Abstract Our overall research goal is to synthesize a water-soluble, bio-absorbable theranostic nanoparticle (NP) that will improve diagnostic and therapeutic efficacy for cancer. Such theranostic nanoparticles are composed of carbon dots (CDs), conjugated with a targeting agent through a non-cleavable peptide bond; and an anticancer drug Doxorubicin (DOX) using an acid-labile hydrazine linkage for targeted delivery and bio-imaging functions. Recent studies have shown that Carbon dots (CDs) are of interest in biological applications due to their unique properties such as inherent fluorescence, extremely high biocompatibility, and facile synthetic route. The large surface area and multiple surface functionalities make CDs versatile platforms to conjugate with other moieties, including therapeutic agents or targeting agents. The target agents, such as folic acid (FA), are proposed to be permanently linked with CDs to improve the target specificity of the tumor cells. Folic acid is used as a targeting agent as it is a water-soluble, low molecular weight vitamin as it plays an essential role in cell survival and binds with high affinity to the folate receptor (FR) – a membrane-anchored protein that is a cancer biomarker. The multimodal nano-platforms of CDs can also facilitate the delivery the anticancer drugs. The anticancer drug is attached by a cleavable linker that can release the drug inside the tumor cell. We will use the cytotoxic chemotherapeutic agent doxorubicin (DOX) as an example. One series of CDs, FA-CD and FA-CD-DOX, are successfully prepared in the lab. The UV-vis and Fluorescence spectra of the sample was investigated and compared. The concentration of each part in nanoparticles are calculated. The final Drug Load Content (DLC) and Drug Load Efficiency (DLE) are also calculated and compared with the literature. Another series of FA-CD-DOX will be prepared and compared. The characterization of the diagnostic and therapeutic potential of the NP particles will be carried out in the pharmaceutical department.

The use of heterogeneous catalysis is well established in chemical synthesis, energy, and environmental engineering applications. Supported Pt nanoparticles have been widely reported to act as catalysts in a vast number of chemical reactions. In this report, the performance of Pt/ZrO2 nanocatalyst for the decomposition of methanol, ethanol, 2-propanol, and 2-butanol is investigated. The potential of each alcohol for the production of H2 and other relevant products in the presence of a catalyst is studied. All the alcohols studied show some decomposition activity below 200°C which increased with increasing temperature. In all cases, high selectivity towards H2 formation is observed. With the exception of methanol, all alcohol conversion reactions lead to catalyst deactivation at high temperatures (T > 250°C for 2-propanol and 2- butanol, T > 325°C for ethanol) due to carbon poisoning. However, long-term catalyst deactivation can be avoided by optimizing reaction conditions such as operating temperature. In addition, the performance of Pt/γ-Al2O3 is evaluated in the oxidation of 2-propanol. Pt nanoclusters of similar size (~1 nm diameter) but different structure (shape) were found to display distinctively different catalytic properties. All the systems studied achieve high conversion (~ 90%) below 100°C. However, flatter particles display a lower reaction onset temperature, demonstrating superior catalytic performance. Acetone, CO2, and water are generated as products indicating that both partial and complete oxidation are taking place. A number of techniques including AFM, XPS, TEM, HAADF-TEM, XAFS as well as packed-bed reactor experiments were used for sample characterization and evaluation of catalytic performance.

Catalysis technologies are among the most important in the modern world. They are instrumental in the realization of a variety of products and processes including chemicals, polymers, foods, pharmaceuticals, fuels, and fuel cells. As such, interest in the catalysts that drive these processes is ongoing, and basic research has led to significant advances in the field, including the production of more environmentally friendly catalysts that can be tuned at the molecular/atomic level. However, there are many factors which influence the performance of a catalyst and many unanswered questions still remain. The first part of this work is concerned with the factors that influence the catalytic properties (activity, selectivity, and stability) of supported Pt and Pt-M nanoparticles (NPs). These factors are a synergistic combination of size, composition, support, oxidation state, and reaction environment (i.e. adsorbates, temperature, pressure, etc.). To probe the catalytic properties of complex and dynamic NP systems we have used MeOH decomposition and oxidation reactions, each of which has significant environmental and economic potential. We have given some emphasis to the state of NP oxidation, and with the aid of X-ray photoelectron spectroscopy (XPS) and temperature programmed desorption (TPD), have followed the formation and temperature-dependent evolution of oxide species on Pt NPs. Further, we have explored how these species behave under the conditions of our probe reactions using a packed-bed mass flow reactor coupled to a quadrupole mass spectrometer (QMS). To carry out our investigations we exploit a NP synthesis method which is rather novel to nanocatalysis, micelle encapsulation. Since most available experimental techniques give information on ensemble averages, control over size distributions in NP samples is critical if unambiguous results are to be obtained. Micelle encapsulation allows us this control with several unique, inherent iv advantages. It is to this end that micelle encapsulation has allowed us to probe the detailed structure of small (~1 nm), supported, Pt NPs with extended X-ray absorption fine structure spectroscopy (EXAFS). Furthermore, we were able to explore experimentally, for the first time, the vibrational density of states (VDOS) of supported, isolated, monodispersed, mono and bimetallic NP systems via nuclear resonant inelastic X-ray scattering (NRIX). These synchrotron-based techniques (EXAFS, NRIXS) rely heavily on the monodispersity of the NP ensemble for reliable information

