The utilization of light to produce useful responses holds much potential for changing the world through smart materials and photovoltaic systems. We report the utilization of a variety of carbon nanotube composites as photovoltaic devices or as optothermal materials for the controlled placement of heat. Toward carbon nanotube - polymer photovoltaics we have successfully shown supramolecular compatibilization and functional bilayer devices. Opothermal processes are shown to manipulate a variety of system variables: surface energy, surface tension, and pressure. By manipulating these variables interesting responses are produced. Optothermal surface energy control produced wettability switches of 70º on composite surfaces. Optothermally modulated surface tensions of fluids converted light into work in the form of controlled linear motion, rotational motion, and volumetric expansion. Optothermally heated liquids confined within impermeable microcapsules resulted in the phototriggerable release of chemicals on demand. This release allowed small molecule reactions and polymerizations to be remotely initiated in a spatially selective manner. These results lay the framework for the expansion of the field of advanced optothermally responsive materials.

Polymers are extensively used in the field of drug delivery for many applications. The ability to tailor the physical and in vivo properties of polymers allows them to fulfill many roles in drug delivery. Polymers have found value as both direct drug conjugates and coatings of various other delivery systems such as nanoparticles and liposomes. Here, we investigate both types of systems, polymers as liposome coatings and dendrimers directly bound to siRNA.

Chapter 1 presents a brief overview of polymers and macromolecules in the field of drug delivery. Polymeric drug delivery is a very broad and diverse topic, and this chapter mainly addresses areas within the field that relate directly to this dissertation. The history of polymers in drug delivery is presented, and both current capabilities and challenges are discussed.

Chapter 2 describes the synthesis of two disterol poly(ethylene glycol) (PEG) conjugates for the incorporation into liposomes. PEG has the ability to stabilize lipid membranes, extend circulation half-life in vivo, and protect lipid membranes from other unfavorable interactions that may occur in biological settings. Commonly, PEG conjugated to a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid anchor is used to install PEG onto the surface of lipid monolayers and bilayers. However, PEG-DSPE can phase separate in the membrane surface leading to its possible expulsion from the membrane. Additionally, PEG causes a broadening of the phase transition temperature which makes its use in thermally responsive liposomes challenging. We present the synthesis of two disterol PEG molecules and preliminary characterization of their behavior in lipid membranes.

Chapter 3 is an evaluation of polymers for extended circulation. We investigate the physical and in vivo properties of a panel of polymers for extended circulation on the surface of liposomes as a model platform, although the conclusions drawn are relevant to many types of drug delivery systems. In this chapter we have synthesized well-defined hydrophilic polymers under controlled polymerization techniques and found that all five polymers investigated have lower intrinsic viscosities to that of PEG under consistent experimental conditions. Furthermore, we show that each polymer extends the circulation half-life of liposomes in mice and rats in comparison to conventional liposomes. We also find an immune response and accelerated blood clearance of poly(2‐methyl-2‐oxazoline) (PMOX) coated liposomes upon repeated administration and no such response to the other four polymers in the panel.

Chapter 4 describes the design, synthesis, and in vitro characterization of pH-responsive, biodegradable dendrimers for the delivery of siRNA. Polycationic materials have been extensively investigated for the delivery of RNAi, however, the inherent toxicity of such materials is a major drawback to their use. We envisioned that by installing multiple amines to a dendrimer core through pH-sensitive hydrazone linkages we would be able to circumvent this roadblock to RNAi delivery. Furthermore, by designing a biodegradable dendrimer with orthogonal sets of functional groups, we were able to install other delivery aids onto the dendrimer periphery. In an in vitro firefly luciferase knockdown assay, polymers displayed decreased toxicity in comparison to other cationic delivery strategies and modest knockdown capabilities.

Chapter 5 gives a brief overview of the findings presented in this dissertation followed by a short perspective on the future of polymers in the field of drug delivery.

The major body of this work investigates how the chemical structure of conjugated polymers relates to the fundamental operating mechanism of organic photovoltaic devices. New conjugated polymers were characterized and their optical and electronic properties tested and correlated with their power conversion efficiencies as the active layer in polymer solar cells. From these experiments general structure/function relationships are drawn with an eye toward developing universal guidelines for conjugated polymer design and synthesis.

