Дисертації: "Iron oxide superparamagnetic nanoparticles"

1

Sreeja, V. "Synthesis and studies on superparamagnetic iron oxide nanoparticles." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2011. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/3773.

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2

Abdollah, M. R. A. "Developing superparamagnetic iron oxide nanoparticles as targeted cancer nanomedicine." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1473874/.

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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.

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3

Masoodzadehgan, Nazanin Hoshyar. "Superparamagnetic iron oxide nanoparticles development, characterization, cupper-64 labeling and cellular tracking." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/43619.

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Development of nanostructures as MR contrast agent will significantly improve the field of disease diagnostics. Contrast agents such as iron oxide nanoparticles are less toxic compared to more commonly used gadolinium based agents. A subclass of iron based nano particles are super paramagnetic iron oxide nano particles, (SPIOs) which are widely studied MR contrast agents useful in both imaging and drug delivery applications. In this work, SPIOs were synthesized and characterized and used for cellular tracking and multi modal labeling. A new solvent exchange method was utilized to coat different core size iron oxide nano particles. SPIOs were characterized for in-vivo imaging using MR and they had a very uniform size distribution which was determine using dynamic light scattering (DLS) and transmission electron microscopy. Furthermore, blood circulation half-life of 16nm SPIOs were determined through tail vein injection. SPIOs have many applications among which is the in vivo tracking of stem cells which is critical for determination of stem cells fate after injection. Magnetic Resonance (MR) as a non-invasive method can provide significant information about the fate of the cells as well as determination of the success rate of therapeutic cellular deliveries. Mesenchymal stem cells can be loaded with super paramagnetic iron oxide nano particles (SPIOs) and have their movements followed once planted in vivo. We present our findings on the effect of SPIO concentration and stem cell density on the MR signal and transverse relaxation time. Our preliminary results indicated that SPIOs do not cause mesenchymal stem cell cytotoxicity and do not affect proliferation ability up to 200 μg/ml concentration. The release of the nanoparticles was investigated 24 hours post internalization and the result showed that SPIOs will stay inside the cell. We also found that the contrast increases in a concentration dependent manner. Our results suggest that using MR with low concentration of SPIOs is a novel and promising method for tracking of mesenchymal stem cells. In this work SPIOs were also labeled with 64Cu to investigate their potential for multi modal positron emission tomography (PET) MR imaging. Dual modality PET MR SPIO contrast agent can be synthesized to image diseases such as cancer and atherosclerosis. The advantage is the non-invasive and early detection of disease at molecular lever before it has spread to late stages or in case of the atherosclerosis before the plaque has blocked the vessel. To develop a multi modal contrast agent, a positron emitter, 64Cu (half-life of 12.701 ± 0.002 hours), was used in labeling and synthesis was performed all in one step with the addition of 64Cu chelator, 14-PE DTPA followed by radiolabeling for both 6.5nm SPIO and 17nm SPIO. After labeling and purification with the desalting column, the amount of dissociated 64Cu in the solution was determined using radio thin layer chromotagraphy (TLC) and the particle was shown to have minimum amount of fee 64Cu. Serum stability of labeled SPIO was determined in vitro by incubating 64Cu-labeled SPIOs in mouse serum at 37 °C for 24 hr with constant shaking. Radio TLC result then revealed that 64Cu stays bounded to the SPIO after 24 hours in mouse serum. This means that 64Cu labeled SPIO has a great potential as a dual modality contrast agents and further in-vivo studies are required to verify the findings.

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4

Majid, Abdul. "Thermally responsive peptide coated superparamagnetic iron oxide nanoparticles for drug delivery." Thesis, University of Central Lancashire, 2017. http://clok.uclan.ac.uk/20743/.

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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.

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5

Marinin, Aleksandr. "Synthesis and characterization of superparamagnetic iron oxide nanoparticles coated with silica." Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-121520.

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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.

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6

Carrara, C. "SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES (SPIONS): DESIGN AND SYNTHESIS OF NEW NANOCONJUGATES." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/214973.

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Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have demonstrated great promise for diagnostic and therapeutic applications. Thanks to their magnetic properties and to their size, comparable to that of biologically objects, they are very useful for biomedical applications, such as, for example, automated DNA extraction, targeted gene delivery, magnetic resonance imaging (MRI), and magnetic field induced hyperthermia for cancer therapy.For these applications, SPIONs must be coupled with targeting agents, therapeutic drugs, and other functional probes. Hence, the need to develop efficient synthetic strategies for the conjugation of molecules to SPIONs is an important and appealing target. The strategies used can involve passive noncovalent adsorption on the outer particle surface or the formation of a more stable covalent bond by using appropriate heterobifunctional linkers, in which one functional group specifically binds the nanoparticle, while the other reacts with the biomolecule in order to form the new nanoconjugate. In this thesis, the use of an heterobifunctional linkers containing an isocyanate moiety as new functional group able to directly bind SPIONs will be shown. We were able to demonstrate that the NCO moiety is able to directly reacts with the surface hydroxyl groups exposed on the outer nanoparticles surface leading to a covalent carbamate-like bond. Comparison with classical non-covalent and covalent anchoring methodologies were also performed. To further confirm the possible application of this new anchoring methodology, new SPION-PNA (Peptide Nucleic Acid, mimics of natural oligonucleotides) nanoconjugates were synthesized and their binding affinity towards complementary DNAs were evalueted.

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7

Chin, Suk Fun. "Superparamagnetic nanoparticles for biomedical applications." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2009. http://theses.library.uwa.edu.au/adt-WU2009.0128.

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[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.

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8

Sotto, David C. "Directing the migration of mesenchymal stem cells with superparamagnetic iron oxide nanoparticles." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54897.

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Cell migration plays an important role in numerous normal and pathological processes. The physical mechanisms of adhesion, protrusion/extension, contractions, and polarization can regulate cell migration speed, persistence time, and downstream effects in paracrine and endocrine signaling. Methods for understanding these biophysical and biochemical responses to date have been limited to the use of external forces acting on mechanotransductive receptors. Additionally, as the use of magnetic nanoparticles for cell tracking and cell manipulation studies continues to gain popularity, so does the importance of understanding the cellular response to mechanical forces caused by these magnetic systems. This thesis work utilizes superparamagnetic iron oxide nanoparticles and static magnets to induce an endogenous magnetic force on the cell membrane. This cell manipulation model is used to better understand the mechanobiological responses of mesenchymal stem cell to SPIO labeling and endogenous force generation. Directionally persistent motility, cytoskeletal reorganization, and altered pro-migratory cytokine secretion is reported in this thesis as a response to SPIO based cell manipulation.

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9

Angelopoulos, I. "Magnetic actuation of smooth muscle cells loaded with superparamagnetic iron oxide nanoparticles." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1461225/.

