Current methods to diagnose and treat cancer often involve expensive, time-consuming equipment and materials that may lead to unwanted side effects and may not even increase a patient’s chance of survival. Thus, for a while now, a large part of the research community has focused on developing improved methods to detect, diagnose, and treat cancer on the molecular scale. One of the most recently discovered methods of cancer therapy is targeted therapy. These targeted therapies have potential to provide a patient with a form of personalized medicine because these therapies are biological molecules that specifically target other molecules involved with a cancer’s growth. Past trials using these therapeutic molecules, however, have led to controversial results, where certain patients responded better than others to the therapy for unknown reasons. Elucidating the reason behind these mixed results can be accomplished using metal nanoparticle technologies which could provide a bright signal to monitor the path that these therapeutic molecules take in vivo as well as enhance the molecule’s efficacy. Literature has shown that presenting targeting molecules in a dense manner to their target will increase these molecules’ binding affinity. This concept has been explored here to increase binding affinity of therapeutic molecules by attaching these molecules in a dense manner on the surface of gold nanoparticles, and correlating this increased affinity with therapeutic efficacy. Additionally, gold nanoparticles provide an easy surface for molecules to be functionalized on and have shown to be effective imaging, x-ray, and photothermal therapy agents. A major roadblock to using these gold nanoparticles clinically is their non-degradability and thus potential to cause long-term negative side effects in vivo. A platform for developing biodegradable gold nanoparticles is also explored here to take advantage of the gold nanoparticles’ excellent imaging and drug delivery capabilities while still allowing them to be used safely in the long term. / text

This research focuses on the microwave properties of nanoparticles for use as contrast and hyperthermia agents. Currently, visible light is used for irradiation of nanoparticles as hyperthermia agents. Additionally, visible/Near-infrared light is used for photoacoustic tomography (PAT) imaging. Compared to optical wavelengths, frequencies in microwave range transmit through tissue with high penetration depth . Thus, deep cancerous cells and malignant tissue may be treated and imaged. These nanoparticles could enable the use of a hybrid microwave/acoustic technique known as thermoacoustic tomography. Here, quantitative measurements of the heat generation in super paramagnetic iron oxide nanoparticle (SPIONs), gold nanoparticles (AuNPs), and gold nanoclusters (AuNCs) induced by microwave energy at 3 GHz, are presented and compared. Based on our experiments, SPIONs are the most efficient nanoparticles for microwave heating. Very high concentrations of SPIONs are able to convert microwave energy into heat about 22° C more than DI-water. AuNPs, which support plasmon resonances, do not provide heat under microwave irradiation as predicted by our computational analysis based on Mie Theory. AuNCs are a new form of ultra-small (<2.5 nm) AuNPs which do not support plasmonic resonances and have supra-molecular properties such as sub-conduction band transitions. Interestingly, AuNCs have the potential to absorb microwave energy and may provide an alternative to SPIONs. These nanoparticles had not yet been studied before in this frequency region. In addition, the absorption coefficient of nanoparticles were calculated using complex permittivity data from a dip probe kit and a Vector Network Analyzer (VNA) in a broad band range from 500 MHZ to 10 GHz. This method allows identification of best frequency region with highest penetration depth. In the last step, the nanoparticles with different concentrations were tested as exogenous contrast agents in a Thermoacoustic Tomography (TAT) system. TAT utilizes the penetration depth of microwave energy while producing high resolution images through acoustic waves. The addition of an exogenous contrast agent improves image quality by more effectively converting microwave energy to heat. The experiment reveals that the time resolved thermoacoustic signal (TA) from SPIONs is stronger than AuNPs and AuNCs and thus, the image contrast produced by SPIONs is stronger than the two other aforementioned nanoparticles.