Starting with light absorption, three major steps in the photovoltaic mechanism are examined. First, photogeneration of excited states and the migration of these states through the active layer are correlated to the polymeric backbone chemistry and the resulting device performance. Next, separation of these excited states at an interface between electron donors and electron acceptors is examined as a function of donor-acceptor distance and active layer dielectric constant. These two variables were tuned by chemical modification of polythiophene side groups. Third, charge carrier conduction is related to both polymer electronic states and to solid-state packing morphology. Design principles for effective conduction of both holes and electrons are outlined and the ambipolar nature of conjugated organic materials is discussed.

In the final chapters, the solid-state polymer morphology in a solution processed thin film is examined. The impact that this morphology has on all steps in the photovoltaic mechanism is highlighted. How chemical modification of the polymer can influence this packing structure is examined as well as how new fabrication procedures can be used to pre-form nanostructured materials in solution before thin film deposition.

Drug delivery is generally concerned with improving the pharmacokinetics of therapeutic molecules. This can be done by improving distribution to target tissues, improving biological retention time, co-delivery of multiple therapeutics, and decrease in the total amount of therapeutic necessary to get the desired effect. Because they are highly tunable and synthetically addressable, polymeric particulate carriers represent a promising approach for improved delivery of therapeutics, and are the subject of this dissertation. In particular, the development is described for degradable materials, which are capable of releasing encapsulated cargo following uptake by cells and subsequent trafficking to endosomal vesicles. Degradation is responsive to acidic or oxidizing environments found in targeted tissues. Materials developed include hydrogels, hydrophobic microparticles, and liquid-filled microcapsules.

Chapter 1 introduces various delivery strategies for polymeric delivery vehicles and some of their main applications. Additionally, the modes of environmentally responsive degradation are reviewed, with a focus on relevant design criteria for materials intended for delivery applications.

In Chapter 2, the synthesis of a multifunctional acid-sensitive hydrogel carrier is described for immunotherapy applications. Antigen and an immunostimulatory adjuvant are encapsulated in particles decorated with targeting antibodies and the effectiveness of stimulation and targeting are assayed.

Chapters 3 and 4 discuss the synthesis and characterization of a hydrophobic acid-sensitive delivery vehicle based on acetal-modified dextran. The preparation of particles from acetal- modified dextran and their pH-dependent degradation behavior is described. Further

optimization acetal modification and its effect on degradation rate and uptake pathways are investigated.

Chapter 5 describes the synthesis and characterization of a hydrophobic oxidation-sensitive delivery vehicle based on a modified dextran. The preparation of particles, their degradation profile, and their use in a proof-of-principle immunostimulation experiment is described.

Chapter 6 describes the synthesis and characterization of a acid-sensitive liquid-filled microcapsules with burst release kinetics. The preparation and degradation of these capsules is investigated and their use in a proof-of-principle cytotoxicity experiment is described.

Chapter 7 describes preliminary work toward the development of materials that feature autocatalytic acid-mediated degradation.

The efficacy of chemotherapy drugs is often hampered by poor molecule properties, such as solubility, rapid excretion, indiscriminate toxicity, and lack of targeting to tumor tissue. Macromolecular carriers have been explored for their potential to modulate drug pharmacokinetics and increase tumor uptake through passive targeting. In this work, I examined the design of delivery systems to optimize the delivery of chemotherapeutics. An introduction to polymer and liposomal drug delivery vehicles is presented in Chapter 1. The benefits and challenges with each delivery scaffold, as opposed to conventional chemotherapies, are discussed. The remainder of the chapter will focus on camptothecin and platinum (II) drug delivery in the context of combination therapies and controlled release.

In Chapter 2, the design of camptothecin pro-drugs for pH sensitive release through a hydrazone bond is explored. I describe the synthesis of a poly-lysine dendrimer, to which camptothecin is conjugated. The synthesis of a new, more synthetically accessible PEGylated ester amide dendrimer is presented. The dendrimer was appended with both camptothecin and doxorubicin to investigate drug synergy for a dual-drug delivery system.

In Chapters 3 and 4, polymer Pt (II) drug delivery is explored in collaboration with Dr. Derek van der Poll. A PEGylated ester amide dendrimer is modified with a variety of amino acid inspired chelators to study how platinum release is correlated with cytotoxicity and efficacy. Both a fast and slow releasing chelator were evaluated in vivo. Next, a series of ketone containing bidentate Pt (II) drugs were synthesized. Increasingly cytotoxic complexes could be designed by cross coupling additional aromatic ligands, exploring electronic considerations, and modifying platinum ring sizes. Although Pt content was substantially increased in tumors, this did not translate to increased efficacy in the C26 murine colon carcinoma tumor model.

