Hydrophobic drug paclitaxel nanoparticles (PAX NPs) and pH sensitive hydrogels were prepared in this study to build a colon targeting nanoparticle based drug delivery system for oral administration. Negative charged PAX NPs at the size of 110 +/- 10 nm were fabricated, characterized and then encapsulated in synthetic / biomacromolecule shell chitosan, dextran-sulfate using a layer by layer (LbL) self-assembly technique. Surface modifications were performed by covalently conjugating with poly (ethylene glycol) (H2N-PEG-carboxymethyl, Mw 3400) and fluorescence labeled wheat germ agglutinin (F-WGA), so as to build a biocompatible and targeted drug delivery system. Extended release of drug paclitaxel can be realized by adding more polyelectrolyte layers in the shell. High cell viability with PEG conjugated and high binding capacities of WGA modified nanoparticles with Caco-2 cells were observed. Preliminary study on stability of the nanoparticles in suspension at different pH was also performed. Two dextran based pH sensitive and enzyme degradable hydrogels: dextran maleic acid (Dex-MA), and glycidyl methacrylated dextran (Dex-GMA) were synthesized for oral delivery of nanoparticles. Hydrogels of both kinds were stable in simulated gastric fluid, but were prone to swelling and degradation in the presence or absence of enzyme dextranase in simulated intestinal fluid. The release profiles of nanoparticles could be tuned from 5 hr to 24 hr periods of time with more than 85% of the nanoparticle released in the simulated intestinal fluid. The release of PAX NPs was completed with longer time periods (45 hr-120 hr). Two possible release mechanisms were discussed for Dex-MA and Dex-GMA-co-AA hydrogels respectively: degradation controlled, and diffusion controlled. These biodegradable hydrogels, which can release nanoparticles depending on pH changes, together with the biocompatible and targeted nanoparticles, may be suitable as a potential colon targeting system for oral delivery of drug nanoparticles.

A main driving force behind the recent years’ immense interest in nanoscience and nanotechnology is the possibility of achieving new material properties and functionalities within, e.g., material physics, biomedicine, sensor technology, chemical catalysis, energy storing systems, and so on. New (theoretical) possibilities represent, in turn, a challenging task for chemists and physicists. An important feature of the present nanoscience surge is its strongly interdisciplinary character, which is reflected in the present work. In this thesis, nanocrystals and thin films of magnetic and ferroelectric metal oxides, e.g. RE2O3 (RE = Y, Gd, Dy), GdFeO3, Gd3Fe5O12, Na0.5K0.5NbO3, have been prepared by colloidal and sol-gel methods. The sizes of the nanocrystals were in the range 3-15 nm and different carboxylic acids, e.g. oleic or citric acid, were chemisorbed onto the surface of the nanoparticles. From FT-IR measurements it is concluded that the bonding to the surface takes place via the carboxylate group in a bidentate or bridging fashion, with some preference for the latter coordination mode. The magnetic properties of nanocrystalline Gd2O3 and GdFeO3 were measured, both with respect to magnetic resonance relaxivity and magnetic susceptibility. Both types of materials exhibit promising relaxivity properties, and may have the potential for use as positive contrast enhancing agents in magnetic resonance imaging (MRI). The nanocrystalline samples were also characterised by transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS), and quantum chemical calculations. Thin films of Na0.5K0.5NbO3, GdFeO3 and Gd3Fe5O12 were prepared by sol-gel methods and characterized by x-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). Under appropriate synthesis conditions, rather pure phase materials could be obtained with grain sizes ranging from 50 to 300 nm. Magnetic measurements in the temperature range 2-350 K indicated that the magnetization of the perovskite phase GdFeO3 can be described as the sum of two contributing terms. One term (mainly) due to the spontaneous magnetic ordering of the iron containing sublattice, and the other a susceptibility term, attributable to the paramagnetic gadolinium sublattice. The two terms yield the relationship M(T)=M0(T)+χ(T)*H for the magnetization. The garnet phase Gd3Fe5O12 is ferrimagnetic and showed a compensation temperature Tcomp ≈ 295 K.