Iron oxides and arsenic are prevalent in the environment. With the increase interest in the use of iron oxide nanoparticles (IONPs) for contaminant remediation and the high toxicity of arsenic, it is crucial that we evaluate the interactions between IONPs and arsenic. The goal was to understand the environmental behavior of IONPs in regards to their particle size, aggregation and stability, and to determine how this behavior influences IONPs-arsenic interactions. A variety of dispersion techniques were investigated to disperse bare commercial IONPs. Vortex was able to disperse commercial hematite nanoparticles into unstable dispersions with particles in the micrometer size range while probe ultrasonication dispersed the particles into stable dispersions of nanometer size ranges for a prolonged period of time. Using probe ultrasonication and vortex to prepare IONPs suspensions of different particle sizes, the adsorption of arsenite and arsenate to bare hematite nanoparticles and hematite aggregates were investigated. To understand the difference in the adsorptive behavior, adsorption kinetics and isotherm parameters were determined. Both arsenite and arsenate were capable of adsorbing to hematite nanoparticles and hematite aggregates but the rate and capacity of adsorption is dependent upon the hematite particle size, the stability of the dispersion and the type of sorbed arsenic species. Once arsenic was adsorbed onto the hematite surface, both iron and arsenic can undergo redox transformation both microbially and photochemically and these processes can be intertwined. Arsenic speciation studies in the presence of hematite particles were performed and the effect of light on the redox process was preliminary quantified. The redox behavior of arsenite and arsenate were different depending on the hematite particle size, the stability of the suspension and the presence of environmental factors such as microbes and light. The results from this study are important and have significant environmental implications as arsenic mobility and bioavailability can be affected by its adsorption to hematite particles and by its surface mediated redox transformation. Moreover, this study furthers our understanding on how the particle size influences the interactions between IONPs and arsenic thereby clarifying the role of IONPs in the biogeochemical cycling of arsenic.

In this study, a magnetic nanomaterial was used for the binding of anionic arsenic species from contaminated groundwater. Iron oxide (Fe3O4) magnetic nanoparticles (NPs) and the surface modified Fe3O4 NPs with 3-aminopropyl-triethoxysilane (3-APTES), Trisodium citrare (TSC) and Chitosan were synthesized with the co-precipitation method. Structural characterizations showed that the four kinds of NPs had different sizes an average particle range size of 15-20 nm was observed with Transmission Electron Microscopy. X-ray diffraction was used to identify the crystalline structure of synthesized Fe3O4 and surface modified NPs. Molecular structure and functional groups present in synthesized magnetic NPs Fe3O4 were identify with infrared analysis. The synthesized Fe3O4 NPs and surface coated NPs were used for determine the binding capacity of Arsenic ions from the synthetic groundwater. The binding of As(III) increased as the dissolved As(III) concentration increased in the solution. From the experiments it was found chitosan-coated NPs are best than other coated and uncoated NPs for arsenite removal from the solution. It was found that if only As(III) ions were present in the water without other anions and cations the binding capacity of the magnetic NPs is very high. The binding capacity of As ions was decreased with presence of other anions and cations in the groundwater because they interfere with arsenic binding sites which presence on the magnetic NPs.

No description available.

The capability of precisely controlling the kinetics of therapeutic delivery at the optimal location and rate for a given patient would have great potential to improve health and well-being in a range of current drug therapies (insulin, chemotherapeutics, vaccines, etc.). Indeed, if successfully developed, locally administered injectable drug delivery vehicles capable of remotely-triggered release would be the gold standard for many treatments. Multiple injectable nanocomposites have been investigated for this purpose that are generally comprised of a thermosensitive polymeric material and superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs generate heat when exposed remote alternating magnetic fields (AMFs), and the transfer of this heat to thermosensitive polymers can be used to control the release of therapeutics. Ideally, these systems would be capable of returning to their original state and basal release rate when the external AMF trigger is removed. Several novel injectable nanocomposite materials that explore interactions between SPIONs and thermosensitive polymers to mediate drug release, from the macroscale to the nanoscale, were developed and demonstrated to be capable of remotely-triggered, AMF-mediated enhanced release. The macroscale magnetic nanocomposites have thermosensitive hydrogel and/or microgel components that regulate release based on the heat produced from SPIONs in response to an external AMF. On the millimeter-scale, a microinjection system capable of producing thermosensitive hydrogel beads that could potentially incorporate SPIONs is described. On the nanoscale, nanoparticles with a glass transition temperature and thermosensitive microgels are combined with SPIONs and investigated for their remote, AMF-mediated release characteristics. The engineered macroscale and nanoscale systems are capable of up to ~4:1 and ~7:1 enhancements in release due to an AMF application, respectively, compared to the basal release rate. Collectively, these nanocomposites represent a promising stride towards improved remote-actuation of drug release and a stepping stone for future attempts at precisely controlling the site and kinetics of drug release. / Thesis / Doctor of Philosophy (PhD) / This thesis focuses on the development of nanocomposite materials that can be injected into a specific location in the body and deliver therapeutic drugs by a remote-controlled process. These nanocomposites are composed of magnetic particles and polymers that respond to changes in temperature. The combination of these materials results in nanocomposites that can change their properties in response to specific magnetic fields to switch from releasing drug slowly (or not at all) to releasing drug quickly on demand. The changes are fully reversible and solely depend on whether the external magnetic field is switched on or off. These novel systems offer an alternative to therapies that require frequent injections, such as insulin for diabetes, or therapies that need the drug to be released in very precise locations, such as cancer treatments, and could improve the safety, reduce the risk of side effects, and lower the cost of many medical treatments.