Chapter 5, in collaboration with Aditya Kohli and Darren Chan, presents an introduction to the utility of sterol modified lipids (SML). The bilayer properties of liposomes composed of SMLs were characterized using fluorescence anisotropy measurements and content release assays. The influence of the acyl chain length in the SML on contents release is discussed. A pharmacokinetic study indicated that changes in the SML used to form the liposome controlled the release of the liposome contents but did not influence the circulation time of the liposome. This finding highlights one of the advantages of the SMLs for creating a circulating reservoir of drug which could be advantages for tumor targeting.

In Chapter 6, liposomes composed of SMLs or traditional lipids are prepared to control the release of cisplatin over a range of release rates. I investigated a variety of procedures for encapsulating cisplatin in the liposome and selected the ethanol loading procedure as the best one to obtain good Pt encapsulation with retention of activity. These were used to test the hypothesis that liposomal cisplatin formulations with an intermediate release rate would have improved anti-tumor properties compared to liposomes with slow release rates; however non-leaky formulations had a better anti-tumor efficacy. In an attempt to understand why this was the case, I measured both the distribution of platinum in the tumor using X-ray fluorescence spectroscopy as well as the formation of Pt-DNA adducts in the tumor for free and liposomal cisplatin. All formulations had substantially more Pt in the tumors and a greater amount of Pt-DNA adducts formed than the free cisplatin. Thus, the reason for why liposomal cisplatin formulations do not provide a substantially better anti-tumor effect than the free compound remains elusive.

This work describes the synthesis, and study of new organic and organometallic compounds designed to possess modified excited states for applications in electronic devices, with a particular focus on photovoltaics. The first chapter introduces the origin of semiconducting behavior in conjugated polymers, and how the properties of these semiconductors ultimately impact the fundamental physical processes occurring in organic electronic devices. The second chapter describes the synthesis, optoelectronic properties, and photovoltaic performance of a small molecule oligothiophene analog that possesses a considerable redshift in absorption relative to an unmodified oligothiophene. This redshift in absorption is the result of using a fused thiophene unit that acts as a driving force to enable dearomatization of the oligothiophene unit. The third chapter describes the preparation of wide band gap, phosphorescent cyclometalated platinum polymers and their application to bilayer photovoltaic devices where an increase in photocurrent is observed, and is attributed to an increase in the exciton diffusion length arising from formation of triplet excitons. The fourth chapter presents further development of cyclometalated platinum polymers, with a focus on tuning the photophysical properties and studying these materials in bulk heterojunction photovoltaic devices. The fifth chapter presents a study of cyclometalated platinum and iridium small molecules, describing their photophysical properties and solid-state structure, and exploring the application of these complexes to light emitting diodes. The final chapter describes the development of polythiophenes containing highly polarizable functional groups, with particular attention to the effect of these modifications on the optoelectronic properties and the dielectric constants of the resulting polymers. Together, these chapters present a study encompassing the modification of excited states in organic semiconductors, beginning with light absorption, continuing to modification of the spin state of the exciton, and ultimately modifying the dielectric constant of the active layer materials to affect charge separation and transport. Utilizing materials developed based on these principles provides an attractive new route to altering and enhancing the basic steps involved in the operation of organic electronic devices, ultimately producing both an improved understanding of the mechanism of device operation, and improved device performance.

The concept of self-assembled dendrimers is explored for the creation of discrete nanoparticle assemblies. Hybridization of branched DNA trimers and nanoparticle-DNA conjugates results in the synthesis of nanoparticle trimer and tetramer complexes. Multiple tetramer architectures are investigated, utilizing Au-DNA conjugates with varying secondary structural motifs. Hybridization products are analyzed by gel electrophoresis, and discrete bands are observed corresponding to structures with increasing numbers of hybridization events. Samples extracted from each band are analyzed by transmission electron microscopy, and statistics compiled from micrographs are used to compare assembly characteristics for each architecture. Asymmetric structures are also produced in which both 5 and 10 nm Au particles are assembled on branched scaffolds.