Rozprawy doktorskie na temat „Iron nanoparticles”

Nanoscale zero-valent iron (NZVI) particles and iron cross-linked alginate (FCA) beads were successfully used for the first time for phosphate removal and recovery. NZVI was successfully used for phosphate removal and recovery. Batch studies indicated a removal of ~96 to 100% phosphate in 30 min (1, 5, and 10 mg PO43--P/L with 400 mg NZVI/L). Phosphate removal efficiency by NZVI was 13.9 times higher compared to Microscale ZVI (MZVI) particles. The successful rapid removal of phosphate by NZVI from aqueous solution is expected to have great ramification for cleaning up nutrient rich waters. The presence of sulfate, nitrate, and humic substances and the change in ionic strength in the water marginally affected phosphate removal by NZVI. A maximum phosphate recovery of ~78% was achieved in 30 min at pH 12. Novel iron cross-linked alginate (FCA) beads were synthesized, characterized and used for phosphate removal. The beads removed up to 37-100% phosphate from aqueous solution in 24 h. Freundlich isotherm was found to most closely fit with experimental data and the maximum adsorption capacity was found to be 14.77 mg/g of dry beads. The presence of chloride, bicarbonate, sulfate, nitrate, and natural organic matters in aqueous solution did not interfere in phosphate removal by FCA beads. The phosphate removal efficacy FCA beads was not affected due to change in pH (4-9). Nanosacle zero-valent iron (NZVI) and iron cross-linked alginate beads were also tested for phosphate removal using actual wastewater treatment plant effluent and animal feedlot runoff. The FCA beads could remove ~63% and ~77% phosphate from wastewater and feedlot runoff in 15 min, respectively. Bioavailability of phosphate was examined using algae and higher plants. Phosphate and iron bioavailability of the NZVI sorbed phosphate was examined by supplying spent particles (NZVI with sorbed phosphate) to Tyee Spinach (Spinacia oleracea) and algae (Selenastrum capricornutum). Results revealed that the phosphate was bioavailable for both the algae and spinach. Also, presence of the nanoparticles enhanced the algae growth and plant growth and increases in biomass and plant length were observed. Iron (from spent NZVI) was found to be bioavailable for spinach.

El trabajo de investigación se ha desarrollado conjuntamente en el Instituto de Ciencia de Materiales de Barcelona (ICMAB-CSIC) y en el Instituto de Investigación del Hospital Universitario Vall d’Hebron (VHIR) en Barcelona. El trabajo se enmarca dentro del contexto tanto de nanomateriales como de nanomedicina. El objetivo principal de la tesis doctoral es desarrollar materiales para terapias no invasivas encaminadas a potenciar la regeneración de vasos sanguinos después de un evento isquémico. Para ello se han utilizado nanopartículas magnéticas de oxido de hierro como instrumentos de visualización (“imaging” por resonancia magnética) y de acumulación de proteínas/células en tejidos específicos bajo la influencia de un campo magnético externo. Se han desarrollado dos estrategias: la primera introduciendo las nanopartículas magnéticas en células endoteliales progenitora y la segunda en nanocápsulas poliméricas junto a un factor de crecimiento vascular. La tesis está estructurada en seis capítulos: CAPÍTULO 1 Las nanopartículas superparamagnéticas de óxido de hierro (SPIONs) son conocidas en diagnosis clínico por utilizarse como agentes de contraste que permiten la visualización de los tejidos a través de resonancia magnética (MRI). El capítulo contiene una breve introducción a la nanotecnología y una presentación de las características magnéticas de los materiales. Además contiene una revisión de los métodos de síntesis de las nanopartículas superparamagnéticas de oxido de hierro. CAPÍTULO 2 Describe la síntesis de nanopartículas superparamagnéticas de oxido de hierro mediante dos técnicas: descomposición térmica y microonda. Ambos métodos nos permiten de obtener partículas monodispersas con tamaño inferior a 20 nm y con excelentes propiedades magnéticas. Se ha logrado estabilizar las partículas en agua y en distintos medios celulares mediante estabilizantes iónicos (hidróxido de tetrametilamonio y sodio citrato). CAPÍTULO 3 La isquemia cerebral se define como la obstrucción de arterias intracraneales, debida a trombos o émbolos, que producen una lesión en los tejidos no perfundidos por la sangre. La regeneración y reparación del tejido cerebral basadas en la mejora de la angiogénesis endógena podría convertirse en realidad en un futuro próximo, al haberse identificado células progenitoras endoteliales (EPCs) en individuos adultos. Las EPCs son células que pueden inducir neo-vascularización y/o remodelación de vasos mediante liberación de factores angiogénicos. Nuestro objetivo es potenciar la acción terapéutica de las EPCs guiándolas a áreas específicas del cerebro con un campo magnético externo para potenciar la regeneración cerebral después de un ictus. En este capítulo se describen los experimentos in vitro de marcaje celular, toxicidad y funcionalidad de células. Además se describe un experimento in vivo con modelos animales demostrando la acumulación de EPCs magnetizadas en la zona del cerebro en la que se aplicó un campo magnético externo. CAPÍTULO 4 Otra estrategia que se ha investigado consiste en encapsular factores de crecimientos junto con las nanopartículas magnéticas (SPIONs) en nanocápsulas biodegradables de polímero de ácido poli(D,L-láctico-co-glicólico) (PLGA), para que éstas puedan guiarse a la lesión cerebral mediante la aplicación de un campo magnético externo. Durante los meses de estancia en el grupo de la Ecole de Pharmacie Genève-Lausanne (EPGL) se empezó la síntesis de nanocápsulas poliméricas con SPIONs y proteínas modelos. Este capítulo describe la síntesis y las caracterizaciones de las nanocápsulas obtenidas. CAPÍTULO 5 Conclusiones: se detallan los resultados más importantes obtenidos en esta tesis. En la primera parte se evidencian los siguientes resultados: 1. Se han sintetizado nanopartículas de óxido de hierro biocompatibiles y con las características adecuadas para la terapia celular; 2. Se ha realizado un marcaje no tóxico de células endoteliales progenitoras con SPIONs. Además se han reportado diferentes eficiencias de marcaje celular dependiendo del tipo de EPCs (early- y outgrowth). También se ha evidenciado que la eficiencia del marcaje celular puede variar utilizando diferentes condiciones de tiempo de incubación, de concentración de SPIONs y de agregación de partículas en los medios cultivos. Aún así, no se ha reportado ningún cambio significativo en la capacidad de tubulogénesis (formación de conexiones inter-celulares) ni de migración en población outgrowth de células endoteliales progenitoras marcadas con SPIONs; 3. Se ha detectado un aumento en la liberación de factores de crecimiento angiogénicos en células outgrowth marcadas con SPIONs respecto a células outgrowth no marcadas; 4. En un estudio preliminar in vivo en ratones, se ha demostrado con éxito la migración y acumulación de células endoteliales progenitoras (poblaciones early), marcadas con SPIONs, en la zona del celebro próxima a la aplicación del campo magnético externo. En la segunda parte del trabajo de tesis se ha conseguido: 1. La síntesis de nanocápsulas de polímero biodegradable de ácido poli(D,L-láctico-co-glicólico), mediante un proceso de doble emulsión, con tamaños de partícula de 200 nm adecuadas para la administración sistémica; 2. Co-encapsulación de SPIONs y factor de crecimiento vascular endotelial (proteína comercial, recombinant human VEGF165) con buena eficiencia. 3. La proliferación de células endoteliales potenciada por la actividad biológica de VEGF165 encapsulado. CAPÍTULO 6 Contiene el curriculum del autor y los trabajos publicados durante el periodo de doctorado.
The research was developed at the Institute of Materials Science of Barcelona (ICMAB-CSIC) and the Research Institute at Hospital Vall d'Hebron (VHIR) in Barcelona. The main objective of the thesis is to develop materials for non-invasive therapies to promote blood vessel regeneration after an ischemic event. For that we used iron oxide magnetic nanoparticles for imaging (through Magnetic Resonance Imaging) and accumulation of proteins / cells into specific tissues under the influence of an external magnetic field. Two strategies have been developed: the first one by introducing magnetic nanoparticles in endothelial progenitor cells (EPCs) and the second one into polymeric nanocapsules together with a vascular growth factor. The thesis is organized in six chapters: CHAPTER 1 Superparamagnetic iron oxide nanoparticles (SPIONs) are known for their use in clinical diagnosis as contrast agents allowing the visualization of tissues through magnetic resonance imaging (MRI). The chapter contains a brief introduction to nanotechnology and a presentation of the magnetic properties of the materials. It also contains a review of the most common synthetic methods used to obtain superparamagnetic iron oxide nanoparticles. CHAPTER 2 In this chapter is described the synthesis of superparamagnetic iron oxide nanoparticles using two techniques: thermal decomposition and microwave assisted sol-gel route. Both methods allow to obtain monodisperse particles with size less than 20 nm and excellent magnetic properties. Particles have been successfully stabilized in water and different cell media by ionic stabilizers (tetramethylammonium hydroxide and sodium citrate). CHAPTER 3 Cerebral ischaemia is defined as the blockage of cerebral arteries, due to a thrombus or embolus, which produce tissue damage in the zone not perfused with blood. Brain tissue regeneration and repair, based on the improvement of endogenous angiogenesis, could become reality in the near future having identified endothelial progenitors (EPCs) cells in adults. The EPCs are cells that can induce revascularization and / or remodeling of blood vessels by release of angiogenic factors. Our goal is to enhance the therapeutic action of EPCs guiding them toward specific areas of the brain with an external magnetic field to enhance regeneration after cerebral stroke. Experiments of in vitro cell labeling, cell toxicity and functionality are described in this chapter. In addition we showed an in vivo experiment using animal models to demonstrate the accumulation of magnetized EPCs in the brain under a magnetic field due to an external magnet implantation. CHAPTER 4 Another strategy is to encapsulate growth factors together with magnetic nanoparticles (SPIONs) into biodegradable nanocapsules of poly (D,l-lactic-co-glycolic acid) (PLGA), so that these can be guided toward the brain injury by applying an external magnetic field. During the training period in the group of the Ecole de Pharmacie Genève-Lausanne (EPGL) I started the synthesis of polymeric nanocapsules with SPIONs and model proteins. This chapter describes the synthesis and characterization of the nanocapsules. CHAPTER 5 In this chapter are described the most important results obtained during the thesis. The first part regards the following results: 1. The attainment of biocompatible iron oxide nanoparticles suitable for cell therapy; 2. Non toxic labeling of endothelial progenitor cells with SPIONs. Furthermore different efficiencies in cell labeling have been reported depending on the type of EPC cell population (early - and outgrowth). It has also been shown that cell labeling efficiency may vary using different conditions of incubation time, concentration of SPIONs and particle aggregation in the culture media. Still, it has been reported no significant change in tubulogenesis (formation of inter- cellular connections) or migration ability in outgrowth EPC cell population labeled with SPIONs; 3. An increase in the release of angiogenic growth factors in outgrowth EPCs labeled with SPIONs compared to unlabeled cells; 4. A preliminary in vivo study in mice has demonstrated the migration and accumulation of endothelial progenitor cells (early populations) labeled with SPIONs in the area next to the application of the external magnetic field. In the second part of the thesis work have been achieved: 1. The synthesis of biodegradable poly (D,L-lactic - co- glycolic acid) nanocapsules by a double emulsion process, with particle sizes of 200 nm suitable for systemic administration; 2. Co- encapsulation of SPIONs and vascular endothelial growth factor (commercial protein, recombinant human VEGF165) with good efficiency. 3. Endothelial cell proliferation enhanced by the biological activity of VEGF165 encapsulated. CHAPTER 6 It contains the curriculum vitae of the author and the publications obtained during the PhD period.