Yes / The gadolinium-doped iron oxide nanoparticles (GdIONP) with greater specific power adsorption rate (SAR) than Fe3O4 was developed and its potential application in tumour therapy and particle tracking were demonstrated in transgenic adenocarcinoma of the mouse prostate C1 (TRAMP-C1) tumours. The GdIONPs accumulated in tumour region during the treatment could be clearly tracked and quantified by T2-weighted MR imaging. The therapeutic effects of GdIONP-mediated hyperthermia alone or in combination with radiotherapy (RT) were also evaluated. A significant increase in the tumour growth time was observed following the treatment of thermotherapy (TT) only group (2.5 days), radiation therapy only group (4.5 days), and the combined radio-thermotherapy group (10 days). Immunohistochemical staining revealed a reduced hypoxia region with vascular disruption and extensive tumour necrosis following the combined radio-thermotherapy. These results indicate that GdIONP-mediated hyperthermia can improve the efficacy of RT by its dual functions in high temperature (temperature greater than 45 °C)-mediated thermal ablation and mild-temperature hyperthermia (MTH) (temperature between 39 and 42 °C)-mediated reoxygenation.

Two different iron oxide nanofluids were tested for heat transfer properties in industrial cooling systems. The nanofluids either had 30 nm particles with a wide size distribution to include particles greater than 1 micrometer or 15 nm particles with greater than 95% of the particles less than 33 nm. Calorimetry and thermal circuit modeling indicate that the 15 nm particle ferrofluid enhanced heat capacity. The smaller particle ferrofluid also demonstrated up to a 39% improvement in heat transfer, while the larger particle ferrofluid degraded the heat transfer performance. Particles from the larger particle ferrofluid were noted as settling out of a circulating system and therefore not participating in the bulk fluid properties. Application of 0.32% 15nm particles in an open cooling system improved cooling tower efficiency by 7.7% at a flow rate of 11.4 liter per minute and improved cooling tower efficiency by 3.3% at a flow rate of 22.7 liter per minute, while applying 0.53% 15 nm particles also improved cooling tower efficiency but was less effective than the lower concentration.

Les nanoparticules de fer manufacturées (NPs-Fe) sont des matériaux de taille nanométrique dont l’utilisation s’est, depuis peu, étendue à des domaines environnementaux. Leur dispersion dans les milieux aqueux et solides, et leurs interactions avec le vivant soulèvent toutefois encore de nombreuses questions. Dans la première partie de cette étude, nous conduisons un travail approfondi de caractérisation des NPs-Fe et précisons comment ces propriétés sont impliquées dans les processus contrôlant la stabilité colloïdale puis la réactivité chimique (capacité d’adsorption du cuivre) des NPs-Fe en solution aqueuse. Des modifications à la fois surfaciques et cristallochimiques sont appliquées afin de mettre en évidence le rôle clés de la chimie de surface des NPs-Fe. Dans cette étude, il est montré que les acides humiques limitent l’agrégation des NPs-Fe et procurent des sites d’adsorption pour les métaux. Les conditions physico-chimiques du milieu s’avèrent également jouer un rôle crucial. Le pH modifie notamment la charge de surface des NPs-Fe et les forces d’interactions électrostatiques qui en résultent. Dans un deuxième temps, nous étudions les interactions entre les NPs-Fe et les végétaux, en solution puis dans un sol. Après 63 et 57 jours, les mesures de susceptibilité magnétique montrent que les NPs-Fe s’accumulent au niveau des racines avant d’être transloquées, en moindre quantité, dans les parties aériennes des plantes. La réponse des plantes à l’exposition aux NPs-Fe se traduit par une augmentation de la biomasse végétale et des teneurs en chlorophylles et une diminution de la peroxydation lipidique. / Engineered Iron Oxide Nanoparticles (IONPs) are specific nanoscale materials that have recently been used into wide environmental applications. The dispersion of IONPs into soils and waters, as well as their interactions with living organisms, raise many scientific issues. The first part of this work is intended to provide a thorough characterization of IONPs in aqueous solution, from their intrinsic physico-chemical properties to their colloidal behavior and chemical reactivity. Surface modifications are applied to evidence the key role of surface chemistry towards most interactions IONPs encounter. In particular, humic acid reduce NPs-Fe aggregation and display a high adsorption capacity for trace metals, especially copper (Cu).On the other hand, the pH of the solution play a critical role towards NPs-Fe interactions. Depending on the pH, the surface charge of the particles are modified and hence pH is involved in the electrostatic forces that drive the particles aggregation state and contribute to metal adsorption. The second part of the study is focused on the interactions occurring with IONPs in presence of plants. Several experiments are conducted in aqueous solution and in soil columns to precise the impacts of IONPs on the growth medium and to assess the effects of IONPs on plants. Results (magnetic susceptibility) show that IONPs manage to penetrate the roots of beans and sunflower plants (57 and 63 days-old) and that they are translocated to the aerial parts in low amounts. Plants respond to IONPs penetration by increasing the plant biomass and the chlorophyll contents and by decreasing the lipid peroxidation.