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Faecal incontinence (FI) is a debilitating disorder that affects a significant portion of the population. The research included in this thesis aimed to test the hypothesis that magnetic actuating of smooth muscle cells loaded with superparamagnetic iron oxide nanoparticles (SPION) can modify the cell phenotype, which could be used with as a future therapy. The research focused on exploring a novel method of magnetic actuation and assessing its effects on the phenotype and biocompatibility of human rectal smooth muscle cells (HRSMC). A 2D model was used to demonstrate the effects of SPION on HRSMC. Initially, the effect of incubating HRSMC with different concentrations of SPION (0, 31.25, 250 and 1000 μg/ml) for 24 hours was investigated. Transmission electron microscopy revealed that SPION were endocytosed by cells and became concentrated inside endosomes. Superconducting quantum interference device (SQUID) measurements showed that SPION loading was concentration dependent and also that saturation occurred for concentrations above 250 μg/ml. SPION loading of HRSMC led to inhibition of the gene expression of actin and calponin when incubated in differentiation medium, with or without magnetic actuation, suggesting SPION caused the cells to shift towards a more proliferative phenotype. Live cell imaging revealed actuation of SPION-loaded HRSMC with stronger magnets led to an observable movement of internalized SPION and the plasma membrane. The findings from this research indicate SPION is biocompatible and may alter the phenotype of HRSMC. Therefore, SPION may offer novel benefits for regenerating damaged muscle in the treatment of FI. Further investigation is needed to assess the effects of magnetic actuation on SPION loaded cells.

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10

Peacock, A. K. "Surface modified superparamagnetic iron oxide nanoparticles for long term stem cell tracking." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3000750/.

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In the initial stages of this project, the aim was to develop polymer coated superparamagnetic iron oxide nanoparticles (SPIONs) which would be stable in physiological buffer solutions at 37 °C (body temperature) for cell labelling experiments. Well-defined end functional hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) homopolymers were prepared by atom transfer radical polymerisation (ATRP) and used to couple onto the surface of functionalised SPIONs using an end grafting-to approach. pMPC was chosen due to its well-known biocompatibility. The pMPC coated SPIONs were investigated as a potential T2 magnetic resonance image (MRI) contrast agent through biocompatibility and colloidal stability screening prior to biological studies of the polymer coated SPIONs with stem cells. In the later stages of this project, silica and gold nanoparticle (NP) surface coatings were individually investigated for their chemical stability and protection of the SPION core to acidic conditions mimicking those found in the lysosome of the stem cell. This was carried out in order to develop and screen a coating that would enable long term stem cell tracking. Again, the nanomaterials prepared were assessed for biocompatibility and their magnetic properties were measured prior to stem cell labelling studies. In the final chapter, the nanomaterials prepared throughout this Thesis were subjected to stem cell labelling and the retention of the nanomaterials inside stem cells was investigated.

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11

Roberts, Geraint Rhys Dafydd. "Superparamagnetic iron oxide nanoparticles : foundations for novel bioconjugate species and multimodal contrast agents." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/110803/.

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The properties of superparamagnetic iron oxide nanoparticles (SPION) have led to them being a major area of research within the ‘nano-revolution’. A number of SPION species have been used in disease imaging, including multimodal contrast agents active in positron emission tomography (PET) and magnetic resonance imaging (MRI), as well as bioconjugate species where biomolecules have been immobilised on the nanoparticle’s surface. The western world faces an epidemic of conditions for which monoclonal antibodies (mAbs)have become seen as a ‘magic bullet’. However, the expense of mAb therapy, possible side effects and the desire to maximise treatment success require improvements in patient stratification and selection. Chapter 1 introduces the field of biomedical imaging and immunotherapy and describes how research into immunoPET and PET/MRI imaging overlap in the following chapters. Chapter 2 describes the development of reliable, reproducible methods of synthesising SPION and introducing a number of biocompatible coatings with useful functionalities. These techniques underlie the chemistry to be discussed in Chapter 3- the immobilisation of biomolecules on the surface of SPION. Typical linker chemistry is discussed, with the relative merits of different approaches expanded upon. The effect of initial reaction stoichiometry on enzymatic activity is explored as a model for later experiment design. Chapter 4 incorporates several of the aspects examined in earlier chapters to describe the synthesis of radiolabelled SPION bioconjugated to the clinically approved antibody trastuzumab to give a novel immunoPET contrast agent. Fluorescence activated cell sorting (FACS) analysis and fluorescence microscopy confirm the in vitro validation of these agents. In vivo experiments show how these agents require further development before reaching a human clinical context. Chapter 5 relates the effort to synthesise novel coordination systems based on the hypoxiaselective imaging agent 64Cu-ATSM. The co-ordination chemistry of these systems with several metals is described.

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12

Neubert, Jenni [Verfasser]. "Effects of Clinically Relevant Superparamagnetic Iron Oxide Nanoparticles on Murine Primary Brain Cells / Jenni Neubert." Berlin : Freie Universität Berlin, 2018. http://d-nb.info/1176634178/34.

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13

Lakay, Eugene Marlin. "Superparamagnetic iron-oxide based nanoparticles for the separation and recovery of precious metals from solution." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/1866.

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14

Wu, Xian. "Magnetophoretic Capture of 5 nm sized Superparamagnetic Iron Oxide Nanoparticles Under Different Gradient Field Conditions." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587651389722581.

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15

Alali, Muqdam. "Amino acid-modified ultrafine superparamagnetic iron oxide nanoparticles : fabrication, size characterisation and potential cytotoxicity and cell interaction." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/52434/.

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The potential applications of transition metals-based nanoparticles are expanding in the biomedical field. Oxides of iron are the matter of investigation in this study where various preparations of ultrafine superparamagnetic iron oxide nanoparticles (USPIONs) were fabricated using flow injection technology with spinning disc reactor. Basically, two types of preparation parameters were examined; first, instrument-related (physical) parameters and, second, chemistry-related parameters. USPIONs fabricated by this instrument showed fine-tuning size adjustment. Subsequent surface modification of these nanoparticles produced hydrophobic, hydrophilic and neutral amino acids modified surface, whereby aminoacid ‘monomers’, rather than polymeric materials were used. Transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements, thermogravimetric analysis (TGA) and fourier-transform infrared-attenuated total reflection spectroscopy (FTIR-ATR) were employed to characterise the coated nanoparticles. The data show that ultrafine, 4-9 nm sized coated nanoparticles show good dispersion upon TEM imaging. Measurement of number of monomers molecules effectively associated with USPIONs suggest formation of multilayer of amino acid adsorbed on nanoparticles (NPs). Prediction of NPs- amino acid association mechanism by FTIR-ATR study reveals presence of either monodentate or bidentate molecular adsorption on the surface of USPIONs. In the second stage of the project, interactions of differently modified USPIONs with epithelial cell layer (model of intestinal epithelium) are now investigated. An intestinal adenocarcinoma cell line (Caco-2) is used for performing the in vitro studies. The toxicity of three types of USPIONs (Asp-, His-, and Phe-USPIONs) reveals that these particles have potential toxic effect on biological system. Relatively long term exposure to these particles (24 hours) with high concentration 250 μg/ml and more was found to enhance apoptotic mode of cell death. Cell-NPs interaction study displayed presence of different forms of cellular interaction which are supposed to be related to USPIONs surface chemistry. While some of Phe-USPIONs are found internalised and accumulated inside some cells, Asp-USPIONs exhibit different interaction mode where the cell membrane of most cells is covered with thin layer of NPs without significant cell penetration. This gives an indication that metal oxide NPs (USPIONs) that are associated by their surface with small molecules could render these NPs with aggravated toxicity and cell-NPs interaction and hence long term effect.