This thesis investigates the synthesis and characterization of FePt nanoparticles, a material which is a promising candidate for use as an ultra-high density magnetic storage medium; relevant literature is reviewed in chapter one. Chapter two gives full details of the characterisation techniques and physical property measurements employed throughout the work described in the following chapters. This includes powder X-ray diffraction, SQUID magnetometry, transmission electron microscopy, extended X- ray fluorescence spectroscopy and Rutherford backscattering. Chapter three describes the synthesis and characterisation of FePt nanoparticles prepared by a route presented in the literature as well as one developed during this study. Chapter four describes a systematic investigation into the Rietveld refinement of powder X-ray diffraction data of iron platinum nanoparticles. From the study it is concluded which of the methodologies presented is most suitable for use in further work on iron platinum nanoparticle studies. Chapter five describes a number of in-situ variable temperature X-ray diffraction studies designed to investigate the order-disorder transition in FePt nanoparticles. A comparison between this transition in samples made via both synthetic routes discussed in chapter three is made before analysing in-depth data in order to provide information about the phase transition and its relationship with precise synthetic conditions. Chapter six describes work done on FePt nanoparticles to determine if EXAFS measurements can be obtained and modelled such that conclusions can be drawn as to the degree of order of samples prepared via different methods. Chapter seven describes a variety of magnetic studies designed to investigate the structure and properties of FePt nanoparticles. The first part of the chapter focuses on typical experiments and what use they are whilst the second part discusses the methodology and equipment required to study the phase transition of iron platinum nanoparticles, i.e. variable temperature magnetic studies.

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.

Further increase of erbium concentrations in Er-doped amplifiers and lasers is needed for the design of efficient, reliable, compact and cost-effective components for telecommunications and other photonic applications. However, this is hindered by Er concentration dependent loss mechanism known as upconversion. The upconversion arises due to non-radiative energy transfer (ET) interactions (migration and energy-transfer upconversion) among the Er ions exited to the metastable level that is used for amplification. The upconversion deteriorates the conversion efficiency of Er doped gain medium and may even totally quench the gain. The upconversion can be significantly intensified if the Er distribution in glass is non-uniform, which can be minimized by optimizing the fabrication process and the glass composition. The optimization requires detailed characterization techniques capable to distinguish between the effects caused by the uniformly distributed ions (homogeneous upconversion, HUC) and non-homogeneously distributed ions (pair induced quenching, PIQ)

The thesis deals with rigorous statistical modeling of the HUC and development of experimental methods that can provide accurate and detailed data about the upconversion, which are needed for the characterization of the upconversion.

The presented model interprets the homogenous upconversion as an interplay of ET interactions between randomly distributed Er ions, which is affected by stimulated emission/absorption of the radiation propagating in the medium. The model correspondingly uses the ET interactions parameters as the main modeling parameters.

The presented analytical model is verified by Monte-Carlo simulations. It explains strongly non-quadratic character of the upconversion observed in experiments and variety of the associated effects. The model is applicable to the interpretation of the upconversion measurements in various experimental conditions, which facilitates the upconversion characterization. The thesis also presents an advanced experimental method for accurate and detailed characterization of the upconversion in both continues-wave pumping conditions and during the decay of Er population inversion. Using the method the upconversion modeling is experimentally verified by correlating the measurements results with the modeling predictions in the whole range of the practical Er doping levels. This also allows to estimate the parameters for the ET interactions in silica. Finally, it is shown that the presented method can serve as a basis for discrimination of HUC and PIQ effects, which is crucial for optimizing the fabrication process and the glass composition.

Magnetic resonance imaging (MRI) is regularly used to obtain anatomical images, greatly advancing biomedical research and clinical health care today, but its full potential in providing functional, physiological, and molecular information is only beginning to emerge. The goal of magnetic resonance molecular imaging is to utilize MRI to acquire information on the molecular level. This dissertation is focused on ways to increase the use of MRI for molecular imaging using superparamagnetic iron oxide (SPIO) nanoparticle induced MRI contrast. This work is divided into three main sections: 1) Elucidation of the contribution of size and coating properties to magnetic nanoparticle induced proton relaxation. To maximize contrast generated without increasing particle size, new methods to increase effects on relaxivity must be developed. Experimental data obtained on a new class of biocompatible particles are presented, along with simulated data. The effects of coating size, proton exchange, and altered diffusion are examined. Simulations are presented confirming the effect of particle coatings on clustering-induced relaxivity changes, and an experimental system demonstrating the clustering effect is presented. 2) Development of a diffusion-dependent, off-resonance imaging protocol for magnetic nanoparticles. This work demonstrates an alternative approach, off-resonance saturation (ORS), for generating contrast sensitive to SPIO nanoparticles. This method leads to a calculated contrast that increases with SPIO concentration. Experimental data and a mathematical model demonstrate and characterize this diffusion-dependent, off-resonance effect. Dependence on off-resonance frequency and power are also investigated. 3) Development of a genetic MRI marker via in vivo magnetic nanoparticle synthesis. This work seeks to provide a gene expression marker for MRI based on bacterial magnetosomes, tiny magnets produced by naturally occurring magnetotactic bacteria. Here, magA is expressed in a commonly used human cell line, 293FT, resulting in the production of magnetic, iron oxide nanoparticles by these cells. MRI shows these particles can be formed in vivo utilizing endogenous iron and can be used to visualize cells positive for magA. These results demonstrate magA alone is sufficient to produce magnetic nanoparticles and that it is an appropriate candidate for an MRI reporter gene.

Iron oxide nanoparticles are of great interest as contrast agents for research and potentially clinical molecular magnetic resonance imaging (MRI). Biochemically modifying the surface coatings of the particles with proteins and polysaccharides enhances their utility by improving cell receptor specificity, increasing uptake for cell labeling and adding therapeutic molecules. Together with the high contrast they produce in MR images, these characteristics promise an expanding role for iron oxide nanoparticles and molecular MR imaging for studying, diagnosing and treating diseases at the molecular level. However, these contrast agents produce areas of signal loss with traditional MRI sequences that are not specific to the nanoparticles and cannot easily quantify the contrast agent concentration. With the expanding role of iron oxide nanoparticles in molecular imaging, new methods are needed to produce a quantitative contrast that is specific to the iron oxide nanoparticle. This dissertation presents a new method for detecting and quantifying iron oxide nanoparticles using an adiabatic preparation pulse and the failure of the adiabatic condition for spins diffusing near the particles. In the first aim, the theoretical foundation of the work is presented, and a Monte Carlo simulation supporting the proposed mechanism of the contrast is described. Adiabatic pulse prepared imaging sequences are also developed for imaging at 3 Tesla and 9.4 Tesla to highlight the translational potential of the approach for clinical examinations and scientific research, and the linear correlation of the contrast with iron concentration ideal for quantification is presented. Further, the physical characteristics of the nanoparticles and the parameters of the MRI sequence are modified to characterize the approach. In the second aim, the contrast is characterized in more realistic phantoms and in vitro, and a method to more accurately quantify nanoparticle concentration in the presence of magnetization transfer is presented. Finally, accelerated imaging methods are implemented to acquire the adiabatic contrast in a time compatible with in vivo imaging, and the technique is evaluated in an in vivo model of quantitative iron oxide nanoparticle imaging. Together, these aims present a method using an adiabatic preparation pulse to generate an MR contrast based on the microscopic magnetic field gradients surrounding the iron oxide nanoparticles that is suitable for in vivo quantitative, molecular imaging.

