Polymer materials have become important tools in nanomanufacturing due to their facile processing and ready attainment of the necessary feature sizes. The development of cleavable junctions has led to advances in the production of polymer nanotemplates. Photocleavage strategies have come to the forefront of the field because photons, as a cleavage stimulus, do not have the mass-transport limitations of chemical methods, and provide for targeted two- and three-dimensional feature control. This dissertation presents a method for producing photocleavable materials by one-pot copper-catalyzed azide-alkyne "click" chemistry (CuAAC), activator regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and activated ester substitution methods that have each block labeled with a fluorescent dye, enabling exploration of the polymer physics of these systems by correlation fluorescence spectroscopy. It also introduces a novel photocleavable linker, the o-nitrobenzyl-1,2,3-triazole, its behavior on photocleavage, and a facile method for the production of the o-nitrobenzyl azides necessary for their synthesis. The synthesis and properties of a bulk photodegradable polytriazole are reported, as are proof of concept experiments demonstrating its potential as a directly photoetchable material. Lastly, this dissertation contains a perspective on possible avenues of new research on the topics presented.

This dissertation explores the use of block copolymers which can self-assemble into different morphologies as templates to fabricate nanostructured materials. The first section (Chapters 2-4) reports the formation of mesoporous silica films with spherical, cylindrical and bicontinuous pores up to 40 nm in diameter through replicating the morphologies of the solid block copolymer (BCP) templates, polystyrene-b-poly(tert-butyl acrylate) (PS-b-PtBA), via phase selective condensation of tetraethylorthosilicate in supercritical CO2. Next, directed self-assembly was used to control the orientation of cylindrical domains in PS- b-PtBA templates. Large-area aligned mesochannels in silica films with diameters tunable between 5 and 30 nm were achieved through the replication of oriented templates via scCO2 infusion. The long-range alignment of mesochannels was confirmed through GISAXS with sample stage azimuthal rotation. In the second section (Chapters 5-6), enantiopure tartaric acid was used as an additive to dramatically improve ordering in poly(ethylene oxide-block- tert-butyl acrylate) (PEO-b-PtBA) copolymers. Transmission electron microscopy (TEM), atomic force microscopy (AFM) and X-ray scattering were used to study the phase behavior and morphologies within both bulk and thin films. With the addition of a photo acid generator, photo-induced disorder in the PEO-b-PtBA/tartaric acid composite system was achieved upon UV exposure which deprotected the PtBA block to yield poly(acrylic acid) (PAA), which is phase-miscible with PEO. Area-selective UV exposure using a photo-mask was applied with the assistance of trace amounts of base quencher to achieve high-resolution hierarchical patterns. Helical superstructures were observed by TEM in this BCP/chiral additive system with 3D handedness confirmed by TEM tomography. In the last section (Chapter 7), ultra-high loadings of nanoparticles into target domains of block copolymer composites were achieved by blending the block copolymer hosts with small molecule additives that exhibit strong interactions with one of the polymer chain segments and with the nanoparticle ligands via hydrogen bonding. The addition of 40 wt% D-tartaric acid to poly(ethylene oxide-block-tert-butyl acrylate) (PEO-b-PtBA) enabled the loading of up to 150 wt% of 4-hydroxythiophenol functionalized Au nanoparticles relative to the mass of the target hydrophilic domain. This was equivalent to over 40% Au by mass of the resulting well ordered composite as measured by thermal gravimetric analysis.

Increasing motivation for the development of nanotechnology with applications in sensing, nanotheranostics, combinatorial therapy and drug/protein delivery have brought a broad spectrum of multifunctional polymeric materials. With interest in obtaining more efficient methods for fast and accurate diagnostics, nanostructures able to rapidly obtain large sets of data for analyte sensing are necessary. Likewise, interests in, not only obtaining accurate diagnostics, but also being able to concurrently and accurately provide therapy has inspired us to develop such technologies. We particularly focus on understanding the assembly and disassembly processes of polymeric nanostructures in response to biologically relevant stimuli. We are interested in mimicking natural sensing events and take advantage of the differential binding affinity of a set of receptors to generate analyte-specific patterns to use as sensors. Receptors developed in our laboratories have demonstrated impressive recognition capabilities for proteins. When a set of polyelectrolytes and surfactants with different hydrophobic and electronic properties, as well as the guest molecule (transducer) with different characteristics, are combined, fluorescence patterns for proteins can be generated. Creating patterns using protein-induced disassembly not only provides the opportunity to have a new method for sensing analytes that are not electronically complementary to the fluorescent transducers, but also reduces the synthetic complexity even further, since these are assembled from its components noncovalently. A versatile and efficient delivery vehicle should have a tunable particle size, provide protection and stability to the cargo to prevent premature release before approaching the target site and should provide ease of cargo incorporation strategies. This ease of incorporation becomes more challenging when we are talking about incorporating molecules with different characteristics. Here we demostrate the versatility of self-crosslinked polymeric nanogels on the incorporation of lipophilic small molecules on its interior and hydrophilic proteins at the surface. Also, different approaches of protein incorporation can be obtained using these polymeric nanogels, which provide differences in protein release and cell internalization. These technologies were found to be potential candidates for applications such as nanotheranostics, combinatorial therapy and protein delivery.

The design and engineering of nanoscopic drug delivery vehicles that stably encapsulate lipophilic drug molecules, transport their loaded cargo to specific target sites, and release their payload in a controlled manner are of great interest in therapeutic applications, especially for cancer chemotherapy. This dissertation focuses on chemically cross-linked, water-soluble polymer nanoparticles, termed nanogels, which constitute a promising scaffold and offer the potential to circumvent encapsulation stability issues. A facile synthetic method for a new class of self-cross-linked polymer nanogels, synthesized by an intra/intermolecular disulfide cross-linking reaction in aqueous media, is described here. This simple emulsion-free method affords noncovalent lipophilic guest encapsulation and surface functionalization that may allow for targeted delivery. The encapsulation stability of lipophilic molecules sequestered within these nanoscopic containers is evaluated by a fluorescent resonance energy transfer (FRET) based method developed by our research group. We demonstrate that the encapsulation stability of noncovalently encapsulated guest molecules in disulfide cross-linked polymer nanogels can be tuned and that guest release can be achieved in response to a biologically relevant stimulus (GSH). In addition, varied hydrophobicity in the self-cross-linked nanogels affects the lipophilic loading capacity and encapsulation stability. We reveal that optimal loading capacity is limited by encapsulation stability, where over-loading of lipophilic molecules in the nanoscopic containers may cause undesirable leakage and severely compromise the viability of such systems for drug delivery and other biological applications.