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16

Sadat, Md Ehsan. "Probing the Magnetic Relaxation Dynamics and Optical Properties of Superparamagnetic Iron-Oxide (Fe3O4) Nanoparticles for Biomedical Applications." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447689870.

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17

Al-Saadi, Ali. "Preparation and characterisation of encapsulation magnetic metal iron oxide nanoparticles." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:57bdcf38-9d45-48ab-a971-a2d60e2e4391.

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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.

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18

Pang, Rosita. "Mechanisms of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs)-mediated Cytotoxicity in Human Neural Precursor Cells and Glioblastoma Multiforme." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25842.

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One of the novel treatments of cancer is to use USPIONs to create reactive oxidative stress on the cancer cells. However, there was no research of this nanoparticle on Glioblastoma Multiforme (GBM), which is the most common and lethal brain tumour. The key feature of these nanoparticles is their high stability and relaxivity, so that we can visualize the distribution of nanoparticles in high contrast using magnetic resonance imaging (MRI) (Eamegdool et al., 2014). Thus, we can track the distribution of the anti-neoplastic drugs tagged USPIONs in the GBM of the brain. This could also be applicable for tracking human neural precursor cells (hNPCs) for stem cell therapy. Therefore, my PhD study has focused on how USPIONs will affect the biological functions of hNPCs and GBM cells in vitro. To assess this, we have measured the cell viability, heat shock protein (HSP) protective mechanism, cytotoxicity, migration, proliferation, mitochondrial potentials, and various biological functions of hNPCs and GBM cells exposed to USPIONs. This project has also provided insights into the mechanism of entry and the cellular interaction of USPIONs on hNPCs and GBM cells. With the ubiquitous presence of nanoparticles (NPs) in the environment and the extensive application of iron oxide nanoparticles in industry and medical applications, hNPCs were utilized to represent a normal, healthy neuronal cell model to examine potential cytotoxicity induced by USPIONs. While the cytotoxic effect of USPIONs on GBM cells could provide valuable insights into cancer treatments by targeting the heat shock protein (HSP) protective pathways. In Chapter 2, we have observed that USPIONs entered the hNPCs through clathrin-mediated endocytosis using transmission electron microscopy (TEM) and dynasore which is an inhibitor of clathrin-dependent endocytosis. This data has shown that USPIONs localized within vesicles of the cytoplasm, and some USPIONs were proximal to the mitochondria. It was also found that continuous exposure to a high dosage (20 μg/mL) of USPIONs could induce a Fenton-like reaction, which potentially induced reactive oxygen species (ROS) and protein misfolding. Following, mitochondrial dysfunctions including mitochondrial membrane depolarization, mitochondrial permeability transition pore (mPTP) opening, cytochrome c (Cyt c) release and calcium dysfunction were detected. Although HSP protective mechanism was shown to be involved to compact the toxicity of USPIONs, this protective mechanism was overwhelmed at a later stage of exposure as evident by the increase in nitric oxide (NO) and disruption of the bioenergetic profile from 16 hr. Following, Caspase 3/7 activation and a reduction in cell viability were detected at 24 hr. Taken together, these findings have provided valuable insights to assess possible cytotoxicity and safe dosage of USPIONs before the application of tracking hNPCs using MRI. In Chapter 3, we have shown the potential cytotoxicity of USPIONs on CNS-1 cells, a rat GBM model with infiltrative and growth patterns similar to human gliomas. This study has demonstrated that exposure to 20 μg/mL USPIONs could induce oxidative stress in CNS-1 cells, activating the HSP protective response mechanism, which was later overwhelmed, causing a reduction in cell viability at 12 hr. In due course, HSPs were then upregulated, re-activating the HSP protective mechanisms and eventually cell viability similar to control was detected. Therefore, by targeting this HSP protective mechanism in CNS-1 cells and the cytotoxicity induced by high dosage of USPIONs exposure, this could provide insights into novel cancer therapeutics for GBM. In Chapter 4, we have investigated the cellular interaction of the co-administration of 20 μg/mL USPIONs, HSP inhibitors, deferoxamine (DFO), ironomycin (AM5) and Bafilomycin A1 in B30, primary GBM cells. The results have shown that the co-administration of Bafilomycin, HSP70 inhibitor and USPIONs could cause lysosomal dysfunction. In addition, HSP90 inhibitor along with USPIONs, DFO, AM5 and Bafilomycin induce the greatest reduction in autophagy. Taken together, the findings from this chapter have contributed to new understandings of the usage of USPIONs, HSP inhibitors, DFO, AM5 and Bafilomycin for magnetic hyperthermia therapy, autophagic pathways-targeted toxicity and other therapeutic interventions for GBM treatments. This thesis has compared the cytotoxic effects of high dosage (20 μg/mL) exposure of USPIONs to hNPCs, CNS-1 cells and primary B30 cells. In addition, the results have shown that the amount of USPIONs uptake is the least in hNPCs, followed by CNS-1 cells and then primary B30 cells. While cytotoxicity affecting the mitochondrial functions are seen across all three models, HSP protective mechanisms were involved in protecting the cells from further cellular insults induced by USPIONs. Thus, targeting the HSP protective mechanisms along with the multiple cellular stress and cytotoxicity induced by USPIONs could provide insights into novel anti-cancer therapy.

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19

Khalid, Muhammad Kamran [Verfasser]. "Processing and characterization of tailor-made superparamagnetic iron oxide nanoparticles (SPIO-NPs) for pharmaceutical applications / Muhammad Kamran Khalid." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2019. http://d-nb.info/1219965340/34.

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20

Patel, Ronakkumar S. "Development, Characterization, and Magnetic Hypothermia Behaviors of Engineered Fe3O4 Nanocomposites for Biomedical Applications." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1368024719.

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21

Morillo, Martín Diego. "Superparamagnetic iron oxide nanoparticles as arsenic adsorbent. Development of Nanofiber SPION Supports and Arsenic Speciation Using Synchrotron and Hyphenated Techniques." Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/129335.