This thesis details three main studies. The first is an investigation of the effect of coating Fe nanoparticles in a gas to isolate the magnetic moments. An isolation or enhancement of the already increased magnetic moment of a Fe nanoparticle would have the potential for exploitation in high-moment materials. The two other investigations are of the behaviour of Fe nanoparticles in the rare earth matrices Ho and Dy. Transition metals and rare earth metals normally couple antiferromagnetically at their interface, however the intention of this work was to determine if this also happens when the Fe is incorporated as pre-formed clusters. The motivation for this is that if the interactions between the rare earth and the transition metal is switched to be ferromagnetic then the Curie temperature of the rare earth could be increased without a large decrease in its saturation magnetisation. Fe nanoparticles consisting of -200 atoms and -2nm in diameter were manufactured using a gas aggregation source then coated with H2(g). VSM, XMCD and TEM measurements were taken of these samples and the magnetic moment per atom of Fe was found to drop significantly compared to that of isolated clusters in Ag matrices. A comparative study using N2(g) was conducted yielding similar results. This is attributed to the gas permeating the whole cluster rather than forming a shell. Addition of atomic Fe to a rare earth matrix decreases the total magnetisation due to antiferromagnetic coupling. Fe nanoparticles deposited into rare earth matrices heavily quench the rare earth moment. Samples of 2-35% Fe by volume contain Fe nanoparticles large enough to disrupt the rare earth spin wave. The Fe nanoparticles couple ferrimagnetically to the rare earth producing the low overall magnetic moment. Several magnetic phase transitions were observed in all Fe/rare earth alloys. Structural measurements using EXAFS indicate that the Fe clusters may have changed to an expanded lattice within the Dy matrix.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis.
Includes bibliographical references (p. 144-157).
One of the most versatile and safe materials used in medicine are polymer-coated iron oxide nanoparticles. This dissertation describes several formulations for in vivo imaging applications. The paramagnetic polymer-coated iron oxide nanoparticle aminoSPARK is used as a fluorescence-mediated tomography (FMT) imaging agent for stratification of prostate cancer tumors. This is achieved by conjugating it to a peptide that targets SPARC (secreted protein acidic rich in cysteine), a biomarker protein associated with aggressive forms of prostate cancer. Several types of polymer coatings for iron oxide nanoparticles have been systematically explored using a novel high-throughput screening technique to optimize coating chemistries and synthetic conditions to produce nanoparticles with maximum stability and ability to lower T2 contrast for MR imaging (R2, or relaxivity). Carboxymethyl dextran emerged from the screen as an ideal coating for superparamagnetic iron oxide nanoparticles. A commercially available, FDA-approved nanoparticle with similar surface chemistry, Feraheme, was chosen as a platform nanoparticle for further development. This work presents the first instance of chemical modification of Feraheme, making it more amenable to bioconjugation by converting its free carboxyl groups to free amine groups. This amine-functionalized Feraheme nanoparticle (amino-FH) is then used as a base nanoparticle to which various targeting and reporting functionalities can be added. A FH-based nanoparticle that can be used for cell loading is synthesized by covalently combining Feraheme with protamine, a pharmaceutical that also acts as a membrane translocating agent. A rhodamine-protamine conjugate is synthesized and then covalently bound to amino-FH using carbodiimide (CDI) chemistry. This results in a magnetofluorescent cell-labeling nanoparticle (ProRho-FH) that is readily taken up by mouse mesenchymal stem cells and U87 glioma cells. ProRho-FH can be used to non-invasively track cells for development and monitoring of cell-based therapies or for further investigation of biological mechanisms such as cell migration, tumor growth, and metastasis. This combination of two FDA-approved, commercially available materials to yield a superparamagnetic and fluorescent cell labeling nanoparticle is an excellent alternative to the recently discontinued Feridex. All polymer-coated iron oxide nanoparticles used in this dissertation were thoroughly characterized to fully understand their physicochemical and magnetic properties.
by Suelin Chen.
Ph.D.

The aim of this study was to investigate how to produce iron oxide nanoparticles, with the potential for long circulation times or the ability to preferentially reach particular tissues. The preparation of iron oxide nanoparticles was achieved using inorganic solution methods to prepare particles of small size using a narrow size distribution. The nanoparticles were coated with dextran and carboxymethyl dextran as reference materials using the same method as in the preparation of the iron oxide nanoparticles. This project investigated the use of the biodegradable polymer poly(glycerol adipate) (PGA) as a coating for iron oxide nanoparticles. PGA is already used in drug delivery systems and showed an ability to control the rate of release of the drug. PGA can be readily modified with pendant functional groups leading to modifications of the physicochemical properties of the polymer. It can also be readily modified to form copolymers with the hydrophilic polymer poly(ethylene glycol) (PEG). PGA 40% acylated with stearic acid (PGA 40%C18) and the PEGylated copolymer PEG–PGA 40%C18 were synthesised for this work. The formulation of coated iron oxide nanoparticles was investigated using PGA and modified PGA polymers. The coating process was optimised producing small coated nanoparticles were measured by TEM and the best sizes are (16 ± 5 nm with PGA while with, modified PGA is 23 ±7 nm and with PEG–PGA 40%C18 is 16 ± 4 in diameter). The PGA–IONPs were over-coated by incubation with albumin and Tween. The coated particles were characterised by DLS, zeta potential, and transmission electron microscopy. The colloidal stability of the various particle formulations was investigated using increasing salt concentrations. These demonstrated that PGA–coated nanoparticles were more stable than the existing dextran formulations, and that increased stability was obtained by overcoating with albumin or Tween. A further increase in stability was seen with PEG-PGA coated nanoparticles. The cellular uptake of the RBITC labelled nanoparticle formulations was studied on the C6 medulloblastoma cell line using monolayer and 3-D aggregate cultures using fluorescence microscopy, confocal microscopy, transmission electron microscopy (TEM) and flow cytometry. The results indicated that these particles were readily internalised in C6 cells, but with an unusual subcellular distribution. Uptake was dependent on both nanoparticle concentration and incubation time. The incubation of cells with internalised particles demonstrated that particles were metabolised and fluorescence was lost from cells over a period of 4–12 hours. TEM studies showed that, after 1 hour, nanoparticles were found in all subcellular compartments, but that the route of entry into cells could not be readily determined. Experiments using 3-D cell cultures demonstrated that nanoparticles were readily taken up into aggregates, with nanoparticles penetrating deep into the aggregates. Overall, these studies demonstrated novel formulations of iron oxide nanoparticles coated with well-defined biodegradable PGA polymer layers, which were stable against aggregation under physiological conditions. These formulations show promise for use in a variety of medical applications.

Actualmente, es posible obtener nanopartículas de óxido de hierro solubles en agua y establesen entornos biológicos por medio de la descomposición térmica a altas temperaturas y el intercambiode ligandos. Este método permite un control óptimo de la distribución de tamañopara obtener nanopartículas monodispersas y con superficie apta para funcionalizar, lo cuales fundamental en aplicaciones biológicas.
Currently, it is possible to obtain iron oxide nanoparticles soluble in water with high stability in biological environments through thermal decomposition at high temperatures and ligand exchange. This method of synthesis allows good control of size distribution in order to obtain monodispersed nanoparticles with surfaces suitable for functionalization which is necessary for biological applications.

Novel iron (Fe) cross-linked alginate (FCA) beads were used for aqueous phosphate removal. Batch experiments were conducted with the beads using three different concentrations of phosphate (5, 50 and 100 mg PO43--P/L) as well as environmentally relevant (eutrophic lakes) concentration of 100 ?g PO43--P/L. About 80-97% phosphate was removed within 3 h. for lower concentrations of phosphate. The maximum phosphate sorption capacity was found to be 78.7 mg PO43--P/g of beads. Phosphate removal was not affected because of the presence of Cl-, HCO3-, SO42-, NO3- and natural organic matter (NOM). FCA beads were also used with actual lake waters (11-69 ?g PO43--P/L) and 81-100% phosphate removal was observed in 24 h. The FCA beads having a point of zero charge (PZC) of 9.2 make it an ideal candidate for phosphate removal in eutrophic lakes. Phosphate-laden spent iron cross-linked alginate (FCA) beads were used in hydroponics to evaluate the bioavailability of P and Fe using lettuce (Lactuca sativa) as a test plant. Phosphate-laden spent FCA beads were found to support the plants throughout the growth period. The bioavailability of P and Fe in the spent beads is promising considering the importance of phosphorus and iron in global nutrient security. Experiments were also conducted with lettuce and spinach (Spinacia oleracea) to evaluate the availability of iron from nanoscale zero-valent iron (NZVI). In both plants, bare NZVI enhanced the uptake of Fe as well as other essential elements. The results indicate that biofortification of spinach and lettuce with Fe is possible. The enhanced uptake of iron and other elements by lettuce and spinach is likely to have implications on global nutrient security. In another experiment, an iron-regulating gene (LsHA2) in lettuce was investigated to gain insights into the strategy taken by plants for acquisition of Fe from a readily unavailable source, e.g., NZVI. The gene of interest was found to be regulated by the presence or absence of available iron in the solution. This research is likely to give us insights into the mechanism of plant nutrient fortification with nanoparticles.
National Science Foundation (NSF)
USDA-NIFA
North Dakota Water Resources Research Institute
North Dakota Department of Commerce

Arsenic sorbs strongly to the surfaces of Fe(III) (hydr)oxides. Under aerobic conditions, oxygen acts as the terminal electron acceptor in microbial respiration and Fe(III) (hydr)oxides are highly insoluble, thus arsenic remains associated with Fe(III) (hydr)oxide phases. However, under anaerobic conditions Fe(III)-reducing microorganisms can couple the reduction of solid phase Fe(III) (hydr)oxides with the oxidation of organic carbon. When ferric iron is reduced to ferrous iron, arsenic is mobilized into groundwater. Although this process has been documented in a variety of pristine and contaminated environments, minimal information exists on the mechanisms causing this arsenic mobilization. Arsenic mobilization was studied by conducting controlled microcosm experiments containing an arsenic-bearing ferrihydrite and an Fe(III)-reducing microorganism, Geobacter metallireducens. Results show that arsenic mobility is strongly controlled by microbially-mediated disaggregation of arsenic-bearing iron nanoparticles. The most likely controlling mechanism of this disaggregation of iron oxide nanoparticles is a change in mineral phase from ferrihydrite to magnetite, a mixed Fe(III) and Fe(II) mineral, due to the microbially-mediated reduction of Fe(III). Although arsenic remained associated with the iron oxide nanoparticles and was not released as a hydrated oxyanion, the arsenic-bearing nanoparticles could be readily mobilized in aquifers. These results have significant implications for understanding arsenic behavior in aquifers with Fe(III) reducing conditions, and may aid in improving remediation of arsenic-contaminated waters.
Master of Science

Molybdenum, vanadium and iron are important micro and macro nutrients, respectively, for all living organisms. Their cycles and budgets in the natural environment is affected by - and affects many different processes. Poorly ordered ferrihydrite nanoparticles characterised for their particle size (3-5nm), crystallinity, surface area (~200m2g-1) and surface charge (point of zero charge = 7.96) helped to understand better their adsorption and co-precipitation interactions mechanisms with molybdenum and vanadium. Comparative studies of molybdenum and vanadium adsorbed onto or coprecipitated with ferrihydrite as well as the influence of different conditions such us pH, metal concentration, particles concentration and matrix composition were carried out. The obtained kinetic parameters were modelled with various geochemical software packages to evaluate their behavior. Metastability of ferrihydrite under hydrothermal conditions was the second big theme of this thesis. The crystallisation kinetic (transformation rates) and thermodynamics (activation energies) of the hematite formation were assessd with in situ synchrotronbased difraction tehnique in the presence and the absence of molybdenum and vanadium under conditions mimicing the geochemistry of deep sea hydrothermal systems (ionic strength = 0.7, pH = 8). The data showed that hematite crystallization (from ferrihydrite) followed a temperature dependent trends and that the transformation requires an apparent activation energy of 26 kJmol-1 . The presence of molybdenum and vanadium delayed the transformation reaction by 32% and 38% respectively. The transformation also leads to the sequestration of more than 90% of the initial ferrihydrite associated molybdenum and vanadium in the hematite structure, making it thus non-bioavailable for further reaction. Finally, synchrotron-based X-ray Absorption Spectroscopy revealed that the initial molybdate speciation in the starting ferrihydrite changes bonding and coordination in the end-product hematite and molybdenum replaced iron in the hematite structure further supporting the fact that molybdenum is immobilized in the hematite structure.