L’avènement des nanotechnologies engendre une exposition accrue de l’homme aux nanomatériaux, représentant un risque d’un genre nouveau. A cet égard un grand nombre de recherches porte sur l’étude de leur toxicité. Néanmoins, les questions de dégradation et transformation des nanoparticules dans l’organisme sont encore peu abordées. Des études effectuées au laboratoire ont montré qu’après injection de nanoparticules d’oxyde de fer in vivo, celles-ci sont confinées dans les lysosomes où elles sont dégradées. Une partie de mes travaux de thèse se sont concentrés sur une voie possible de métabolisation des produits de dégradation issus de nanoparticules d’oxydes de fer par l’intermédiaire d’une protéine intervenant dans le métabolisme du fer, la ferritine. Nous avons élaboré plusieurs stratégies afin de détecter et de suivre le transfert de métaux vers la ferritine. Ces travaux ont permis de mettre en évidence un processus de prise en charge des produits de dégradation des nanoparticules d’oxyde de fer à l’échelle moléculaire. Une seconde partie de mes travaux ont été consacré au suivi des produits issus de la dégradation des nanoparticules d’oxyde de fer à l’échelle de l’organisme. La haute concentration endogène en fer rendant impossible ce suivi, une stratégie consistant à marquer les nanoparticules de fer avec un isotope du fer, le 57Fe, a permis de suivre les dynamiques de circulation des produits de dégradation in vivo sur une période de six mois. Nous avons également effectué un double marquage des nanoparticules, du cœur inorganique ainsi que de leur enrobage afin de caractériser leur intégrité in vivo / With the advent of nanotechnology, the exposure of humans to nanomaterials increased, representing a risk of a new kind. Although the potential toxicity of such nanomaterials is extensively studied, their long term fate, biotransformation and degradation in the organism are still poorly understood. It was demonstrated earlier in the laboratory, that after intravenous injection, iron oxide nanoparticles undergo local intracellular degradation within lysosomes. In this context, we are interested in the fate of by products from iron oxide nanoparticles. Part of my thesis has focused on a possible pathway for metabolizing these degradation products through a protein involved in iron metabolism, the ferritin. We first studied, in solution, the degradation processes of iron oxide nanoparticles in the presence of these proteins as well as the iron transfer processes from nanoparticles to ferritin. The difficulty is the high concentration of endogenous iron which makes impossible to demonstrate these in vivo transfers. Thus, we have developed a strategy, using doped iron oxide nanoparticles with a scarce element in the organism, to track these phenomena in vivo. This work highlighted a possible mechanism of biological recycling, remediation and detoxification of nanoparticles mediated by endogenous proteins at the molecular scale. A second part of my work was devoted to develop a multi-scale method to study the life cycle of metal oxide nanoparticles and their by products in organism. The main challenge is to differentiate iron stemming from the nanoparticles from the endogenous iron. This specific tracking problem is routinely encountered in geochemical studies and solved by labelling the target material with minor stable isotopes. Therefore, iron oxide nanoparticles enriched in the minor stable isotope 57Fe were synthetized and injected intravenously in mice to follow dynamic circulations of iron oxide nanoparticles and their byproducts. We have also labelled the coating to track the nanoparticles integrity in mice over a period of six month