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Los estudios que se han realizado en la presente tesis doctoral se basan en el desarrollo de una metodología de síntesis y caracterización de sistemas nanoestructurados como recurso innovador para la recuperación de arsénico en efluentes contaminados y la depuración de dichos efluentes. Estos materiales tienen como elemento común, el uso de las Superparamagnetic Iron Oxide Nanoparticles (SPION), con las que se han realizado diferentes estudios de adsorción para evaluar los parámetros de adsorción óptimos (tiempo de contacto, efecto del pH y de la concentración). Dichos estudios han permitido determinar la máxima capacidad de adsorción del SPION a la hora de extraer el elemento contaminante y observar como se ve afectada dicha capacidad de adsorción, en función de la especie existente del elemento contaminante. La elección de SPION se fundamenta en el empleo de la fuerte interacción Fe-As demostrada en muchos compuestos naturales, así como por su capacidad magnética. A partir de éste estudio, se han desarrollado diferentes sistemas adsorbentes en modo no soportados, basados en la funcionalización del SPION (NanoComposites) o bien empleando sistemas soportados, ya sean con esponja de celulosa (Forager® Sponge) impregnada de SPION o los más novedosos, sistemas basados en nanofibras (de acetato de celulosa y poliacrilonitrilo). En este último caso, dichos sistemas son sintetizados vía electrospinning y cargados con SPION con el objetivo de incrementar la superficie específica de adsorción y facilitar su posible aplicación en muestras reales. Todos los sistemas desarrollados disponen de un valor añadido, ya que las propiedades magnéticas del SPION permiten recuperar las nanopartículas que pueden quedar expuestas en las disoluciones contaminadas de una manera rápida y efectiva, evitando así, una contaminación con nanopartículas del efluente tratado. El trabajo realizado, ha permitido optimizar tanto la síntesis de SPION, vía co-precipitación, como el desarrollo y caracterización de los sistemas adsorbentes. Adicionalmente, tras determinar la máxima capacidad de adsorción para cada uno de los sistemas, se ha estudiado la selectividad de dichos sistemas por las especies de arsénico en presencia de iones metálicos (Cu2+, Ni2+ o Zn2+) y/o de los aniones más comunes en aguas (cloruro, nitrato, sulfato y fosfato). En lo referente a los estudios de especiación, se han aplicado técnicas de especiación directa (técnicas de radiación sincrotrón) e indirecta (acoplamiento HPLC-ICP-MS) para determinar la selectividad de los materiales frente a las diferentes especies inorgánicas de arsénico (arsenito o arsenato), obteniéndose resultados satisfactorios que denotan una elevada selectividad por As(V). Por otra parte, se han evaluado las características y propiedades de los diferentes sistemas adsorbentes. Dicha actividad ha comportado el empleo de diversas técnicas analíticas, desde la microscopia (SEM y TEM) que permiten conocer el tamaño, distribución y morfología de las nanopartículas y nanofibras, hasta técnicas que proporcionan información sobre las características estructurales y propiedades físico-químicas de los materiales. Así pues, los estudios llevados a cabo para la realización de esta tesis doctoral proporcionan un significativo avance en el desarrollo de una serie de potenciales sistemas adsorbentes, los cuales pueden ser aplicados para la eliminación de contaminantes altamente tóxicos como el arsénico en muestras reales. Dicha aplicación, se caracteriza por unos valores de eficiencia, eficacia y selectividad comparables, cuando no superiores a materiales existentes en el mercado. Un ejemplo de la transferencia tecnológica derivada de esta tesis doctoral, es la patente solicitada “Filtro de tratamiento de líquidos con nanopartículas de magnetita y procedimientos correspondientes”. Ref: P201330144 y con fecha de prioridad del 6 de Febrero de 2013.
The studies that have been carried out in the present PhD thesis Project are based in the development of a synthesis methodology and characterization of nanostructured systems as an innovative facility for the recovery of arsenic from contaminated effluents and the purification of these effluents. These adsorbent materials have a base element, Superparamagnetic Iron Oxide Nanoparticles (SPION). With this nanoparticles have carried out arsenic adsorption experiments to evaluate the optimum adsorption parameters (contact time, pH effect and concentration effect). These studies have made it possible to determine the maximum adsorption capacity of SPION when the contaminant element is extracted, observe how is affected this adsorption capacity depending of the contaminant element existing specie. It is expected to use the high affinity and string interaction between Fe-As as it is proved in several natural compounds. Then, taking into account the previous work with SPION, different adsorbent systems have been developed, non-supported nanostructured systems by SPION surface functionalization (NanoComposites) or supported nanostructured systems as SPION loaded over a cellulose sponge (Forager® Sponge) and the most innovative, SPION loaded electrospun nanofibrous systems (with polymers such as cellulose acetate and polyacrylonitrile). In this last case, these systems have been synthesized by electrospinning techniques with the main aim of increase the specific surface area and to make easier the real sample applications. These nanostructured systems have an added value because of the SPION magnetic properties let recover the nanoparticles that are exposed in the contaminates solutions in a quick and effective way, avoiding then, an unwanted contamination with nanoparticles of the treated effluent. The developed work have made possible the SPION Synthesis by co-precipitation method was optimized and the development and characterization of the nanostructured adsorbent systems were performed successfully. Thus, apart from the maximum adsorption capacity determination for each system, arsenic selectivity of this systems was performed in presence of metal ions (Cu2+, Ni2+ o Zn2+) and/or in presence of most common interfering anions in water (chloride, nitrate, sulphate and phosphate). Regarding the speciation studies, direct (Synchrotron radiation techniques) and indirect (Hyphenated HPLC-ICP-MS) speciation techniques were put in practice to determine the selectivity of each system for the different inorganic arsenic species, arsenite or arsenate, obtaining successfully results of the arsenate selectivity for all systems. Furthermore, the characteristics and the properties of the adsorbent systems have been evaluated. Several techniques have been used, from microscopic techniques (SEM y TEM) that let measure and understand the size, distribution and morphology of nanoparticles and nanofibers, to other techniques as X-ray diffraction (XRD) or magnetization measures (SQUID) that provide information about structural characteristics and physico-chemical properties. All in all, this work provides knowledge, demonstrated advances and different nanostructured adsorbent systems that can be potentially applied to remove highly toxic contaminants such as arsenic. An example of the appropriate technologic transference derived from the PhD. Thesis is the Spanish Patent “Filtro de tratamiento de líquidos con nanopartículas de magnetita y procedimientos correspondientes”. Ref: P201330144 with priority date on Febrery 6th, 2013.

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Walkup, Laura L. "Fundamental studies and applications for the development of novel MRI contrast agents: Hyperpolarized xenon-129 and superparamagnetic iron oxide nanoparticles." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/dissertations/859.