Nanosized magnetic structures are currently key materials for advancements in electronics, optoelectronics, magnetic storage, and many bio-inspired applications. What is usually termed ‘‘nanostructured systems’’ comprises those materials whose properties are determined by particles, crystallites, or clusters with characteristic lengths between about 1 and 100 nm. If the grain or domain size becomes comparable or smaller to the characteristic length scale of the interaction processes controlling a particular property, different effects and unusual chemical and physical properties can be expected that are highly attractive in a number of technical applications. In recent times, large advancements have been achieved related to the synthesis and characterization of well-defined, discrete magnetic nanoparticles for both fundamental and technological purposes. However, precise knowledge of the relationships between particle shape and size distribution, surface structure, and the resulting magnetic properties of magnetic nanoparticles is still lacking. In particular, iron oxide nanoparticles have been the subject of many theoretical and experimental studies. The goal of this thesis is to provide a crystallographic structural description of the atomic rearrangements in superparamagnetic maghemite (γ-Fe2O3) nanoparticles and in magneto-plasmonic nano heterostructures formed by metallic gold and magnetite (Fe3O4), looking for a relationship between the structure and the properties. The thesis is organized in 3 chapters. The first chapter is divided in two part: in the first a briefly introduction about nanomaterials is presented, in the second one all the used techniques are described. First the main concepts about powder diffraction are briefly recalled, then the Pair Distribution Function method is introduced, then there is a description of theory about Small angle X-Ray Scattering and finally ESR theory is shortly presented. In the second chapter all the beamlines of the European Synchrotron Radiation Facility, used for the data collection, are described. The heart of the thesis consists in the last chapter where all the data and the results about nanomaterials (γ-Fe2O3) and nanocomposites (Au-Fe3O4) are shown. In this chapter a thorough structural characterization was performed by using X-ray powder diffraction by means of conventional Rietveld analysis, Pair Distribution Function and Small Angle X-ray Scattering; in addition Electron Spin Resonance spectroscopy was performed on the systems to shed light on their magnetic properties.

Iron oxyhydroxides are ubiquitous in surface environments, playing a key role in many biogeochemical processes. Their characterization is made challenging by their nanophase nature. Magnetometry serves as a sensitive non-destructive characterization technique that can elucidate intrinsic physical properties, taking advantage of the superparamagnetic behaviour that nanoparticles may exhibit. In this work, synthetic analogues of common iron oxyhydroxide minerals (ferrihydrite, goethite, lepidocrocite, schwertmannite and akaganéite) are characterized using DC and AC magnetometry (cryogenic, room temperature), along with complementary analyses from Mössbauer spectroscopy (cryogenic, room temperature), powder X-ray diffraction and scanning electron microscopy. It was found that all of the iron oxyhydroxide mineral nanoparticles, including lepidocrocite, schwertmannite and akaganéite were superparamagnetic and therefore magnetically ordered at room temperature. Previous estimates of Néel temperatures for these three minerals are relatively low and are understood as misinterpreted magnetic blocking temperatures. This has important implications in environmental geoscience due to this mineral group’s potential as magnetic remanence carriers. Analysis of the data enabled the extraction of the intrinsic physical parameters of the nanoparticles, including magnetic sizes. The study also showed the possible effect on these parameters of crystal-chemical variations, due to elemental structural incorporation, providing a nanoscale mineralogical characterization of these iron oxyhydroxides. The analysis of the intrinsic parameters showed that all of the iron oxyhydroxide mineral nanoparticles considered here have a common magnetic moment formation mechanism associated with a random spatial distribution of iv uncompensated magnetic spins, and with different degrees of structural disorder and compositional stoichiometry variability, which give rise to relatively large intrinsic magnetization values. The elucidation of the magnetic nanostructure also contributes to the study of the surface region of the nanoparticles, which affects the particles’ reactivity in the environment.

La synthèse de nano-object connait un essor grandissant depuis ces 20 dernières années. Les études fondamentales de système a permis (et permet encore) de trouver de nombreux domaines d'application aux nanotechnologies, que ces soit en catalyse, en électronique, dans le domaine biomédical...La thèse se déroule autour de deux axes de recherches: la synthèse et la description des propriétés magnétique de nanoparticules de fer stabilisé par des liquides ioniques, et la synthèse, l'étude magnétique, et leur évaluation en tant qu'agent de contraste et médiateur d'hyperthermie de nanoparticules de de ferrite fonctionnalisé par des dérivées carbohydrates
The synthesis of nano-object is growing in the last 20 years. Basic research system has (and still allows) to find many areas of application for nanotechnology that is in catalysis, electronics, biomedical ...The thesis proceeds along two lines of research: the synthesis and the description of magnetic properties of iron nanoparticles stabilized by ionic liquids, and the synthesis, magnetic study, and their evaluation as a contrast agent and hyperthermia mediator of functionalized carbohydrate derivatives ferrite nanoparticles

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have unique properties with potential application in targeted cancer treatment; including the ability to generate heat when placed in an external alternating magnetic field. However, challenges such as rapid circulatory clearance by the reticuloendothelial system (RES), the need for effective functionalisation with cancer-targeting agents and heterogeneity of SPIONs, remain to be overcome. The work in this thesis aims to develop SPIONs by addressing these challenges. Ferucarbotran (Resovist®), a clinically approved MRI contrast SPION with excellent heating potential was investigated. Three main hypotheses were tested; that RES uptake of SPIONs could be blocked in vitro and in vivo, that specific targeting could be achieved by functionalising SPIONs with non-immunoglobulin cancer-targeting proteins and that product heterogeneity could be addressed by physical separation. Studies included: (i) Interactions of SPIONs with different cell types (ii) Blocking cell uptake using polysaccharide derivatives (iii) Conjugation strategies to link SPIONs to near-infrared dyes to trace their blood levels (iv) Enhancing the circulatory retention of SPIONs via RES blocking (v) Site-specific conjugation methods to functionalise SPIONs with cancer targeting protein (vi) Cellular- and immuno-assays to test the binding of functionalised SPIONs to target antigen (vii) Size exclusion chromatography (SEC) to fractionate SPIONs. Results showed that Ferucarbotran was unspecifically internalised by all tested cell lines. A range of sulfated polysaccharides were shown to block this uptake in vitro and in vivo leading to prolonged circulatory times. Ferucarbotran was successfully functionalised with cancer-targeting protein and bound specifically to target antigen in ELISA. Cellular assays with a range of cell lines revealed the generalised altered behaviour of SPIONs upon surface modification with proteins. SEC successfully fractionated Ferucarbotran into more homogeneous products with improved heating properties. In conclusion, these results are consistent with the proposed hypotheses and form a platform for addressing the challenges of SPIONs-based cancer nanomedicine.

The application of a magnetic field to a suspension of weakly magnetic nanoparticles should, based on previous work and theory, increase the aggregation between particles. This is due to the increase in the magnetic interaction in competition with repulsive forces due to the electric double layer. This hypothesis was tested using suspensions of magnetite and hematite nanoparticles. Magnetite particles were used to characterise the aggregation behaviour of strongly magnetic particles, which then served as a basis of comparison with hematite particles in a magnetic field. The expectation was that applying the magnetic field to the suspensions of weakly magnetic hematite particles would alter their aggregation behaviour to be more like that of the strongly magnetic magnetite particles. Experimental findings indicate this is not the case. No evidence was found indicating that the magnetic field altered particle interactions sufficiently to alter the aggregation. Aggregation behaviour was controlled by the chemical environment and shear forces. The magnetic field did influence the motion of the particles. In static experiments hematite particles were separated from suspension, the efficiency of which was related to the degree of aggregation and thus particle size. In stirred systems the balance between shear and Lorentz forces affected aggregate formation. As observed in previous work, small aggregation increases are possible but once aggregates reach a certain size the magnetic field affects the movement of particles and does not change interactions.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011.
Page 192 blank. Vita. Cataloged from PDF version of thesis, 2011.
Includes bibliographical references.
Iron oxides magnetic nanoparticles (MPs) of high crystallinity, high magnetization, and size-monodispersity were synthesized with oleic acid as their native ligands. These hydrophobic and non-functionalized MPs have magnetic properties that are suitable for various biological applications. Surface modifications were studied for transferring these MPs into biological environments as well as transforming them into functional nanoparticles. Certain surface modifications of MPs, such as attaching silane groups and silica coating, lead to formation of more complex structures of superparamagnetic and fluorescent silica microspheres and nanostructures. These microspheres and nanostructures comprising MPs and semiconductor quantum dots (QDs) are useful tools for biological applications such as for magnetically controlling with fluorescent tracking of particles and for bimodal imaging. Surface modifications of MPs with hydrophobically-modified polyacrylic acid (mPAA) amphiphilic polymer and catechol-derivative surfactants resulted in hydrophilic MPs that are stable in physiological environment and small in their hydrodynamic size. These MPs are also designed to possess active functional groups that are necessary for further conjugations with proteins and molecules of interest. These hydrophilic and functional MPs are useful in biological applications such as magnetic resonance imaging and sensing applications.
by Numpon Insin.
Ph.D.

