The emerging field of RNA nanotechnology necessitates creation of functional RNA nanoparticles, but has been limited by particle instability. Previously, it was found the three-way junction (3WJ) of the Phi29 DNA packaging motor pRNA was found to be ultra-stable and assemble in solution without the presence of metal ions. The three-way junction is composed of three short oligo RNA strands and proven to be thermodynamically stable. Here the assembly mechanism, thermodynamic and enzymatic stabilities, and kinetics are examined in order to understand the stability behind this unique motif. Thermodynamic and kinetics studies found that the pRNA 3WJ formed out of three components at a rapid rate creating a single-step three component collision with a lack of dimer intermediate formation while being governed by entropy, instead of the commonly seen enthalpy. Furthermore, the pRNA 3WJ proved to be stable at temperatures above 50 °C, concentrations below 100 pM, and produced a free energy of formation well below other studied RNA structures and motifs. With the high stability and folding efficiency of the pRNA 3WJ, it serves as an ideal platform for multi-branched RNA nanoparticles constructed through bottom-up techniques. RNA nanoparticles were constructed for the specific targeting of prostate cancer cells expressing Prostate Specific Membrane Antigen (PSMA) by receptor mediated endocytosis through the addition of an RNA aptamer; and the delivery of anti-miRNA sequences for gene regulation. The resulting nanoparticles remained stable while showing highly specific binding and entry in PSMA positive cells through cell surface receptor endocytosis. Furthermore, the entry of the nanoparticles allowed for the knockdown of against onco-miRNAs. Nanoparticles harboring antimiRNAs led to the upregulation of tumor suppressor genes, and signaling of apoptotic pathways. These findings display RNA nanotechnology can result in the production of stable nanoparticles and result in the specific treatment of cancers, specifically prostate cancer.

A novel electrochemical method to generate nm-scale bubbles at the tips of CNTs can temporarily block the membrane. A 92% blocking efficiency is achieved when the bubbles are stabilized in 30-60 nm diameter „wells‟ at the tips of CNTs. This well is formed by the electrochemical oxidation of the conductive CNTs partially into the polymer matrix of the membrane. Meanwhile, the nanoscale bubbles can be removed with 0.004 atm pressure to recover the transport through the CNT membrane. The CNT membrane with nanoscale bubble valve system was used to demonstrate electrochemical energy storage. Uniform ultrathin Pt films were electrodeposited onto an aligned array of carbon nanotubes (CNTs) for high-area chemically stable methanol fuel cell anodes. Electrochemical treatment of the graphitic CNT surfaces by diazonium benzoic acid allowed for uniform Pt electroplating. The mass activity of the Pt thin film can reach 400 A/g at a scan rate of 20 mV/s and in a solution of 1 M CH3OH/0.5 M H2SO4. A novel programmed pulse potential at 0 V was also seen to nearly eliminate the effects of carbon monoxide poisoning on catalyst Pt. Furthermore, the Pt monolayer was deposited on buckypaper by replacing the precursor Cu monolayer coated on CNTs by the underpotential deposition. The electrochemical surface modification of graphite CNTs by fluorinated benzoic acid was critical to coordinate Cu ions for monolayer formation. The mass activity of the monolayer can be improved to the record value of 2711 A/g. This is about 13 times higher than that of the ~10 nm thick Pt film coated on MWCNTs. Besides the high mass activity, the Pt monolayer coated on buckypaper can be used as catalyst for fuel cells with several advantages such as low cost, high surface area, flexibility, mechanical robustness and enhanced pressure flow. Finally, a new strategy has been developed toward electrochemical water oxidation with Ir complexes catalyst, which was grafted on buckypaper by direct binding to enhance catalyst activity. The TOF (turn over frequency) of the Ir catalyst for water splitting was 7.9 s-1 at the constant potential of 1.4 V vs Ag/AgCl.