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Since its discovery in the mid-1950s, the phenomenon of nuclear magnetic resonance (NMR) has been recognized as a powerful, nondestructive analytical technique capable of probing the structure and dynamics of many systems-- ranging in size from simple organic molecules, through large biomolecular complexes, and even the tissues of the human body by use of magnetic resonance imaging (MRI). Indeed, MRI is perhaps the most well-known application of MR, and in the clinic, MRI is growing in popularity as an alternative to other imaging modalities such as computerized tomography (CT), positron emission tomography (PET), and x-ray, all of which rely on ionizing forms of radiation to generate images. Both NMR and MRI operate on the same physical principles as discussed in Chapter 1: the manipulation of populations of nuclear spins in different energy states using radiofrequency (rf) pulses. This dissertation work focuses on the development of two different types of MRI contrast agents: hyperpolarized 129Xe gas and superparamagnetic iron oxide nanoparticles (SPIONs). The largest `Achilles' Heel' of MR techniques is their inherent lack of detection sensitivity due to the exceedingly small magnitude of the nuclear spins, giving rise to small thermal polarizations. Chapter 2 reviews strategies for improving the MR spin polarization, and the following chapter focuses on the physics of one such strategy-- spin-exchange optical pumping (SEOP), which is used to prepare highly spin-polarized noble gases (e.g., 3He and 129Xe). SEOP is a two-step process whereby first, the electronic spins of an alkali metal vapor become polarized via the absorption of circularly-polarized resonant laser light, and second, the electronic spin polarization is transferred from the alkali metal atoms to the nuclear spins of the noble gas atoms via collisions; Chapter 4 discussed the experimental considerations and implementation of SEOP. Hyperpolarized noble gases prepared via SEOP have a wide variety of MR applications, reviewed in Chapter 5, including use in pulmonary MRI where the hyperpolarized noble gas provides contrast in the lung-space. The development of hyperpolarized 129Xe as contrast for pulmonary MRI has suffered on two fronts: firstly, due to the physics of SEOP, generating large volumes of highly spin-polarized gas is challenging, and secondly, the commercial devices used to perform SEOP and prepare the hyperpolarized gas, so-called `hyperpolarizers', are expensive and proprietary, which has limited access to the technology to researchers and clinics. Chapter 7 discusses the design and construction of a fully automated, clinical-scale, `open-source' 129Xe hyperpolarizer with the purpose of developing an accessible, lower cost, mostly `off-the-shelf' alternative to commercial polarizers. The hyperpolarizer operates at high Xe densities and provides high polarizations (i.e., ~90%, ~57%, ~50%, and ~30% at Xe partial pressures of ~300, ~500, ~760, and ~1570 torr, respectively) and currently is housed at Brigham and Women's Hospital where it has received full FDA/IRB approval and is involved in in vivo pulmonary imaging studies. Preliminary developments and results from a second-generation 129Xe hyperpolarizer are discussed in Chapter 8 which includes improvements in the optical design, gas handling manifold, and SEOP oven. The `open-source' hyperpolarizer design allow for greater access to hyperpolarized gas technology, and in time, as more laboratories adopt the design and expand upon it, a community of scientists and clinicians using hyperpolarized gas will grow and facilitate the sharing of ideas. The final SEOP-related chapter discusses fundamental studies of N2 temperatures during SEOP conducted in situ with Raman spectroscopy which shed light on the thermalization of energy during SEOP and the interrelation between key experimental SEOP parameters. The second aspect of MRI contrast discussed is the use of SPIONs as environmentally- sensitive contrast agents, and the synthesis and applications of SPIONs are reviewed in Chapter 6. Among other features, SPIONs offer high biological tolerability and flexible surface chemistry to allow for functionalization which can be exploited to yield differential MR response in different chemical environments. One general biological parameter of interest is tissue pH where local reductions in pH are associated with a variety of conditions including inflammation and cancers, and Chapter 10 focuses on the development of melamine dendron-functionalized SPIONs as pH-sensitive MRI contrast agents. Also discussed is a model for understanding how SPION clustering affects MR response. Such contrast agents could be developed as molecular imaging agents capable of mapping tumor pH in vivo.

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23

Trojahn, Ulrike. "Characterization of novel anti-EGFR single domain antibodies and their application in active targeting of superparamagnetic iron oxide nanoparticles to glioblastoma." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107747.