Alloys used in fission and in future fusion reactors are subjected to extreme conditions including high temperatures, corrosive and intense radiation environments. Understanding the processes occurring at the microscopic level during radiation events is essential for the further development of them. As a prospective candidate material for new reactors, oxide dispersion strengthened (ODS) steels have shown good radiation resistance and the ability to trap He into fine scale bubbles, thus preventing swelling and preserving high-temperature strength. This thesis represents the findings obtained by performing computational studies of radiation effects in pure iron, Y-Ti-O systems and a simplified model of ODS using Molecular Dynamics (MD) and on-the-fly Kinetic Monte Carlo (otf-KMC) techniques. MD studies of radiation damage were carried out in a perfect body-centred cubic (bcc) iron matrix (alpha-Fe) in which yttria nanoparticles are embedded as a simplified model of an ODS steel. The results have shown how the nanoparticles interact with nearby initiated collision cascades, through cascade blocking and energy absorption. Fe defects accumulate at the interface both directly from the ballistic collisions and also by attraction of defects generated close by. The nanoparticles generally remain intact during a radiation event and release absorbed energy over times longer than the ballistic phase of the collision cascade. Also the nanoparticles have shown ability to attract He atoms as a product of fission and fusion reactions. Moreover, studies showed that He clusters containing up to 4 He atoms are very mobile and clusters containing 5 He or more become stable by pushing an Fe atom out of its lattice position. The radiation damage study in the Y-Ti-O materials showed two types of residual damage behaviour: when the damage is localized in a region, usually close to the initial primary knock-on atom (PKA) position and when PKA is directed in the channelling direction and creates less defects compared to the localised damage case, but with a wider spread. The Y2TiO5 and Y2Ti2O7 systems showed increased recombination of defects with increased temperature, suggesting that the Y-Ti-O systems could have a higher radiation resistance at higher temperatures. The otf-KMC technique was used to estimate the influence of the prefactor in the Arrhenius equation for the long time scale motion of defects in alpha-Fe. It is shown that calculated prefactors vary widely between different defect types and it is thus important to determine these accurately when implementing KMC simulations. The technique was also used to study the recombination and clustering processes of post-cascade defects that occur on the longer time scales.

Doctor of Philosophy
Department of Chemistry
Stefan H. Bossmann
Recent development of a variety of superparamagnetic and ferromagnetic iron/iron oxide (Fe/Fe₃O₄) nanoparticles with different surface chemistry have been widely studied for numerous biological applications such as drug delivery, as diagnostics, hyperthermia and magnetic resonance imaging. The wide applications of Fe/Fe₃O₄ nanoparticles are possible since they exhibit favorable properties as high magnetization ability, are smaller than 100 nm in size, they can be coated with several ligands which allow drug delivery at a specific site and are biocompatible. By using Fe/Fe₃O₄ nanoparticles as drug delivery agents treatment costs and side effects can be reduced, however treatment efficacy can be increased. We have demonstrated that Fe/Fe₃O₄ nanoparticles can be utilized in different methods depending on their properties, to be used as therapeutic agents for cancer treatment. In one method we have taken advantage of the Fe/Fe₃O₄ nanoparticles magnetic ability to produce hyperthermia (heat) in cancer cells when subjected to an alternative magnetic field. Here we use the cell based delivery system since the size of the nanoparticles are small they can be taken up by monocyte/ macrophage like cells for systemic transportation to the inflamed cancer cite. The hyperthermia study was conducted in mice with pancreatic cancer. This study demonstrated that the life expectancy of the mice increased by 31%. In the next method we took the advantage of the surface chemistry of the Fe/Fe₃O₄ nanoparticles and changed it with dopamine-peptide and dopamine-thiosemicarbazone ligands. The advantage of the peptide is to deliver the nanoparticle to its target site and the thiosemicarbazone analogue is used as an iron chelator that would initiate apoptosis in cancer cells. This nanoplatform was tested in 4T1 breast cancer cell line and normal fibroblast cell line and demonstrated that it was effective towards the cancer cell line than the normal cell line at a ratio of 5:1 of thiosemicarbazone analogue : dopamine on the nanoparticle. However further studies are needed to be done to clarify the effectiveness of this nanosystem.

Nanoparticles have come and continue to be an extremely interesting research topic due to the variety of applications, deriving from the possibility to opportunely tailor their properties through different preparation methods. Among nanoparticles, magnetic nanostructures, due to their special characteristics, represent an interesting tool for advanced applications. Focusing our research on the synthesis and characterization of magnetic nanoparticles, we developed materials for potential advanced applications. In the framework of my PhD research, I devoted myself on two main potential applications: in the biomedical field for magnetic drug delivery and in the environmental field for heavy metals capture and organic pollutant degradation. The research has been always performed on magnetic nanosized structures, dealing with iron-based particles since they allow to obtain, in an easy and reliable way, a product with specific and welldefined properties. The PhD research activity was mainly focused on the synthesis and characterization of magnetic nanoparticles, opportunely functionalized and engineered to be applied in biomedical and environmental fields. The difference of the two applications required opportunely tailored materials, and thus proper synthetic methods have been adopted. The work will be divided into two main parts separated for the specific application where synthetic protocols, characterizations and results are reported and extensively discussed. In both applications, ferrite nanoparticles were opportunely synthesized and functionalized. Within the biomedical field, the main effort was done to synthetize the optimal nanoparticles based material to be conjugated with a fluorescent tripeptide and to evaluate the drug release activated through an enzyme recognition and cleavage process. Instead within environmental field, opportune functionalized nanoparticles were employed in toxic metals capture and recovery from waters, performing static and dynamic procedures. Experiments among photocatalysis were also performed; magnetite or ferrite nanoparticles were used as nucleation seeds in the synthesis of TiO2 nanoparticles achieving excellent efficiency in degradation of Methylene Blue.

[Truncated abstract] In the past decade, the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) has received considerable attention due to their potential applications in biomedical fields. However, success in size and shape control of the SPIONs has been mostly achieved through organic routes using large quantities of toxic or/and expensive precursors in organic reaction medium at high reaction temperature. This has limited the biomedical applications of SPIONs and therefore, development of a synthetic method under aqueous condition that is reproducible, scalable, environmentally benign, and economically feasible for industrial production is of paramount importance in order to fully realise their practical applications. Spinning Disc Processing (SDP) has been used to synthesise superparamagnetic magnetite (Fe3O4) nanoparticles at room temperature via a modified chemical precipitation method under continuous flow condition and offer a potential alternative to be applied to SPIONs production. SDP has extremely rapid mixing under plug flow conditions, effective heat and mass transfer, allowing high throughput with low wastage solvent efficiency. The synthesis process involves passing ammonia gas over a thin aqueous film of Fe2+/3+ which is introduced through a jet feed close to the centre of a rapidly rotating disc (500-2500 rpm). Synthetic parameters such as precursor concentrations, temperature, flow rate, disc speed, and surface texture influence the particle sizes. ... Magnetic silica microspheres are receiving great attention for possible applications in magnetic targeting drug delivery, bioseparation and enzyme isolation. However, the current available methods for preparation suffer from the setback of low loading of Fe3O4 nanoparticles in the silica microsphere, which result in low magnetic moment, thereby limiting their practical applications. Therefore it is of considerable importance to develop new alternative synthetic methods for fabricating magnetic silica microspheres with high magnetic nanoparticles loading. Superparamagentic Fe3O4 nanoparticles (8-10 nm diameter) and curcumin have been encapsulated in mesoporous silica in a simple multiplestep self assembly approach process with high Fe3O4 nanoparticles loading (37%). The synthesis involves loading of curcumin in the Cetyltrimethylammonium bromide (CTAB) micellar rod in the presence of superparamagnetic Fe3O4 nanoparticles via a parallel synergistic approach. The synthesised magnetic mesoporous silica composite material is stable, superparamagnetic with high saturation magnetisation before and after curcumin leaching experiment. Under physiological pH in phosphate buffer, the curcumin is slowly released over several days. These magnetic mesoporous silica are expected to have great potential as targeted drug delivery systems.

This thesis focuses on the synthesis and applications of nanoscale zero valent iron (nZVI) in the environmental remediation of contaminants. The polyvalent characteristics of this nanomaterial are evaluated in this work with the study of its application in a wide range of contaminants: heavy metals and pesticides in water medium, and malodorous sulfur compounds present in air streams. Moreover, a novel method of synthesis of encapsulated nZVI from a waste material is presented, which meets the principles of green chemistry and at the same time represents a low-cost method of obtaining nZVI with improved characteristics. Chapter 1 describes the current state of the topics that will be discussed in the rest of the thesis. Specifically, the different mechanisms of contaminant remediation by nZVI are discussed, a summary of the current synthesis methods is presented and the principal modifications of nZVI to improve its characteristics are described. Finally, the limitations of the current techniques are assessed, which will be the starting point of the thesis. In Chapter 2, the application of nZVI to heavy metal removal during long time periods is explored. The contaminants studied are Zn, Cd, Ni, Cu and Cr, which are the most common heavy metals found in ground and wastewater. A delivery-effect of the heavy metal ions that had already been attached to nZVI surface is observed after long reaction times, which is a consequence of the nZVI aging and oxidation. The conditions that influence the delivery-effect are assessed and possible solutions to this detected problem are presented. In Chapter 3, nZVI is applied to the removal of sulfur-based odorous compounds in air streams. The compounds studied are hydrogen sulfide and dimethyl disulfide (DMDS), which are commonly found in wastewater treatment plants. Both nZVI loading and pH are varied to assess their influence on the process. Bimetallic nanoscale particles of Cu/Fe, Ni/Fe and Pd/Fe are synthesized in order to improve the DMDS abatement by the nZVI. The advantages of this new method for odor removal are discussed at the look of the experimental results. Lastly, a pilot scale test was performed in a wastewater treatment plant in order to test the effectiveness of the nZVI in a real application. The nZVI were applied in a scrubber to eliminate the sulfurous compounds from the pre-treatment area of the wastewater treatment plant. Chapter 4 deals with the application of nZVI to the oxidation of non-biodegradable pollutants by the Fenton reaction. Specifically, the effect of pH on the degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is studied. The advantages of using nZVI as a Fenton reagent compared to homogeneous Fenton are described. Furthermore, the addition of UV-light to the process is investigated. Finally, the main degradation intermediates of the reaction are identified and a degradation mechanism is accordingly proposed. In Chapter 5, the presence of polychlorinated dioxins and furans (PCDD/Fs) in the nZVI surface is addressed. Studies have shown that nZVI enhances the formation of such chlorinated compounds during thermal processes, but it is unclear which the origin of the compounds is. It has been suggested that nZVI could possess impurities such as PCDD/Fs in its surface. Therefore, the concentration of PCDD/Fs in both commercial and laboratory-synthesized nanoparticles is analyzed. PCDD/Fs pattern and WHO-TEQ concentrations are also obtained. As an outcome of the results obtained in this chapter, a recommendation for preventing the PCDD/Fs presence in nZVI is given. Chapter 6 is dedicated to the synthesis of carbon-encapsulated nanoparticles using hydrothermal carbonization (HTC) of an agricultural waste, particularly, olive mill wastewater (OMW). This novel method, in addition to meet the green chemistry principles, makes profit of the high polyphenol content of OMW to maximize the fraction of incorporated iron into the nZVI. Moreover, the carbon layer surrounding the nZVI protects it against oxidation and avoids its aggregation. Several HTC conditions are explored to study their implications in the characteristics of the material obtained. A deep characterization of the encapsulated nZVI is also presented in this chapter. In Chapter 7, the applications of the encapsulated nZVI synthesized in Chapter 6 are explored and compared for the same contaminants that have been studied in the previous chapters. Then, the advantages of encapsulated nZVI in comparison with common nZVI are discussed at the end of the chapter, and an estimation of the synthesis costs with this method is addressed. Lastly, in Chapter 8, the main conclusions of the thesis are summarized and suggestions for future work are presented.