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives and for therapeutic intervention as a putative antioxidant. However, the biological effects of ceria ENM exposure have yet to be fully defined. Both pro-and anti-oxidative effects of ceria ENM exposure are repeatedly reported in literature. EPA, NIEHS and OECD organizations have nominated ceria for its toxicological evaluation. All these together gave us the impetus to examine the oxidative stress effects of ceria ENM after systemic administration. Induction of oxidative stress is one of the primary mechanisms of ENM toxicity. Oxidative stress plays an important role in maintaining the redox homeostasis in the biological system. Increased oxidative stress, due to depletion of antioxidant enzymes or molecules and / or due to increased production of reactive oxygen (ROS) or nitrogen (RNS) species may lead to protein oxidation, lipid peroxidation and/or DNA damage. Increased protein oxidation or lipid peroxidation together with antioxidant protein levels and activity can serve as markers of oxidative stress. To investigate the oxidative stress effects and the mechanisms of ceria-ENM toxicity, fully characterized ceria ENM of different sizes (~ 5nm, 15nm, 30nm, 55nm and nanorods) were systematically injected into rats intravenously in separate experiments. Three brain regions (hippocampus, cortex and cerebellum) were harvested from control and ceria treated rats after various exposure periods for oxidative stress assessment. The levels of oxidative stress markers viz. protein carbonyl (PC), 3-nitrotyrosine (3NT), and protein bound 4-hydroxy-2-trans-nonenal (HNE) were evaluated for each treatment in each control and treated rat organ. Further, the levels and activities of antioxidant proteins, such as catalase, glutathione peroxidase (GPx), glutathione reductase (GR), super oxide dismutase (SOD), were measured together with levels of heat shock proteins heme oxygenase -1 and 70 (HO-1 and Hsp-70). In addition, the levels of pro-inflammatory cytokines IL-1β, TNF-α, pro-caspase-3, and autophagy marker LC-3A/B were measured by Western blot technique. In agreement with the literature-proposed model of oxidative stress hierarchy mechanism of ENM-toxicity, the statistical analysis of all the results revealed that the ceria ENM-induced oxidative stress mediated biological response strongly depends on the exposure period and to some extent on the size of ceria ENM. More specifically, a single intravenous injection of ceria ENM induced tier-1 (phase-II antioxidant) response after shorter exposure periods (1 h and 20 h) in rat brain. Upon failure of tier-1 response after longer exposure periods (1 d to 30 d), escalated oxidative stress consequently induced tier-2 and tier-3 oxidative stress responses. Based on our observations made at chronic exposure period (90 d) after the single i.v. injection of ceria ENM, we could extend the model of oxidative stress hierarchy mechanisms for ceria-ENM-induced toxicity. Considering the evaluation of all the oxidative stress indices measured in 3-brain regions, oxidative stress effects were more prominent in hippocampus and the least in cerebellum, but no specific pattern or any significant difference was deduced.

Neuropeptidases are responsible for degradation of signaling peptides in the central nervous system and periphery. Some neuropeptidases have also been shown to play a role as part of the cell’s hydrolytic machinery responsible for breaking down proteins and peptides into amino acids, and these enzymes therefore influence small peptide availability for antigen presentation. A better understanding of how neuropeptidases recognize their substrates could lead to therapeutics that modulate the activity of these important enzymes. Alternatively, re-engineering these enzymes to selectively hydrolyze undesirable peptides could make them attractive as therapeutics themselves. A key question in understanding the activity of these enzymes is how they are able to recognize a variety of seemingly unrelated amino acid sequences as cleavage sites. We are investigating the basis for this general substrate recognition in neuropeptidases using thimet oligopeptidase (TOP) as a model. Crystal structures of TOP in complex with a variety of substrates and inhibitors shed light on the mechanisms underlying substrate recognition and pave the way for re-targeting substrate recognition in these enzymes. Nano test tube particles have been proposed as a means of delivering therapeutics such as enzymes. However, the template synthesis method for nano test tube production does not produce therapeutic quantities. In order to take full advantage of re-engineered neuropeptidases a new method for nano test tube synthesis has been developed. We show that a non-destructive template synthesis methodology can be applied to produce nano test tube particles in quantities useful for therapeutic enzyme immobilization.

The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate both pure and hybrid nanocrystals, evaluate their performance in vitro and in vivo, and investigate the extent of tissue distribution and tumor accumulation in a murine model. Pure and hybrid nanocrystals of several model drugs, including paclitaxel (PTX), camptothecin, and ZSTK474, were precipitated by the antisolvent method in the absence of stabilizer, and their size was further minimized by homogenization. The nanocrystals of PTX, which is the focus of the study, had particle size of approximately 200 nm and close-to-neutral surface charge. Depending on the cell type, PTX nanocrystals exerted different level of cytotoxicity. In human colon and breast cancer xenograft models, nanocrystals yielded similar efficacy as the conventional formulation, Taxol, at a dose of 20 mg/kg, yet induced a reduced toxicity. Biodistribution study revealed that 3H-PTX nanocrystals were sequestered rapidly by the macrophages upon intravenous injection. Yet, apparent toxicity was not observed even after four weekly injections. The sequestered nanocrystals were postulated to be released slowly into the blood circulation and reached the tumor. Tritium-labeled-taxol, in contrast, was distributed extensively to all the major organs, inducing systemic toxicity as observed in significant body weight loss. The biodistribution results obtained from radioactive analysis and whole-body optical imaging was compared. To some degree, the correlation was present, but divergence in the quantitative result, due to nanocrystal integrity and limitations associated with the optical modality, existed. Despite their promising properties, nanocrystal suspensions must be securely stabilized by stealth polymers in order to minimize opsonization, extend blood-circulation time, and efficiently target the tumor.

