of two such nanosystems built to carry the chemotherapeutic agent gemcitabine while acting as a photoacoustic imaging contrast agent. The nanosystems were also shown to be multifunctional with possible application as photothermal therapy agents and cellular functional sensors. Although future research is required to fully investigate the clinical potential of these systems for pancreatic cancer, the work presented in this dissertation is a step towards creation of multifunctional nanosystems that will enable non-invasive, in vivo photoacoustic imaging of drug delivery.

Pancreatic cancer remains a major unsolved health problem, with conventional cancer treatments having little impact on disease course. The objective of this thesis is to create innovative tools to better understand and improve chemotherapeutic treatment of pancreatic cancer. Towards this end, nanosystems were designed with a dual purpose: to carry chemotherapeutic drugs and act as photoacoustic imaging contrast agents. The overarching hypothesis is that these nanosystems can provide enhanced therapy for pancreatic cancer and enable visualization of drug delivery. Demonstrated in this dissertation is the design, synthesis, and characterization of two such nanosystems built to carry the chemotherapeutic agent gemcitabine while acting as a photoacoustic imaging contrast agent. The nanosystems were also shown to be multifunctional with possible application as photothermal therapy agents and cellular functional sensors. Although future research is required to fully investigate the clinical potential of these systems for pancreatic cancer, the work presented in this dissertation is a step towards creation of multifunctional nanosystems that will enable non-invasive, in vivo photoacoustic imaging of drug delivery.

This dissertation presents the synthesis and modeling of multicomponent nanosystems templated by self-assembled virus capsids. The design principles, synthesis, analysis, and future directions for these capsid-based materials are presented.Chapter 1 gives an overview of the literature on the application of virus capsids in constructing nanomaterials. The uses of capsids in three main areas are considered: 1) as templates for inorganic materials or nanoparticles; 2) as vehicles for biological applications like medical imaging and treatment; and 3) as scaffolds for catalytic materials. In light of this introduction, an overview of the material in this dissertation is described.Chapters 2-4 all describe integrated nanosystems templated by bacteriophage MS2, a spherical icosahedral virus capsid. MS2 possesses an interior and exterior surface that can be modified orthogonally using bioconjugation chemistry to create multivalent, multicomponent constructs with precise localization of components attached to the capsid proteins.Chapter 2 describes the use of MS2 to synthesize a photocatalytic construct by modifying the internal surface with sensitizing chromophores and the external surface with a photocatalytic porphyrin. The chromophores absorbed energy that the porphyrin could not, and transferred it to the porphyrin via FRET through the protein shell. The porphyrin was then able to utilize the energy to carry out photocatalysis at new wavelengths.In Chapter 3, porphyrins were installed on the interior surface of MS2 and DNA aptamers specific for Jurkat leukemia T cells on the exterior surface. The dual-modified capsids were able to bind to Jurkat cells, and upon illumination the porphyrins generated singlet oxygen to kill them selectively over non-targeted cells.Chapter 4 explores integrating MS2 with DNA origami in order to arrange the capsids at larger length scales. Capsids modified with fluorescent dyes inside and single-stranded DNA outside were able to bind to origami tiles bearing complementary DNA probes. The tiles could then be used to arrange the capsids in a one-dimensional array with dimensions far exceeding those of individual MS2 particles.In Chapter 5, the use of a different capsid, that of the tobacco mosaic virus (TMV) is described. The defect tolerance of light harvesting systems built using TMV as a scaffold was investigated using a kinetic Monte Carlo model to simulate the energy transfer processes. The results of the simulation were used to understand and explain experimental results obtained from the system.