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Glioblastoma multiforme is the most lethal primary brain tumor with a mean patient survival of 12 - 15 months. Efforts to treat glioblastoma with chemotherapeutics or radiation therapy have been largely ineffective, which is why the current treatment paradigm is predominantly based on surgery. Herein, it has been shown that the extent of surgical resection is correlated with patient outcome, i.e. less residual cancer cells result in a prolonged time to recurrence. In glioblastoma patients, magnetic resonance imaging (MRI) is used in diagnosis, MRI-guided surgery, and monitoring of disease progression. Superparamagnetic iron oxide nanoparticles (IONPs) are currently receiving increased attention as MRI contrast agents for brain imaging. Their reported proton relaxation properties, biocompatibility, and retention times are superior to the commonly employed gadolinium-based contrast agents. In addition, their larger surface area allows for the conjugation of targeting moieties and/or labels used for multi-modal imaging (e.g. fluorophores, radioisotopes). One of the most frequent genetic alterations in primary glioblastoma involves the epidermal growth factor receptor (EGFR). EGFR over-expression due to gene amplification is observed in 50 - 71% of the patients and among these the simultaneous expression of EGFR mutants is frequently seen. The most common mutation is the deletion of exon 2 – 7 of the extracellular domain, which results in ligand-independent, constitutive activation of the intracellular kinase domain. This mutant is named EGFRvIII and has been intensely investigated as potential therapeutic target, since it is considered a tumor-specific antigen, The objective of this project is to develop EGFR-targeted IONPs to improve the delineation of tumor outlines through targeted delivery of this MRI contrast agent to tumor cells. In addition, dual-labeling of the nanoplatform with near infrared fluorescent probes is expected to permit intra-operative optical imaging of infiltrative tumor cells, thereby decreasing the number of residual cancer cells left after surgical resection. To date antibodies have been the most successful targeting ligands and several immunoconjugates are already approved for molecular imaging in humans. However, small overall size (<100 nm) of the nanoparticle is crucial for achieving extended blood circulation times and high tumor penetration. Therefore, the use of smaller antibody fragments instead of the entire immunoglobulin molecule is preferred. In this study, I characterized novel anti-EGFR single domain antibodies (sdAbs) for their application as targeting moieties for nanoparticulate contrast agents. I determined the specificity and binding kinetics of these sdAbs for their targets EGFR and EGFRvIII using surface plasmon resonance (SPR) biosensor analysis and cell-based assays. I then conjugated the sdAbs to the surface of commercial IONPs and, after thorough investigation of the physical properties, I tested the tumor-targeting ability of these immuno-IONPs in a glioblastoma xenograft model. My findings are in agreement with published observations on the in vivo distribution of targeted superparamagnetic iron oxide nanoparticles. Modern SPR biosensors also allow the assessment of not only the binding affinity and kinetics, but also the thermodynamic parameters of protein-protein interactions. I therefore extended the use of this technology to study the interaction of a selected anti-EGFR sdAb with the extracellular domain of EGFR (EGFR-ECD), and compared this to binding of its natural ligand, the epidermal growth factor (EGF). I demonstrate that distinct thermodynamic driving forces govern sdAb and ligand binding to EGFR-ECD. My findings complement the available structural information and provide new insight into potential mechanisms of EGF-mediated receptor activation.
Le glioblastome multiforme est la tumeur primaire du cerveau la plus mortelle avec un taux de survie moyen des patients de 12 – 15 mois. Les efforts pour traiter le glioblastome avec de la radiothérapie ou des agents chimiothérapeutiques ont été largement inefficaces, ce qui explique pourquoi le paradigme de traitement actuel est avant tout basé sur la chirurgie. Ici, il a été démontré que l'étendue de la résection chirurgicale est corrélée avec le pronostic des patients. Chez les patients de glioblastome, l'imagerie par résonance magnétique (IRM) est utilisée dans le diagnostic, durant la chirurgie guidée par IRM, et pour le suivi de la progression de la maladie. Les nanoparticules superparamagnétiques d'oxyde de fer (IONPs) reçoivent actuellement une attention accrue comme agents de contraste en IRM pour l'imagerie cérébrale. Leurs propriétés de relaxation des protons, leur biocompatibilité et leur temps de rétention sont supérieurs aux agents de contraste à base de gadolinium couramment employée. En outre, leur surface plus grande permet la conjugaison des agents de ciblage et/ou étiquettes utilisées pour l'imagerie multimodale. Une des altérations génétiques les plus fréquentes dans le glioblastome primaire implique le récepteur du facteur de croissance épidermique (EGFR), sa surexpression est observée dans 50 – 71% des patients et parmi ceux-ci l'expression simultanée de mutants EGFR est fréquemment observé. La mutation la plus fréquente est la délétion de l'exon 2 – 7 de domaine extracellulaire, ce qui rend le EGFR insensible au ligand, et mène à l'activation constitutive de la kinase intracellulaire. Ce mutant est connu sous le nom EGFRvIII. L'objectif de ce projet est de développer des IONPs spécifiques pour l'EGFR afin d'améliorer la délimitation des contours de la tumeur grâce à l'administration d'agents de contraste IRM ciblée vers les cellules tumorales. En outre, le double-étiquetage de cette nanoplateforme avec des sondes fluorescentes proche infrarouge permettra l'imagerie optique intraopératoire des cellules tumorales infiltrantes aidant à une résection chirurgicale plus précise et ainsi diminuant le nombre de cellules cancéreuses résiduelles après l'opération. La petite taille globale (<100 nm) de la nanoparticule permet d'atteindre une circulation sanguine prolongée et une pénétration tumorale élevée. Dans cette étude, j'ai caractérisé des fragments d'anticorps contre l'EGFR pour leur application comme unité de ciblage et pouvant potentiellement servir comme agents de contraste nanoparticulaire. J'ai déterminé par résonance plasmonique de surface (SPR) et dans des tests cellulaires la spécificité et la cinétique de liaison de ces anticorps à domaine unique pour leurs cibles EGFR ainsi que pour le mutant EGFRvIII. J'ai ensuite conjugué ces anticorps à domaine unique sur la surface de IONPs commerciales et, après analyse approfondie de leurs propriétés physiques, j'ai testé la capacité de ciblage tumoral de ces immuno-IONPs dans un modèle de xénogreffe de glioblastome. Mes conclusions sont en accord avec les observations publiées sur la distribution in vivo des nanoparticules superparamagnétiques d'oxyde de fer ciblés. Les biocapteurs SPR modernes permettent également la détermination des paramètres thermodynamiques pour les interactions protéine-protéine. J'ai donc utilisé cette technologie pour étudier l'interaction d'un anticorps à domaine unique contre l'EGFR avec le domaine extracellulaire de l'EGFR (EGFR-ECD) en comparaison à la liaison avec son ligand naturel, le facteur de croissance épidermique (EGF). J'ai démontré que des forces motrices thermodynamiques distinctes conduisent l'interaction d'EGFR-ECD avec l'anticorps en comparaison d'avec le ligand. Mes conclusions sont en accord avec les informations structurelles disponibles et fournissent un nouvel éclairage sur les mécanismes potentiels de l'activation du récepteur par l'EGF.

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24

Harris, Linda Ann. "Polymer Stabilized Magnetite Nanoparticles and Poly(propylene oxide) Modified Styrene-Dimethacrylate Networks." Diss., Virginia Tech, 2002. http://hdl.handle.net/10919/27547.

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Magnetic nanoparticles that display high saturation magnetization and high magnetic susceptibility are of great interest for medical applications. Nanomagnetite is particularly desirable because it displays strong ferrimagnetic behavior, and is less sensitive to oxidation than magnetic transition metals such as cobalt, iron, and nickel. Magnetite nanoparticles can be prepared by co-precipitating iron (II) and iron (III) chloride salts in the presence of ammonium hydroxide at pH 9-10. One goal of this work has been to develop a generalized methodology for stabilizing nanomagnetite dispersions using well-defined, non-toxic, block copolymers, so that the resultant magnetite-polymer complexes can be used in a range of biomedical materials. Hydrophilic triblock copolymers with controlled concentrations of pendent carboxylic acids were prepared. The triblock copolymers contain carboxylic acids in the central urethane segments and controlled molecular weight poly(ethylene oxide) tail blocks. They were utilized to prepare hydrophilic-coated iron oxide nanoparticles with biocompatible materials for utility in magnetic field guidable drug delivery vehicles. The triblock copolymers synthesized contain 3, 5, or 10 carboxylic acids in the central segments with Mn values of 2000, 5000 or 15000 g/mol poly(ethylene oxide) tail blocks. A method was developed for preparing ~10 nm diameter magnetite surfaces stabilized with the triblock polymers. The carboxylic acid is proposed to covalently bind to the surface of the magnetite and form stable dispersions at neutral pH. The polymer-nanomagnetite conjugates described in this thesis have a maximum of 35 wt. % magnetite and the nano-magnetite particles have an excellent saturation magnetization of ~66 - 78 emu/g Fe3O4. Powder X-ray diffraction (XRD) confirms the magnetite crystal structure, which appears to be approximately single crystalline structures via electron diffraction spectroscopy analysis (EDS). These materials form stable magnetic dispersions in both water and organic solvents.
Ph. D.

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25

Domenici, V., S. Dolci, G. Pampaloni, and Z. Jaglicic. "New Ultra Small Iron-Oxide Nanoparticles with Titanium-Carbamate Coating: Preparation and Magnetic Properties." Thesis, Sumy State University, 2012. http://essuir.sumdu.edu.ua/handle/123456789/35456.

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This work deals with the preparation and chemical characterization of new Ultra-Small Iron-Oxide Superparamagnetic Nanoparticles (USPIONs) functionalized with Titanium-carbamate. The synthesis was performed starting from oleate-coated and 2-pyrrolidone-coated USPIONs having a maghemite ( -Fe2O3) and magnetite (Fe3O4) crystalline core, respectively. Zero-field-cooled (ZFC) and field-cooled (FC) magnetic susceptibility curves as well as the magnetization behavior as a function of temperature are reported and discussed in view of the superparamagnetic properties and coating effect of these new magnetic nanoparticles. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/35456

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26

Marinescu, Marilena Ioana. "Multimodal characterization of superparamagnetic particles of iron oxide for inflammation imaging : application to experimental cerebral ischemia." Phd thesis, Université Claude Bernard - Lyon I, 2012. http://tel.archives-ouvertes.fr/tel-00994167.