Thesis (Ph. D.) -- University of Maryland, College Park, 2005.
Thesis research directed by: Chemical Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

One of the most challenging goals in nanoparticle research is to develop successful protocols for the large-scale, simple and possibly low-cost preparation of morphologically pure nanoparticles with enhanced properties. The work presented in this thesis was focused on the synthesis, characterisation and testing of magnetic nanoparticles and their potential applications. There are a number of magnetic nano-materials prepared for specific applications such as metal oxide nanoparticles encapsulated with various porous materials including Fe₃O₄/Fe₂O₃ coated with soft bio-organic materials such as glycol chitosan and bovine serum albumin and hard materials such as silica (SiO₂) and zinc sulphide (ZnS). The preparation of these materials was achieved principally by bottom-up methods with different approaches including micro-emulsion, precipitation, electrostatic and thermolysis processes. The thesis also presents the uses of various analytical techniques for characterising different types of nano-materials including Attenuated Total Reflection Fourier Transformer Infrared Vibrational Spectroscopy (ATR-FTIR), Ultraviolet Visible- Near Infrared (UV-Vis-NIR) Spectroscopy, Zeta Potentiometric Surface Charge Analysis, Superconducting Quantum Interference Device (SQUID) and Vibration Sample Magnetometry (VSM) for magnetic analysis and powder X-Ray Diffraction (XRD) for crystallographic pattern analysis. There are many applications of magnetic nanoparticles, including nano-carriers for biological and catalytic reagents. The magnetic nanoparticles can facilitate separation in order to isolate the carriers from solution mixtures as compared to many inefficient and expensive classic methods, which include dialysis membrane, electrophoresis, ultracentrifugation, precipitation and column separation methods. There are six key chapters in this thesis: the first chapter introduces the up-to-date literature regarding magnetic nano-materials. The uses of magnetic nano-materials in drug binding and for protein separation are discussed in the second and third chapters. The fourth chapter presents the use of magnetic nanoparticle in conjunction with a photo-catalytic porous overlayer for the photo-catalytic reduction of organic molecules. The fifth chapter describes different analytical techniques used for the characterisation of nanoparticles and the underlying principles and the experimental details are also given. The sixth chapter summarises the results and provides an overview of the work in a wider context of future applications of magnetic nanoparticles.

Engineered nanoparticles are defined as having a dimension that is between one and one hundred nanometres. With toxicology studies reporting various degrees of toxicity the need to investigate nanoparticle fate and behaviour is vital. Monodispersed engineered nanoparticles were synthesised in-house to produce suitable materials to examine such processes. Iron oxide nanoparticles (5 nm) and citrate coated silver nanoparticles (20 nm) were subjected to different conditions of pH, ionic strength and different types of commercially available natural organic matter. Changes in particle size and aggregation were examined using a multi-method approach. Results showed that the natural organic matter was able to absorb onto nanoparticle surfaces and improve their stability when subjected to changes in pH and ionic strength, where they would normally aggregate. The presence of higher concentrations of NOM in some cases promoted aggregation due to bridging. This work also concluded that silver nanoparticles could be produced in the presence of NOM without additional stabilisers and that they themselves were stable. This work has demonstrated that engineered nanoparticles could remain stable within a range of environmental conditions, and thus raise future pollution concerns.

We aim at better understanding how nucleation occurs in a gas condensation chamber, discussing in particular the formation of iron nanoparticles in Argon atmosphere and Helium atmosphere, and the use of the method of moments to study their growth.

Magnetic nanoparticles are of great interest for a wide range of applications. This work has focused on three primary forms of iron based nanoparticles and combinations thereof: α-iron, iron oxide, and iron carbide or cementite. The synthesis of several core-shell particles including cementite-iron oxide, α-iron-cementite, and α-iron-iron oxide was accomplished through reverse micelle routes and high temperature decomposition of iron pentacarbonyl in various media. Structural analysis to confirm the structures was performed using extended x-ray absorption fine structure (EXAFS) techniques. A rapid characterization technique was developed utilizing a correlation between Fourier transform infrared spectroscopy and EXAFS to determine the full metal cation distribution between the octahedral and tetrahedral sites in manganese zinc ferrite (MZFO). This method was then used to show that the initial Fe3+ to Fe2+ ratio in MZFO synthesis could be used to design a desired cation distribution and affected the zinc incorporation levels into the resultant ferrite. Functionalization of nanoparticles for aqueous dispersions and ferrofluids has varying degrees of importance, depending on the application. In applications such as magnetic resonance imaging (MRI) where the targets are biological systems, it was important to produce solutions that will not aggregate in the high magnetic field of the MRI. It was also vital to characterize decomposition mechanisms and products that would be presented to the body after use as a contrast agent. This work has provided insight into both the preparation of magnetic samples for MRI applications and implications of the biocompatibility of reactive and decomposition products. Three successful methods of forming dispersions that would not aggregate in the high magnetic field of the MRI were comprised of cysteine/polyethylene glycol (PEG), PEG based ferrofluids, and dopamine/PEG. The dopamine functionalization however showed reactivity with the iron/iron oxide nanoparticles and led to the formation of the cytotoxic dopamine quinone and resulted in the destruction of the nanoparticles. Using all three types of dispersions to compare the iron based nanomaterials, the MRI measurements concluded with the iron oxide ferrofluid yielding the highest R2 enhancement.

Cette thèse présente le développement de nanoparticules hybrides avec un coeur inorganique et une couronne organique pour des applications médicales. Des nanoparticules d’oxyde de fer ont été obtenues par synthèse polyol, en contrôlant leurs cristallinités, leurs morphologies (monocoeur ou multicoeur) et leurs tailles (de 4 à 37 nm). Leurs propriétés ont été évaluées et comparées pour de possibles applications théranostiques : en thérapie pour le traitement du cancer par hyperthermie magnétique, pour le diagnostic en tant qu’agents de contraste pour l’IRM. Les surfaces des nanoparticules ont été modifiées par greffage de polymères/polypeptides pour apporter de la stabilité en milieux biologiques et de nouvelles fonctionnalités. Le poly(éthylène glycol) (PEG) a été greffé pour ses propriétés de furtivité, le poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) et des polypeptides dérivés de l’élastine (ELPs) pour leurs propriétés thermosensibles, et la sonde fluorescente DY700 pour permettre le suivi des nanoparticules in vitro et in vivo. Les propriétés magnétiques et thermosensibles de ces nanoparticules coeur-couronne ont été étudiées avec un instrument unique combinant l’hyperthermie magnétique et un système de diffusion dynamique de la lumière. Ainsi, les variations de température, de diamètre et d’intensité diffusée ont pu être mesurées simultanément. Les propriétés de nanoparticules monocoeur et multicoeur greffées avec du PEG, et des nanoparticules monocoeur greffées avec un ELP contenant un peptide pénétrant ont d’abord été évaluées in vitro. Leurs internalisations dans des cellules de tumeur cérébrale humaine (glioblastome) ont permis d’étudier leurs cytotoxicités après traitement par hyperthermie magnétique, et ont montré une baisse de viabilité cellulaire jusqu’à 90 %. In vivo, l’injection intraveineuse de ces nanoparticules dans des souris a abouti à une accumulation dans les tumeurs. L’injection intratumorale suivie du traitement par hyperthermie magnétique a conduit à des élévations de température locales d’environ 10 °C, avec un effet significatif sur l’activité des tumeurs
This thesis reports the development of hybrid nanoparticles made of an inorganic iron oxide core and an organic shell for medical applications. Iron oxide nanoparticles (IONPs) were produced by the polyol pathway, leading to a good control over their crystallinity and morphology (monocore or multicore). IONPs with diameters in the range of 4 to 37 nm were produced. Their properties as MRI contrast agents were assessed and compared, for possible theranostic applications. They can be used for treating cancer by magnetic hyperthermia, and as contrast agents for MR imaging. The surface of the IONPs was modified to bring stability in biological conditions, as well as new functionalities. Poly(ethylene glycol) was grafted for its stealth property, poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) and elastin-like polypeptides (ELPs) for their thermosensitive capabilities, and a DY700 fluorescent probe was grafted for tracking nanoparticles in vitro and in vivo. The magnetic and thermosensitive properties of the nanoparticles were studied using a unique set-up combining magnetic hyperthermia with dynamic-light scattering. This set-up allowed measuring the elevations of temperature of the samples as well as variations in diameter and backscattered intensity. Monocore and multicore IONPs grafted with PEG, and monore IONPs grafted with a diblock ELP were tested in vitro. Their interactions with glioblastoma cells were studied, from the internalization pathway inside the cells to their cytotoxic effect (up to 90 %) under magnetic hyperthermia. In vivo, nanoparticles intravenously injected in mice accumulated in the tumors. Intratumoral administration followed by magnetic hyperthermia treatment led to elevations of temperature of up to 10 °C, with a significant effect on the tumor activity

Thesis Submitted in Fulfilment of the Requirements for the Degree Master of Technology: Chemical Engineering in the Faculty of Engineering at the Cape Peninsula University of Technology 2014
Iron oxide nanoparticles have recently become attractive for use in gas sensing, as catalysts and have also shown promise in other fields, such as biomedicine, for targeted drug delivery and cancer treatment. Despite these growing applications, the ability to produce iron oxide and one dimensional (1D) iron oxide nanoparticles on an industrial scale has proven to be a challenge. The continuous hydrothermal synthesis, (CHS), method has been proposed as the most promising method, yet the effect of the operating parameters on particle characteristics are still widely contested in the literature. One such parameter, temperature, is still widely contested on its effect on APS. To address this issue, a CHS pilot plant was constructed and commissioned. The inability to isolate certain parameters in CHS is a common shortcoming. Parameters such as temperature and flow rate are prime examples, as changing the temperature has several effects on the system resulting in a change in reaction rate, a change in density and a change in the reactor residence time while the flow rate is closely linked to the residence time and mixing conditions. A 3-level Box-Behnken factorial design method was used to statistically analyze the correlations and interactions between operating parameters (temperature, concentration and flow rate) in CHS and evaluate their resulting effect on particle characteristics, with focus on morphology. All particles were characterized by X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM). Reactions in the presence of solvents or surfactants proved incapable of modifying particle morphology, although significant particle size reduction revealed that they were actively involved in particle growth and may be used as a further tool for controlling particle characteristics. The concentration was found to have the greatest effect on particle characteristics including a slight alteration of particle shape and a massive influence on the average particle size. The interactions between operating parameters were significant, especially in the case of temperature and concentration. The temperature and concentration were found to interact revealing three different trends on APS, offering a solution to conflicting reports in the literature. The temperature was also observed to interact favourably with the flow rate, presenting a method of increasing the PY and RC, with little change in APS and PSD. This knowledge will prove invaluable for the design of future experiments in CHS.