Continued dimensional scaling of CMOS processes is approaching fundamental limits and therefore, alternate new devices and microarchitectures are explored to address the growing need of area scaling and performance gain. New nanotechnologies, such as memristors, emerge. Memristors can be used to perform stateful logic with nanowire crossbars, which allows for implementation of very large binary networks that can be easily reconfigured. This research involves the design of a memristor-based massively parallel datapath for various applications, specifically SIMD (Single Instruction Multiple Data) like architecture, and parallel pipelines. The dissertation develops a new model of massively parallel memristor-CMOS hybrid datapath architectures at a systems level, as well as a complete methodology to design them. One innovation of the proposed approach is that the datapath design is based on space-time diagrams that use stateful IMPLY gates built from binary memristors. This notation aids in the circuit minimization in logic design, calculations of delay and memristor costs, and sneak-path avoidance. Another innovation of the proposed methodology is a general, new, architecture model, MsFSMD (Memristive stateful Finite State Machine with Datapath) that has two interacting sub-systems: 1) a controller composed of a memristive RAM, MsRAM, to act as a pulse generator, along with a finite state machine realized in CMOS, a CMOS counter, CMOS multiplexers and CMOS decoders, 2) massively parallel, pipelined, datapath realized with a new variant of a CMOL-like nanowire crossbar array, MsCMOL (Memristive stateful CMOL), with binary stateful memristor-based IMPLY gates. Next contribution of the dissertation is the new type of FPGA. In contrast to the previous memristor-based FPGA (mrFPGA), the proposed MsFPGA (Memristive stateful logic Field Programmable Gate Array) uses memristors for memory, connections programming, and combinational logic implementation. With a regular structure of square abutting blocks of memristive nanowire crossbars and their short connections, proposed architecture is highly reconfigurable. As an example of using the proposed new FPGA to realize biologically inspired systems, the detailed design of a pipelined Euclidean Distance processor was presented and its various applications are mentioned. Euclidean Distance calculation is widely used by many neural network and associative memory based algorithms.

This work presents a new low-temperature fabrication process of metal oxide nanostructures that allows high-aspect ratio zinc oxide (ZnO) and titanium dioxide (TiO2) nanowires and nanotubes to be readily integrated with microelectronic devices for sensor applications. This process relies on a new method of forming a close-packed array of self-assembled high-aspect-ratio nanopores in an anodized aluminum oxide (AAO) template in a thin (2.5 µm) aluminum film deposited on a silicon and lithium niobate substrate (LiNbO3). This technique is in sharp contrast to traditional free-standing thick film methods and the use of an integrated thin aluminum film greatly enhances the utility of such methods. We have demonstrated the method by integrating ZnO nanowires, TiO2 nanowires, and multiwall TiO2 nanotubes onto the metal gate of a MOSFET (Metal-Oxide-Semiconductor Field-Effect Transistor), and the delay line of a surface acoustic wave (SAW) device to form an integrated ChemFET (Chemical Field-Effect Transistor) and a orthogonal frequency coded (OFC) SAW gas sensor. The resulting metal oxide nanostructures of 1-1.7 µm in height and 40-100 nm in diameter offer an increase of up to 220X the surface area over a standard flat metal oxide film for sensing applications. The metal oxide nanostructures were characterized by SEM, EDX, TEM and Hall measurements to verify stoichiometry, crystal structure and electrical properties. Additionally, the electrical response of ChemFETs and OFC SAW gas sensors with ZnO nanowires, TiO2 nanowires, and multiwall TiO2 nanotubes were measured using 5-200 ppm ammonia as a target gas at room temperature (24ºC) showing high sensitivity and reproducible testing results.

Silicon-based electrodes are the most promising negative electrodes for the next generation high capacity lithium ion batteries (LIB) as silicon provides a theoretical capacity of 3579 mAh g-1, more than 10 times higher than that of the state-of-the-art graphite negative electrodes. However, silicon-based electrodes suffer from poor cycle life due to large volume expansion and contraction during lithiation/delithiation. In order to improve the electrochemical performance a number of strategies have been employed, such as dispersion of silicon in active/inactive matrixes, devising of novel nanostructures, and various coatings for protection. Amongst these strategies, silicon-carbon coating based composites are one of the most promising because carbon coating is comparatively flexible, easy to obtain, and scalable with various industrial processes. Low cost and renewable lignin, which constitutes up to 30% dry mass of the organic carbon on earth, is widely available from paper and pulp mills which produce lignin in excess of 50 million tons annually worldwide. It is a natural bio-polymer with high carbon content and highly interconnected aromatic network existing as a structural adhesive found in plants. Generally burnt for energy on site, lignin is gradually finding its way into high value-added products such as precursor for carbon fibers, active material in negative electrodes, and raw material for supercapacitors. This dissertation focuses on high performance silicon-based negative electrodes utilizing lignin as the carbon precursor for conductive additive, binder, and carbon coating. To my knowledge this is one of the first works attempting to utilize and summarize the performance of lignin in silicon-based negative electrodes. The first part of the dissertation shows that silicon-lignin composites treated at 800 ºC displayed good capacity and cycling performance. The second part goes to generalize the effect of temperature on silicon-lignin composites and shows that a low temperature treatment granted an electrode with superior performance and cycling properties owing to the preservation of polymeric properties of lignin. The final part of the dissertation discusses the current research trends in SiOx based negative electrodes and extends lignin to that field. This dissertation will, hopefully, provide knowledge and insight for fellow researchers wishing to utilize lignin or other renewable resources in devising advanced battery electrodes.