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Several studies on small animals have shown that MRI enhanced with nanoparticles of iron oxide (USPIO) is able to detect the neuroinflammation. However, to our knowledge, no team had yet investigated the potential of this approach for monitoring an anti-inflammatory treatment. In this context, we have demonstrated the feasibility of this approach to monitor the effects of minocycline after cerebral ischemia in mice. MRI is a very sensitive technique for the detection of iron, but the precise location of USPIO as well as their quantification is difficult. We therefore propsed to complete the MRI approach by a new technique to our knowledge in the field of USPIO imaging in the brain : Synchrotron radiation tomography. We here present the first results showing the feasibility of this approach and a comparative study of the sensitivity of two techniques used for the detection of USPIO in the brain. In the last part of our work, we report our results on the biotransformation of USPIOs in the spleen of the mouse during the first 40 days after intravenous injection obtained by transmission electron microscopy (TEM).

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27

Mahajan, Ujwal Mukund [Verfasser]. "Tumor specific delivery of siRNA coupled superparamagnetic iron oxide nanoparticles, targeted against Polo-like kinase 1, stops progression of pancreatic ductal adenocarcinoma / Ujwal Mukund Mahajan." Greifswald : Universitätsbibliothek Greifswald, 2016. http://d-nb.info/1082561886/34.

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Mühlberger, Marina [Verfasser], Geoffrey [Akademischer Betreuer] Lee, and Geoffrey [Gutachter] Lee. "Functionalization of T lymphocytes with superparamagnetic iron oxide nanoparticles for magnetically controlled enhancement of local anti-tumor response / Marina Mühlberger ; Gutachter: Geoffrey Lee ; Betreuer: Geoffrey Lee." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/121534323X/34.

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29

Figge, Lena. "Synthese molekularer Bildgebungssonden für die molekulare Magnetresonanztomographie." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät, 2014. http://dx.doi.org/10.18452/16992.

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Zweck der molekularen Bildgebung ist es, biologische Prozesse auf zellulärer und molekularer Ebene zu messen und zu charakterisieren, um so die Ursachen von Krankheiten und Veränderungen im Organismus zu diagnostizieren. Sie basiert auf dem Einsatz molekularer Bildgebungssonden, welche einen spezifischen biologischen Vorgang darstellen oder sich spezifisch in dem zu untersuchenden Gewebe anreichern oder aktiviert werden. Ziel dieser Arbeit war die Entwicklung und Analyse neuer Bildgebungssonden für die spezifische in-vivo-Bildgebung der Apoptose und von Enzymaktivitäten mittels Magnetresonanztomographie (MRT) auf der Grundlage sehr kleiner Eisenoxidnanopartikel (very small iron oxide particles, VSOP). VSOP sind superparamagnetisch und durch ihre negativ geladene Citrathülle elektrostatisch stabilisiert. Für die Apoptose-Bildgebung sollte durch Bindung des Proteins Annexin A5 (AnxA5) an die Citrathülle der VSOP eine zielgerichtete Sonde hergestellt werden (AnxA5-VSOP). Für die Bildgebung von Enzymaktivitäten sollte eine durch die Matrixmetalloproteinase-9 (MMP-9) aktivierbare Sonde hergestellt werden (Protease-spezifische Eisenoxidpartikel, PSOP).
The goal of molecular imaging is to characterize and measure biological processes at cellular and molecular levels for the purpose of diagnosing the cause of diseases and molecular abnormalities. Molecular imaging is based on the use of probes with a high affinity to the target tissue and / or which are specifically activated. The aim of this study was to develop and analyze new molecular imaging probes for the in vivo imaging of apoptosis and enzyme activity using magnetic resonance imaging (MRI), based on very small iron oxide particles (VSOP). VSOP are superparamagnetic and electrostatically stabilized due to their negatively charged citrate surface. For the imaging of apoptosis the protein annexin A5 (AnxA5) was coupled to the citrate surface (AnxA5-VSOP). For the imaging of enzyme activities an activatable imaging probe with a cleavage site for the matrix metalloproteinase 9 (MMP-9) was synthesized (protease-specific iron oxide particles, PSOP).

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30

Faure, Bertrand. "Particle interactions at the nanoscale : From colloidal processing to self-assembled arrays." Doctoral thesis, Stockholms universitet, Institutionen för material- och miljökemi (MMK), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-79129.

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Nanostructured materials are the next generation of high-performance materials, harnessing the novel properties of their nanosized constituents. The controlled assembly of nanosized particles and the design of the optimal nanostructure require a detailed understanding of particle interactions and robust methods to tune them. This thesis describes innovative approaches to these challenges, relating to the determination of Hamaker constants for iron oxide nanoparticles, the packaging of nanopowders into redispersible granules, the tuning of the wetting behavior of nanocrystals and the simulation of collective magnetic properties in arrays of superparamagnetic nanoparticles. The non-retarded Hamaker constants for iron oxides have been calculated from their optical properties based on Lifshitz theory. The results show that the magnitude of vdW interactions in non-polar solvents has previously been overestimated up to 10 times. Our calculations support the experimental observations that oleate-capped nanoparticles smaller than 15 nm in diameter can indeed form colloidally-stable dispersions in hydrocarbons. In addition, a simple procedure has been devised to remove the oleate-capping on the iron oxide nanoparticles, enabling their use in fluorometric assays for water remediation, with a sensitivity more than 100 times below the critical micelle concentration for non-ionic surfactants. Nanosized particles are inherently more difficult to handle in the dry state than larger micron-sized powders, e.g. because of poor flowability, agglomeration and potential toxicity. The rheology of concentrated slurries of TiO2 powder was optimized by the addition of sodium polyacrylate, and spray-dried into fully redispersible micron-sized granules. The polymer was embedded into the granules, where it could serve as a re-dispersing aid. Monte Carlo (MC) simulations have been applied to the collective magnetic behavior of nanoparticle arrays of various thicknesses. The decrease in magnetic susceptibility with the thickness observed experimentally was reproduced by the simulations. Ferromagnetic couplings in the arrays are enhanced by the finite thickness, and decrease in strength with increasing thickness. The simulations indicate the formation of vortex states with increasing thickness, along with a change in their orientation, which becomes more and more isotropic as the thickness increases.

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.

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Gautier, Juliette. "Nanoparticules d'oxydes de fer PEGylées pour la délivrance de la doxorubicine : développement et évaluation de leur potentiel théragnostique." Thesis, Tours, 2013. http://www.theses.fr/2013TOUR3805/document.