The work presented in this thesis has been focus on developing the idea of mesoreactor based on mesoporous silica SBA-15. SBA-15 is a mesoporous material with highly ordered pore structure and tailorable pore sizes with narrow sizes distribution. SBA-15 has been utilized to provide reaction sites for electroless copper deposition and the support of the synthesized copper nanoparticles. Oxidation processes have been conducted in order to improve the weak ion-exchange capability of as-synthesized silica surfaces. The efficiency of oxidation processes have been studied through various oxidizing agents and time. The surface treatments of mesoporous silica have been proofed to affect the distribution of the nanoparticles. Copper nanoparticles of 5 nm with narrow size distribution have been synthesized without the use of any capping agents and are homogeneously embedded in the silica matrix.

<p>Graphene is a novel carbon material with great promise for a range of applications due to its electronic and mechanical properties. Its two-dimensional nature translates to a high sensitivity to surface chemical interactions thereby making it an ideal platform for sensors. Graphene's electronic properties are not degraded due to mechanical flexing or strain (Kim, K. S., et al. nature 07719, 2009) offering another advantage for flexible sensors integrated into numerous systems including fabrics, etc. </p><p>We have demonstrated a graphene NO2 sensor on a solid substrate (100nm SiO2/heavily doped silicon). Three different methods were used to synthesize graphene and the sensor fabrication process was optimized accordingly. Water is used as a controllable p-type dopant in graphene to study the relationship between doping and graphene's response to NO2. Experimental results show that interface water between graphene and the supporting SiO2 substrate induces higher p-doping in graphene, leading to a higher sensitivity to NO2, consistent with theoretical predications (Zhang, Y. et al., Nanotechnology 20(2009) 185504). </p><p>We have also demonstrated a flexible and stretchable graphene-based sensor. Few layer graphene, grown on a Ni substrate, is etched and transferred to a highly stretchable polymer substrate (VHB from 3M) with preloaded stress, followed by metal contact formation to construct a flexible, stretchable sensor. With up to 500% deformation caused by compressive stress, graphene still shows stable electrical response to NO2. Our results suggest that higher compressive stress results in smaller sheet resistance and higher sensitivity to NO2. </p><p>A possible molecular detection sensor utilizing Surface Enhanced Raman Spectrum (SERS) based on a graphene/gallium nanoparticles platform is also studied. By correlating the enhancement of the graphene Raman modes with metal coverage, we propose that the Ga transfers electrons to the graphene creating local regions of enhanced electron concentration modifying the Raman scattering in graphene.</p> / Dissertation

The ability to produce monomolecular coatings with well-defined structural and functional properties is of key importance in biosensing, drug delivery, and many recently developed applications of nanotechnology. Organic chemistry has proven to be a powerful tool to achieve this in many research areas. Herein, we present the synthesis of three oligo(lactosides) glycosylated in a (1 → 3) manner, and which are further functionalized with amide-linked short alkanethiol spacers. The oligosaccharides (di-, tetra-, and hexasaccharide) originate from the inexpensive and readily available lactose disaccharide. These thiolated derivatives were immobilized onto gold surfaces, and the thus formed self-assembled monolayers (SAMs) on planar gold were characterized by wettability, ellipsometry and infrared reflection–absorption spectroscopy. Further, the ability of these SAMs to stabilize gold nanoparticles in saline solutions was also demonstrated, indicating that the oligosaccharides may be used as stabilizing agents in gold nanoparticle-based assays.