Au-coated magnetic Fe nanoparticles have been successfully synthesized by partial replacement reaction in a polar aprotic solvent with about 11 nm core of Fe and about 2.5 nm shell of Au. In this work, a combination of TEM (transmission electron microscopy), XRD (X-ray Powder Diffractometry), EDS (Energy disperse X-ray spectroscopy), SQUID (Superconducting Quantum Interference Device), TGA (Thermograviometric analysis), UV-visible absorption spectroscopy and Faraday rotation were employed to characterize the morphology, structure, composition and magnetic properties of the products. HRTEM images show clear core-shell structure with different crystal lattices from Fe and Au. SQUID magnetometry reveals that particle magnetic properties are not significantly affected by the overlayer of a moderately thick Au shell. The Au-coated particles exhibit a surface plasmon resonance peak that red-shifts from 520 to 680 nm. And all the above characterizations show that in this sample, there are no Fe oxides inside the particle.

Target specific delivery of anticancer drugs to the effected site without showing systematic toxicity to normal tissues is important. Multifunctional biodegradable delivery systems reduce systematic toxicity in an efficient manner. These drug carriers should provide controlled release, be directed towards desired site, track payloads via contrast imaging, heat the effected sites and trigger drug release. In this context, superparamagnetic iron oxide nanoparticles based drug delivery systems are highly desirable. Superparamagnetic iron oxide nanoparticles upon exposure of alternate magnetic field could be directed and provide heat to localised areas. Moreover, superparamagnetic iron oxide nanoparticles also have image contrast ability for magnetic resonance imaging. This study aimed to develop biocompatible superparamagnetic iron oxide nanoparticles. These nanoparticles were coated by bioinspired materials such as peptides (diphenylalanine) to achieve monodispersed dual efficient such as drug carriers and hyperthermia. Thermally responsive core-shell materials with tubular and spherical morphologies without compromising the inner cores properties such as superparamagnetism is highly desirable. Two shapes of iron oxide (spherical and tubular) were prepared using co-precipitation of iron (II) and (III) ion and oxidative hydrolysis of ferrous sulphate in alkaline solutions, respectively. Spherical peptide shells were synthesised using tert-Butyloxycarbonyl modified diphenylalanine peptide in ethanol-water (1:1) mixture. Tubular peptide shells were prepared using similar diphenylalanine non-modified peptide. The iron oxide nanoparticles (spherical and tubular) were encapsulated via template-mediated synthesis using ultra-sonication and vortex-mixing methods. These materials were characterised using variety of techniques such as, zetasizer, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDAX), Fourier Transform Infrared Spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) analysis, Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Vibrating Sample Magnetometer (VSM) and magnetic field induced hyperthermia. The diameter of spherical superparamagnetic iron oxide nanoparticles were measured to be ranges from 10 to 35 nm and rod-shaped core materials showed nearly 10 nm width and several hundred nanometres in length. Spherical peptide were approximately 1 µm in diameter. Tubular-shaped peptide were between 100-300 nm in width and several micrometres in length. These peptides were used as shells for the preparation of core-shell composites. Both spherical and rod-shaped core-shell composites were similar in dimensions to the pure peptide particles. Observational analysis confirmed the presence core-shell composition. Spherical iron oxide core materials were crystalline magnetite (Fe3O4) structures confirmed by powder XRD. These magnetite nanocrystals were further modified with a biocompatible silica shell. Brunauer–Emmett–Teller (BET) analysis revealed a mesoporous shell structure. Spherical peptide shells were found to be amorphous and tubular peptide shells were crystalline in nature. VSM of core-shell composite materials depicted superparamagnetic nature, hence these materials have ability to heat over the exposure of applied external magnetic field for hyperthermia ablation. Anticancer drug (doxorubicin, DOX) loading and release profile of bare spherical and rod-shaped iron oxide nanoparticle and peptide, silica and peptide-capped silica coated spheres were studied for potential therapeutic application. The doxorubicin loading efficiency was observed to be ranging from 12 % to 90 % depending on the type materials. The in vitro drug release profiles were measured at 37 °C without the exposure of magnetic field in incubation and with applied magnetic field. Time-dependent studies showed sustained release of DOX in silica coated and peptide- capped silica coated spherical superparamagnetic iron oxide nanoparticles were ranging from 0 to 30 % over 72 hours of incubation. Concentration dependent studies revealed that the ratio of 1:100 (doxorubicin:superparamagnetic iron oxide nanoparticles) had the maximum loading efficiency with minimum release capability. Exposure to Alternate Current (AC) magnetic field (200 G; 406 kHz) the spherical materials generated hyperthermia in a time dependent manner reaching 50 °C in 3 minutes. Tubular peptide coated iron oxide materials did not induce heat even after 25 minutes of exposure indicating weak superparamagnetism. Magnetic field triggered drug release was seen only in spherical core-shell nanocomposites with 6X higher compared at 37 °C without exposure.

Multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) coated with silica are a promising research field for lots of biomedical applications. The scope of this work is a preparation of SPIONs and coating them with silica to form core-shell structured nanoparticles for nanomedicine applications. SPIONs were synthesized by two chemical methods – co-precipitation and thermal decomposition of organic iron precursor. Prepared nanoparticles were carefully characterized –average size, size distribution, morphology, crystallinity, colloidal stability and magnetic properties were studied. After comparing SPIONs synthetized by two routes the most suitable method for biomedical applicable nanoparticles preparation is determined. The nanomedicine requires nanoparticles of the highest quality. The next step was coating SPIONs with silica shell. For this purpose inverse microemulsion method was chosen. TEOS was used as a silica precursor. Mean size, size distribution, magnetic properties, structure of silica shell were studied.

AbstractThe overall objective of this research is to evaluate significant mechanisms for deposition of surface-modified NZVI in granular subsurface media during transport. Although surface-modified NZVI have been shown to transport more easily than bare NZVI, there is a lack of knowledge of how different parameters such NZVI particle concentration, NZVI size, aqueous-phase flow velocity, and sand particle size influence nanoparticle transport. To investigate the effects of these parameters on transport, a number of laboratory experiments were conducted with NZVI synthesized from ferrous sulfate in the presence of polymers that were effective in colloidal stabilization of the particles. The bare and surface modified-NZVI was characterized for size and surface chemistry by a wide array of analytical instruments. The polymer-stabilized NZVI were employed in three different studies to identify parameters that influence deposition of NZVI in model, granular, subsurface media. In the first study, the breakthrough patterns of carboxymethyl cellulose (CMC)- and polyacrylic acid (PAA)- stabilized NZVI eluted from packed sand columns under a range of pore water velocities and NZVI influent concentrations were investigated. The NZVI effluent relative concentrations of both types of particles decreased with decreasing flow velocities and increasing particle concentrations. PAA-NZVI exhibited slower elution from the columns than CMC-NZVI under identical experimental conditions, and this is attributed to more rapid aggregation kinetics of PAA-NZVI. The second study focused on the quantitative evaluation of aggregation kinetics and the possible effects of aggregation on NZVI deposition. Aggregation of CMC-NZVI particles resulted in a change in particle size distribution (PSD) with time, and the changes in particle size were evaluated by nanoparticle tracking analyzer (NTA). The effects of particle concentrations on the transport in porous media were evaluated by comparing the time profiles of elution of CMC-NZVI from packed sand columns. Changes in PSD over time were responsible for a gradual increase in effluent concentration between 1 and 4 pore volumes, and beyond 4 pore volumes particle detachment contributed to non-steady state effluent concentrations. The NZVI elution profiles had a good fit with aggregation kinetics equations coupled to colloid transport equations that account for particle deposition and detachment. The third study focused on assessing the significance of straining of CMC-NZVI particles during transport in model subsurface porous media. Laboratory experiment were conducted to assess the transport of CMC-NZVI in columns packed with four different sized sands and with three different concentrations. . Breakthrough curves (BTC) and retention profiles of CMC-NZVI along the column length were analyzed to characterize CMC-NZVI transport. The breakthrough curves suggest that with decrease in mean sand diameter, the effluent concentrations decrease. Very high CMC-NZVI particle retention towards the inlet, particularly for the finer sands was observed. These observations are consistent with particle retention in porous media due to straining and/or wedging. Two colloid transport models considering 1) particle deposition by attachment only, and 2) particle retention by straining along with particle deposition by attachment were fitted to the experimental data. Comparison of experimental data and the model calculations suggest that in addition to deposition on collector surface, CMC-NZVI particles are removed from the solution by straining in packed sand beds, with straining rate coefficients that decrease with increase in sand diameter.
L'objectif global de cette recherche est d'évaluer les mécanismes importants de déposition des particules NZVI modifiées en surface dans les milieux granulaires subsurfaciques pendant le transport. Bien que les particules NZVI modifiées en surface aient montré un transport plus facile que les particules NZVI nues, il y a un manque de connaissance sur la façon dont des simples paramètres, tel que la concentration des particules NZVI, leur taille, la vitesse d'écoulement de la phase aqueuse et la taille des particules de sable, influencent le transport des nanoparticules. Dans la première étude, on a étudié les modèles des particules CMC- et PAA-ZVI élues des colonnes remplies de sable dans une gamme de vitesses de l'eau des pores, et des concentrations influentes de particules NZVI. . Les concentrations effluentes relatives des deux types de particules NZVI ont diminué avec la diminution des vitesses d'écoulement et avec l'augmentation des concentrations des particules. Les particules PAA-NZVI présentaient une élution plus lente que les particules CMC-NZVI dans des conditions expérimentales identiques, ceci étant attribué à une cinétique d'agrégation plus rapide pour les particules PAA-NZVI. La réduction de la stabilité colloïdale due à l'agrégation des particules CMC- et PAA-NZVI a été vérifiée en utilisant les tests de sédimentation et on a trouvé que les particules PAA-NZVI ont été moins stables que les particules CMC-NZVI. La deuxième étude portait sur l'évaluation quantitative de la cinétique d'agrégation et les effets d'agrégation possibles sur la déposition des particules NZVI. L'agrégation des particules CMC-NZVI a entraîné un changement dans la distribution de la taille des particules (PSD) avec le temps, et les changements dans la taille des particules étaient évalués par l'analyse de suivi des nanoparticules (NTA). Les effets de la concentration des particules dans la gamme sur le transport dans les milieux poreux ont été évalués en comparant les profils de temps d'élution des particules CMC-NZVI dans les colonnes remplies de sable. Les profils d'élution des particules NZVI ont eu un bon ajustement avec les équations cinétiques d'agrégation couplées aux équations de transport colloïdal, qui tiennent compte de la déposition des particules et de détachement. La troisième étude portait sur l'évaluation de l'importance de la filtration des particules CMC-NZVI pendant le transport dans les milieux poreux subsurfaciques modèles. Des expériences de laboratoire ont été effectuées pour évaluer le transport des particules CMC-NZVI dans les colonnes et trois concentrations différentes. Les courbes percées (BTC) et les profils de rétention des particules CMC-NZVI le long de la colonne ont été analysés afin de caractériser le transport. Les courbes BTC suggèrent que les concentrations effluentes diminuent avec la diminution du diamètre moyen du sable. Une très élevée rétention des particules CMC-NZVI a été observée, particulièrement pour les sables plus fins. Ces observations sont en accord avec la rétention des particules dans les milieux poreux due à la filtration et au calage. Deux modèles de transport colloïdal qui considèrent 1) la déposition des particules uniquement par attachement, et 2) la rétention des particules par filtration et déposition par attachement, ont été ajustés aux données expérimentales. La comparaison des données expérimentales avec les calculs du modèle suggèrent qu'en plus de la déposition sur la surface du collecteur, les particules CMC-NZVI sont retirées de la solution par filtration dans les lits remplis de sable, avec des coefficients de filtration qui diminuent avec le diamètre du sable.