The key challenge for a nanomaterial based sensor is how to synthesize in bulk quantity and fabricate an actual device with insightful understanding of operational mechanisms during performance. I report here effective, controllable methods that exploit the concepts of the "green approach" to synthesize two different one-dimensional nanostructures, including tin oxide nanowires and carbon nanotubes. The syntheses are followed by product characterization and sensing device fabrications as well as sensor performance understanding at the molecular level. Sensor-analyte response and recovery kinetics are also presented. The first part of the thesis describes bulk-scale synthesis and characterization of tin oxide nanowires by the molten salt synthetic method and the nanowire doping with antimony (n-types) and lithium. The work builds on the success of using n-doped SnO2 nanoparticles to selectively detect chlorine gas at room temperature. Replacing n-doped nanoparticles with n-doped nanowires reduces the number of inter-particle electron hops between sensing electrodes. The nanowire based sensors show unprecedented 5 ppb detectability of corrosive Cl2 gas concentration in air. At the higher range, 10 ppm of Cl2 gas leads to a 250 fold increase in the device resistance. During sensor recovery, FT-IR studies show that dichlorine monoxide (Cl2O) and chlorine dioxide (ClO2) are the desorbing species. Long term stability of devices is affected by lattice oxygen vacancies replaced by chlorine atoms. Bulk-scale synthesis of multiwall carbon nanotube (MWCNTs) was achieved by a novel inexpensive synthetic method. The green chemistry method uses the non-toxic and easy to handle solid carbon source naphthalene. The synthesis is carried out by simply heating naphthalene and organometallic precursors as catalysts in a sealed glass tube. Synthesis at 610º C leads to MWCNTs of 50 nm diameter and lengths exceeding well over microns. MWCNT doping is attempted with nitrogen (n-type) and boron (p-type) precursors. Palladium nanoparticles decorated on as-synthesized MWCNTs are employed for specific detection of explosive hydrogen gas with concentrations far below the explosive concentration limits. During performance, the sensor exhibits abnormal response behaviors at hydrogen gas concentrations higher than 1%. A model of charge carrier inversion, brought about by reduction of MWCNT by hydrogen molecules dissociated by Pd nanoparticles is proposed.

Various synthetic methods have been developed to produce metal nanostructures including copper and iron nanostructures. Modification of nanoparticle surface to enhance their characteristic properties through surface functionalization with organic ligands ranging from small molecules to polymeric materials including organic semiconducting polymers is a key interest in nanoscience. However, most of the synthetic methods developed in the past depend widely on non-aqueous solvents, toxic reducing agents, and high temperature and high-pressure conditions. Therefore, to produce metal nanostructures and their nanocomposites with a simpler and greener method is indeed necessary and desirable for their nano-scale applications. Hence the objective of this thesis work is to develop an environmentally friendly synthesis method to make welldefined copper and iron nanostructures on a large-scale. The size and shape-dependent optical properties, solid-state crystal packing, and morphologies of nanostructures have been evaluated with respect to various experimental parameters. Nanostructures of copper and iron were prepared by developing an aqueous phase chemical reduction method from copper(II) chloride and Fe(III) chloride hexahydrate upon reduction using a mild reducing agent, sodium borohydride, under an inert atmosphere at room temperature. Well-defined copper nanocubes with an average edge length of 100±35 nm and iron nanochains with an average chain length up to 1.70 μm were prepared. The effect of the molar ratios of each precursor to the reducing agent, reaction time, and addition rate of the reducing agent were also evaluated in order to develop an optimized synthesis method for synthesis of these nanostructures. UV-visible spectral traces and X-ray powder diffraction traces were obtained to confirm the successful preparation of both nanostructrues. The synthesis method developed here was further modified to make poly(3-hexylthiophene) coated iron nanocomposites by surface functionalization with poly(3-hexylthiophene) carboxylate anion. Since these nanostructrues and nanocomposites have the ability to disperse in both aqueous-based solvents and organic solvents, the synthesis method provides opportunities to apply these metal nanostructures on a variety of surfaces using solution based fabrication techniques such as spin coating and spray coating methods.