Clinical hyperthermia refers to treatment of tumors by heating the lesions between 40 and 45° C. Several clinical trials have demonstrated that hyperthermia provides significant improvements in clinical outcomes for a variety of tumors, especially when combined with radiotherapy. However, its routine clinical application is still not optimal and major improvements are needed. The temperature distributions achieved are far from satisfactory and improved temperature control and monitoring are still in need of further development. The use of gold nanoparticles (GNPs) has emerged as a good method to achieve local heat delivery when combined with near-infrared (NIR) laser. GNPs have a plasmon resonance frequency that can be tuned to absorb strongly in the NIR region where tissue absorption of laser light is minimal, allowing for less tissue heating and better penetration. For further development of the technique and appropriate clinical translation, it is essential to have a computational method by which the temperature distribution within the tumor and surrounding tissue can be estimated. Previously, our group developed a technique to estimate the temperature increase in a GNP-filled medium, by taking into account the heat generated from individual GNPs. This method involved a two-step approach combining the temperature rise due to GNPs and the solution to the heat equation using the laser light as heat source. The goal of this project was to develop a one-step approach that calculates the temperature distribution using the solution to the heat equation with multiple heat source terms, the laser light, and each individual GNP. This new method can be of great use in developing a treatment planning technique for GNP-mediated thermal therapy including hyperthermia.

Adsorption-mediated self-assembly of nanoparticles at fluid interfaces, driven by reduction in interfacial energy, leads to stabilization of emulsions and foams and can be used for the bottom-up fabrication of functional nanostructured materials. Improved understanding of the parameters that control the self-assembly, the structure of nanoparticles at the interface, the barrier properties of the assembly and the rate of particle attachment and exchange is needed if such nanoparticle assemblies are to be employed for the design and fabrication of novel materials and devices. Here, I report on the use of dynamic surface tension (DST) measurements to probe the kinetics of irreversible adsorption and self-assembly of hydrophobic ethyl-cellulose (EC) nanoparticles at the air-water interface. Using thermodynamic arguments, I make a direct connection between the DST and the time-dependent surface coverage. I show that adsorption models appropriate for surfactants (e.g., Ward and Tordai model) break down for irreversible adsorption of nanoparticles, when the adsorption energy far exceeds the mean energy of thermal fluctuations (kBT) and surface blocking effects give rise to a steric barrier to adsorption. I show instead that irreversible adsorption kinetics are unequivocally characterized in terms of the adsorption rate constant and the maximum (jamming) coverage, both of which are determined on the basis of DST data using the generalized random sequential adsorption theory (RSA) for the first time. Novel accurate estimates of the adsorption energy of 42 nm and 89 nm EC nanoparticles are also provided. Coverage of the interface to the jamming limit of 91%, corresponding to a triangular lattice in 2D, is experimentally demonstrated. Colloidal solutions of EC nanoparticles are stabilized at neutral pH by electrostatic repulsive forces. Strong adsorption of these particles at an interface of like charge suggests the parallel action of attractive hydrophobic forces.

Glucose-6-phosphate (G6P) plays an important role in carbohydrate metabolism of all living organisms. Compared to the conventional analytical methods available for estimation of G6P, the biosensors having relative simplicity, specificity, low-cost and fast response time are a promising alternative. We have reported a G6P biosensor based on screen-printed electrode utilizing Prussian Blue (PB) nanoparticles and enzymes, glucose-6-phosphate dehydrogenase and glutathione reductase. The PB nanoparticles acted as a mediator and thereby enhanced the rate of electron transfer in a bi-enzymatic reaction. The Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy study confirmed the formation of PB, whereas, the atomic forced microscopy revealed that PB nanoparticles were about 25-30 nm in diameter. Various optimization studies, such as pH, enzyme and cofactor loading, etc. were conducted to obtain maximum amperometric responses for G6P measurement. The developed G6P biosensor showed a broad linear response in the range of 0.01-1.25 mM with a detection limit of 2.3 mM and sensitivity of ­63.3 mA/mM at a signal-to-noise ratio of 3 within 15 s at an applied working potential of -100 mV. The proposed G6P biosensor also exhibited good stability, excellent anti-interference ability and worked well for serum samples.