One of the most common methods of drug delivery to the anterior segment of the eye is topical application of an ophthalmic solution or suspension. The ophthalmic solution may contain various particle based materials, such as nanoparticles, to control the rate at which the drug is delivered to the eye. The issue with this delivery method is that there are several barriers at the front of the eye. These barriers, which include a high tear film turnover rate and induced lacrimation, reduce the residence time of the drug at the site of administration and result in 95% of the administered drug being removed systemically or via nasolacrimal drainage. Additionally, once the material has left the target location it should degrade in a controlled manner so that it can be safely removed from the body. The current work focuses on the development of polymeric nanoparticles that can serve as a delivery system for ophthalmic drugs. The material proposed for the nanoparticle synthesis is poly(2-hydroxyethyl methacrylate (HEMA)), a polymer with a long history of ophthalmic compatibility. The original nanoparticle formulation was modified to allow for degradation and mucoadhesion. To facilitate degradation, a crosslinker which degrades under ocular conditions was incorporated. A mucoadhesive polymer was incorporated into the particles to enhance the residence time of the particles at the front of the eye. Size and morphology analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles were comprised of poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA) was successfully incorporated. Degradation of nanoparticles containing N,N’-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity, measured by absorbance, and through transmission electron microscopy (TEM). Based on zeta potential results, poly(HEMA, BAC, 3AAPBA) samples C3 to C6 were found to be mucoadhesive. Dexamethasone release from poly(HEMA) nanoparticles and poly(HEMA, BAC, 3AAPBA) nanoparticles, loaded with efficiencies of 15.0% ±1.4% and 5.3% ±0.4%, resulted in rate constants of 0.001 and 0.002, and release exponents of 0.607 and 0.586, respectively. The toxicity of the nanoparticles was tested by incubation in the presence of human corneal epithelial cells (HCEC). In the presence of the poly(HEMA), poly(HEMA, BAC), and poly(HEMA, BAC, 3AAPBA) samples the HCEC viability was found to be 123.6% to 182.5%, 88.5% to 111%, and 69.8% to 85.1%, respectively. The viability of HCEC after incubation with poly(HEMA) was significantly higher compared to poly(HEMA, BAC) samples with a dilution factor of 0 and 2. Additionally, the HCEC viability in the presence of poly(HEMA, BAC, 3AAPBA) sample C6 was found to be significantly lower compared to samples C2 and C3 from Table 3. The previously summarized results suggest that the poly(HEMA) based nanoparticles produced in this work have the potential for drug delivery to the front of the eye. / Thesis / Master of Applied Science (MASc)