>Magister Scientiae - MSc
During the course of this study iron oxide nanoparticles, which have been researched for drug-targeted delivery, were synthesised via the co-precipitation method and characterised using various methods. This study focused on the role of relevant capping agents for the inhibition of agglomeration of the particles; chitosan, polyvinyl alcohol (PVA) and poly lactic glycolic acid (PLGA) were the capping agents of interest. The study is an assessment of the effects brought about the different capping agents used for this work. The prepared particles were then capped with the different capping agents followed by the loading of the drug curcumin. Various analytical methods were used to analyse the particles such as High resolution transmission electron microscopy (HR-TEM), Superconducting quantum interference device (SQUID), Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA) and zeta potential. PVA, chitosan and PLGA capped SPIONS were successfully prepared and verified by FT-IR spectrometry, various sizes were prepared almost ranging the same for the successfully prepared particles verified by XRD. The resultant particles were found to be spherical with an average particles size between 13- 22 nm. From the study it was concluded that the addition of the different capping agents resulted in the reduction of the intensity of the peaks in XRD, it was also found out the presence of the capping agents did not alter the crystalline phase of the particles. From the study it was also observed that higher saturation magnetization was experienced where PVA was used as the capping agents.

Current methods of cancer therapy and detection still warrant high demand and great developments. Utilising the fundamental magnetism of iron oxide nanoparticles, it is possible to harness that magnetic power for the development of new, influential therapeutic and imaging modalities. In this thesis, a detailed look into the use of iron oxide nanoparticles as a material for magnetic thermotherapy and bio-imaging will be undertaken. Iron oxide nanoparticles are synthesised using a common co-precipitation synthesis. Stabilisation was achieved with citrate molecules followed by advanced functionalisation of the nanomaterial with gold achieved via reduction of Au3+ (HAuCl4) to Au0 from the citrate ligands. These materials were shown to exhibit remarkable intrinsic heating power when under the influence of an external alternating current magnetic field. Following the potential of iron oxide nanoparticles functionalised with gold for magnetic hyperthermia, multimodal imaging and therapeutic probes were studied. Iron oxide gold nano were analysed as possible Raman enhancer substrates. Finally, iron oxide nanoparticles were synthesised using an organic photoacoustic dye as a stabilising ligand to functionalise the magnetic Fe3O4 cores with optical properties. This lead to the novel co-precipitation synthesis of indocyanine green (ICG) and Flamma®774 covalently attached to Fe3O4 nanoparticles.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2014.
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references (pages 130-136).
Uniformly sized superparamagnetic iron oxide nanoparticles (SPIONs) with inorganic diameters of 3-35 nm were synthesized. New surface ligand coatings were designed and synthesized, and the resulting hydrophilic SPIONs in biological buffers were found to be compact, stable, highly magnetic, and biocompatible. Furthermore, the hydrophilic SPIONs were stable in vitro in serums and cells as well as in vivo in mice. Functionalized SPIONs demonstrated the ability of specific labeling. Finally, the hydrophilic SPIONs have potential as a non-toxic alternative to Gadolinium based contrast agents for T₁-weighted magnetic resonance imaging (MRI) and they have shown potential in multicolor MRI as well as magnetic particle imaging.
by He Wei.
Ph. D.

Doutoramento em Física
Este trabalho aborda algumas propriedades magnéticas e estruturais de nanopartículas de óxidos e óxidos-hidróxidos de ferro crescidos em matrizes híbridas orgânicas-inorgânicas. As matrizes híbridas, denominadas di-ureasils e obtidas pelo processo sol-gel, são compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils não dopados está modelada como grupos de domínios siliciosos com dimensões nanométricas, estruturalmente correlacionados no seio de uma matriz rica em polímero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de óxidos e óxidos-hidróxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanopartículas de ferrihidrite dá-se em condições ácidas à superfície dos domínios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleação. Desse modo dá-se uma nucleação heterogénea, onde o tamanho das nanopartículas depende da concentração de ferro (entre 1 e 6% em massa), sendo a concentração de partículas constante. As propriedades magnéticas das nanopartículas de ferrihidrite revelam a existência de interacções antiferromagnéticas e de momentos descompensados. A contribuição destas duas componentes nas curvas de magnetização em função do campo magnético pode ser separada usando um método aqui proposto, o que permite um adequado estudo da evolução do momento magnético com a temperatura. O estudo das propriedades magnéticas dinâmicas das partículas de ferrihidrite, através de susceptibilidade ac, medidas de relaxação e medidas de efeito Mossbauer, permitiu estudar a evolução das interacções dipolares em função da concentração de ferro, bem como determinar a distribuição de barreiras de energia de anisotropia no caso em que essas interacções são desprezáveis. É apresentado um novo método para comparação desta distribuição com a distribuição de tamanhos, que permitiu concluir que os momentos magnéticos descompensados estão aleatoriamente distribuídos em volume. Usando baixas concentrações de água, foi possível crescer fases de oxihidroxinitrato de ferro com diferentes graus de cristalinidade, sendo algumas precursoras da ferrihidrite (como observado noutros trabalhos) e sendo outras novas fases. O crescimento de nanopartículas de maguemite e magnetite acontece após incorporação de iões de Fe2+ e Fe3+ seguidos de tratamento básico e térmico. Estes sistemas apresentam propriedades magnéticas típicas de nanopartículas superparamagnéticas sem interacções dipolares. As propriedades magnéticas dependem criticamente da existência de grupos isocianato livres, que actuarão como pontos de nucleação.
The present work focus on the structure and the magnetic properties of iron oxide and iron oxide hydroxide nanoparticles grown in organic-inorganic hybrids. The sol-gel derived matrix, termed di-ureasils, is a siliceous network to which oligopolyoxyethilene chains with different molecular weight are grafted by means of urea cross-links. The di-ureasils local structure was modelled as groups of nanometric siloxane correlated domains embedded in a polymericrich media. In this thesis, the controlled growth of ferrihydrite, iron(III) oxyhydroxynitrate phases, maghemite and magnetite in di-ureasils is demonstrated. Ferrihydrite nanoparticles are formed at low pH on the siliceous surface, where the carbonyl groups act as nucleation points. This implies an heterogeneous nucleation, where the nanoparticles size depend on the amount of iron (in the 1 to 6% wt range) and the nanoparticles concentration is constant. The ferrihydrite nanoparticles have antiferromagnetic and uncompensated/canted moments, responsible for linear and saturation components in the dependence of the magnetization with field, respectively. These components can be separated by a new method here presented and an accurate dependence of the magnetic moment with temperature determined. The dynamic magnetic properties of ferrihydrite were studied by ac susceptibility, relaxation and Mossbauer measurements. These studies allowed the determination of the evolution of the dipolar interactions with the iron content and the determination of the anisotropy energy barrier distribution in cases where such interactions are negligible. Comparing the energy barrier distribution with the size distribution allowed to conclude that the uncompensated moments are randomly distributed in volume. This conclusion is based on a new method here presented, that uses distributions to investigate the power law relation between physical quantities. Antiferromagnetic iron(III) oxyhydroxynitrate phases with different degrees of crystallinity are formed when using low water concentrations in the sol-gel process. Some of these are precursors of ferrihydrite, as previously found in literature, but others constitute new phases. Maghemite and magnetite nanoparticles can be grown inside diureasils after the incorporation of Fe2+ and Fe3+ ions, followed by basic and thermal treatment. The magnetic properties show the existence of noninteracting superparamagnetic nanoparticles. Evidence for the possibility of tuning the magnetic properties of the system by allowing the existence of free isocyanate groups acting as nucleation sites was found.