Heat shock protein 70 (HSP70) is an important health related biomarker, being implicated as an early stage cancer marker and as an indicator of cardiac health. It also has important implications in wildlife environmental monitoring, as its levels can be affected by food deprivation, elevated temperatures, and pollution. Therefore, the use of HSP70 as a biomarker is highly desirable, yet the current methods of quantifying HSP70 are time consuming, expensive, and require dedicated labs. In order to facilitate widespread use of the HSP70 biomarker, a quantification tool that can be used at the point-of-care is needed. This implies the development of a simple and inexpensive HSP70 biosensing technique that is highly sensitive and selective. Therefore, in this work a label-free HSP70 biosensor has been designed based on the optical properties of gold nanoparticles (NPs). Gold NPs exhibit a large absorbance peak in the visible spectrum due to localized surface plasmon resonance (LSPR). The peak position is dependent on the local refractive index, which can be employed as a biosensor by selectively capturing the target analyte to the NP surface. To design an LSPR HSP70 sensor, optical and fluidic simulations were developed to determine optimal NP geometries and microchannel dimensions. The results showed optimal response when using 100nmx5nm gold nanotriangles inside of a 100μmx100μm microchannel. Simulations of the sensor performance showed HSP70 detection from 0.92-4000ng/ml with a resolution of 1.1ng/ml, all of which satisfied the design requirements. An LSPR sensor was experimentally tested at the benchtop scale to prove the concept. Gold NPs were fabricated by electron beam lithography and enclosed in a polymer flow cell. For initial testing of the LSPR sensor, the NPs were functionalized with biotin for selective capture of streptavidin. Streptavidin was detected in real time over the range 55-500,000ng/ml. The use of bovine serum albumin (BSA) was shown to be necessary to block non-specific binding sites to ensure a streptavidin-specific response. The LSPR sensor was then demonstrated to detect salmon HSP70 at 4600ng/ml using its synthetic antibody. Overall, these results demonstrate that LSPR can be used to realize an HSP70 biosensor suitable for point-of-care applications.

Nanoparticle-based drug delivery systems (NDDS) have emerged as a promising strategy for formulation of anticancer drugs due to their ability to passively target solid tumors via exploitation of the enhanced permeation and retention effect. In particular, nano-sized block copolymer micelles (BCMs) have proven to be a viable delivery vehicle for hydrophobic anticancer drugs. To further enhance the specificity of BCMs towards cancer cells, extensive research has been focused on the formulation of actively targeted BCMs with tumor cell binding antigens conjugated to their surface. However, the in vivo transport of passively and actively targeted BCMs has only been studied to a limited extent. This thesis explores the potential and limitations of passively and actively targeted BCMs, as NDDS for delivery to solid tumors. The in vivo transport of BCMs at the whole body, tumor, and cellular levels is investigated in human breast cancer xenografts. Overall, active targeting of BCMs with epidermal growth factor (EGF) as the tumor cell binding antigen was not found to alter the whole body clearance of the vehicles; however, particle size had a profound effect on their pharmacokinetics and biodistribution profiles. Both passively and actively targeted BCMs exhibited heterogeneous distribution throughout solid tumors, with preferential localization in the tumor periphery and/or highly vascularized regions. In addition, the BCMs were found to exhibit impaired tumor penetration due to limited mobility and/or the binding site barrier. Although active targeting increases the in vivo BCM cellular uptake, the BCMs largely remained in the extracellular compartment, indicating that incomplete BCM delivery to all tumor cells remains as a major biological barrier. Interestingly, EGF-conjugated BCMs induced a potent bystander effect in vitro as a result of the paradoxical apoptotic effect of EGF, which has the potential to treat nearby tumor cells that do not respond directly to BCM treatment in vivo. In this way, EGF-BCMs may be beneficial for rendering the aforementioned in vivo barriers such as limited tumor penetration, as well as heterogeneity in tumor vascularization and receptor expression.