In recent decades, a variety of nanoparticle drug delivery systems (NP DDS) – nanometer-scaled materials physically or covalently interacting with therapeutics – has been developed to overcome biological barriers, improve the half-life, reduce toxicity, and improve the efficacy of conventional drug delivery. However, many NP DDS fail to translate to the clinic. While this is in part due to immense heterogeneity within many disease types across individuals, the conflicting size and surface chemistries required in the “drug delivery pathway” (i.e. to avoid the clearance mechanisms and unintended tissues in the body, then to reach and specifically enter target tissues) also pose a significant challenge. Recent advances in the field of drug delivery have created size- and surface-switching nanoparticles that overcome biological barriers. For example, large (100 – 200 nm) NPs are adequate at evading corporeal defense mechanisms, while small (< 50 nm) NPs can actively enter cancerous tissue. Further, release profiles of drug-loaded NP DDS must be tailored to stay within a narrow therapeutic window to prevent toxic effects. This thesis highlights the synthesis of “nanoassemblies”, an NP DDS that contains small, drug-loaded starch nanoparticles (SNPs) within a larger nanogel matrix. Nanoassemblies are chemically tuned to reach specific targets via different administration routes (notably, cancerous tissues via systemic administration and brain tissue via intranasal administration). Furthermore, therapeutic-loaded SNPs are released under endogenous (pH, redox) or exogenous (ultrasound) stimuli for disease-specific release kinetics, allowing for deeper penetration into tumor cores or through the nose-to-brain pathway as required. Both the physicochemical characterization of these nanoassemblies as well as in vitro and in vivo experiments have been performed to assess the efficacy of nanoassemblies in biological systems and how they may provide performance improvements over non-assembled SNPs. As such, nanoassemblies show great promise in overcoming complex biological barriers to ultimately improve drug delivery in clinical applications. / Thesis / Doctor of Philosophy (PhD) / Using drugs to treat diseases is not always effective: the drug often does not work or comes with many side effects. A combination of factors prevents promising drugs from working. Most often the drug is either (partially or fully) removed from the body before it reaches the disease, or it improperly enters healthy tissue to cause undesirable responses. Previous research has shown that if drugs are put into nanoparticles, the nanoparticles can better deliver the drug to the correct target. However, conflicting sizes are needed to travel through different parts of the body, making nanoparticle-based drug delivery only of limited effectiveness in humans. This thesis aims to address these issues by creating “nanoassemblies” – nanoparticles with smaller, drug-containing nanoparticles inside of them – that overcome the typical issues with drug delivery. Nanoassemblies are able to switch their size to better reach the target tissue, ultimately leading to more effective and safe treatments.

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Nanoparticles (NPs) have attracted considerable attention in the field of separation science, especially in filtration studies for direct membrane integrity tests, investigating pore-size distribution, and their potential to be used as surrogates for various types of viruses encountered in water treatment and bioprocessing applications. Although the effect of adding surfactants to stabilize NP suspension have been explored for a number of different applications, there is significant variation in the amounts and types of surfactants used in filtration studies. This study used three different sizes (59, 188, and 490 nm) of fluorescent polystyrene nanoparticles (PNPs) to mimic the length, width, and aggregates of Rhabdovirus Maraba, a bullet-shape envelope virus. The PNPs were suspended in solutions with varying concentrations of the nonionic surfactant Tween 20 (0.0005% to 0.1% (v/v) in the carbonate buffer feed solution) and were tested in constant-flux filtration studies using two commercial microfiltration (MF) membranes (Durapore PVDF and MiniSart PES) with 0.22 micron pore size ratings. Results clearly demonstrate that adding a nonionic surfactant to a PNP solution will cause a shift from full retention to complete transmission during the dead-end MF of PNPs that are smaller than the pore size of an MF membrane. In a separate study, in order to have a better resemblance of virus particles in terms of surface properties, 188 nm PNPs were coated with different (lysozyme, α -lactalbumin and bovine serum albumin) proteins in order to gain similar surface properties to actual virus particles. Filtration results with one type of commercial MF membranes (Durapore PVDF) 0.22 μm pore size, clearly indicate that the transmission behavior of PNPs strongly depends on their surface properties. PNPs fully covered with BSA and α–lactalbumin could completely pass through the membranes while uncovered or partially covered PNPs resulted in no transmission or partial transmission. / Thesis / Master of Applied Science (MASc) / Nanoparticles (NPs) has been employed enormously in various applications for a variety of purposes. One of the areas that have been greatly influenced by NPs, is the field of separation science. In the pharmaceutical industry, purification of therapeutics involves a sequence of filtration and in this step, therapeutic virus filtration, sterile filtration, in particular, have been poorly studied. There is also a growing interest in the use of engineered viruses for cancer treatment due to its magnificent implication on human health. However, there are significant challenges in running filtration experiments with pathogenic substances. Therefore it has been determined that a detailed and comprehensive study of sterile filtration of virus-size NPs can benefit this area. In this work, fluorescently-labeled NPs has been used as surrogates of oncolytic viruses to extract fundamental aspects affecting the transmission of virus-sized particles through commercial microfiltration sterilizing grade membranes.

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