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Des nanoparticules d’oxydes de fer superparamagnétiques (SPIONs) PEGylées ont servi de plateforme pour la formulation de nanovecteurs théragnostiques pour la délivrance d’un agent anticancéreux, la doxorubicine (DOX). Le chargement de la DOX sur les nanovecteurs à l’aide d’un complexe avec l’ion fer (II) a été optimisé. Ce complexe se dissocie en milieu acide, typique des compartiments intracellulaires. La spectroscopie Raman exaltée de surface (SERS) a confirmé que les nanovecteurs libèrent la DOX sous forme non complexée. La cytotoxicité in vitro induite par la libération de la DOX a été évaluée sur différentes lignées cellulaires de cancer du sein, et comparée à celle de la DOX en solution. Les voies d’internalisation des nanovecteurs ont été explorées en microscopie électronique en transmission (MET), et le devenir intracellulaire de la DOX a été suivi en imagerie confocale multispectrale (ICMS). Enfin, un protocole thérapeutique in vivo chez la souris tumorisée a permis d’évaluer la capacité de la nanoformulation à limiter la croissance tumorale, la possibilité d’un ciblage magnétique, et la réduction des effets secondaires induits par la DOX
PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) were used as a platform to build theranostic nanovectors for the delivery of an anticancer drug, doxorubicin (DOX). The DOX loading on nanocarriers via a DOX-iron (II) complex was optimized. The complex dissociates at low pH, typical of intracellular compartments. Surface enhanced Raman scattering (SERS) confirmed that the nanovectors released DOX under free form. In vitro cytotoxicity due to DOX loaded on nanocarriers was performed on different breast cancer cells, and compared to that of DOX in solution. Internalization pathways of nanovectors were explored with transmission electron microscopy (TEM), and intracellular fate of DOX was monitored by confocal spectral imaging (CSI). To finish, a therapeutical protocol was performed on tumorized mice, in order to evaluate the efficacy of the nanoformulation on tumor reduction, the possibility of magnetic targeting, and the decrease of side effects induced by DOX

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Nagle, Irène. "Magnetic approaches for tissue mechanics and engineering of the skeletal muscle." Electronic Thesis or Diss., Université Paris Cité, 2023. http://www.theses.fr/2023UNIP7079.

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La thèse est centrée sur les propriétés mécaniques macroscopiques de tissus modèles. L'incorporation de nanoparticules super-paramagnétiques (maghémite) au cœur des cellules permet à la fois leur manipulation à distance pour créer des agrégats multicellulaires de forme contrôlée et l'application de forces pour mesurer leurs propriétés mécaniques ou induire leur organisation. Les cellules modèles choisies sont des précurseurs de muscle de souris (C2C12), pour une application directe à la mécanique et à l'ingénierie du muscle squelettique. Les déformations des agrégats formés magnétiquement et soumis par la suite à un gradient de champ magnétique permettent de mesurer leurs propriétés mécaniques macroscopiques (tension de surface, module d'Young). Nous avons ainsi pu étudier l'interaction entre les propriétés de la cellule individuelle (adhésions intercellulaires, structure et tension de l'actine) et les propriétés mécaniques à l'échelle du tissu, mettant notamment en évidence l'importance de la désorganisation de la desmine pour la rigidité et la tension de surface macroscopique. En utilisant des cellules exprimant une desmine mutée (mutation ponctuelle présente chez des patients souffrant de desminopathie), nous avons souligné le rôle fondamental de l'architecture du réseau de filament intermédiaire dans ce tissu modèle 3D. Les forces magnétiques ont ensuite été utilisées pour aider la différenciation en cellules musculaires en favorisant leur alignement et en permettant leur stimulation mécanique. Pour ce faire, nous avons développé un étireur magnétique qui étire des agrégats multicellulaires de cellules précurseurs de muscles placées entre deux aimants mobiles et favorise leur différenciation en cellules musculaires alignées. Ce dispositif représente un outil innovant pour étudier les déformations cellulaires sous étirement et la différenciation musculaire
The thesis is focused on the macroscopic mechanical properties of tissue models. The incorporation of superparamagnetic nanoparticles (maghemite) into the cells enables both their manipulation at distance to create multicellular aggregates of controlled shape and the application of forces to measure their mechanical properties or induce their organization. The cellular model chosen is a mouse muscle precursor cell line (C2C12), for a direct application to tissue mechanics and tissue engineering of the skeletal muscle. The deformations of the aggregate formed magnetically and then submitted to a magnetic field gradient enable to measure its macroscopic mechanical properties (surface tension, Young's modulus). We could therefore look at the interplay between the individual cell properties (cell-cell adhesions, actin structure and tension) and the mechanical properties at the tissue scale revealing the importance of desmin disorganization in macroscopic rigidity and surface tension. By using desmin-mutated muscle precursor cells (point mutations involved in desminopathies), we enhanced the fundamental role of the intermediate filament network architecture in this 3D tissue model. Magnetic forces were then used to promote differentiation into muscular cells by first reproducing their alignment and secondly mechanically stimulating them. To that end, we developed a magnetic stretcher to stretch multicellular aggregates of muscle precursor cells trapped between two mobile magnets and induce their differentiation into aligned muscular cells. This magnetic stretcher represents a new tool to study cell deformation under stretching and muscle cell differentiation

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33

Kohler, Nathan. "Superparamagnetic nanoparticles for cancer diagnostics and therapeutics /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/10565.

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34

Williams, Charles D. H. "Some magnetic effects of clustering in iron doped magnesium oxide." Thesis, Durham University, 1987. http://etheses.dur.ac.uk/6606/.

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The growth of a magnesioferrite precipitate in iron doped (˜lOOOOppm wt.) magnesium oxide crystals, heat treated at 973K in oxygen, is studied with torque, magnetisation and magnetic resonance measurements. The torque and magnetisation results are in agreement with a model which assumes that the precipitate grows by diffusion limited Ostwald ripening.The effects of the particle size distribution and cubic magnetocrystalline anisotropy of the orientated octahedral precipitate particles on the magnetisation and torque curves are calculated. A magnetometrie demagnetisation tensor is defined for assemblies of orientated dipoles, its variation with the assembly size is investigated and used to calculate the longitudinal demagnetisation factors of octahedra. The ferromagnetic resonance spectra obtained were not in agreement with the generally used theory of de Biasi and Devezas (J. Appl. Phys. (1978)49, 2466). A new theory, based on a spin Hamiltonian, of the FMR response of an anisotropic superparamagnet is proposed and compared with some of the experimental spectra.

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Namkung, Sook. "Superparamagnetic Iron Oxide (SPIO)-enhanced Liver MR Imaging with Ferucarbotran." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-59668.

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Chopard-Lallier, Sophie. "Suivi fonctionnel de la greffe d'îlots de Langerhans : interêt de l'imagerie IRM et de l'immuno-monitoring cellulaire." Thesis, Besançon, 2013. http://www.theses.fr/2013BESA3001.

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La greffe d'îlots de Langerhans permet de traiter le diabète de type 1 en restituant une insuline-sécrétion. La moitié des patients reprend l'insuline dans les 5 ans. Cette perte de fonction s'explique par l'absence d'outils de monitoring. Le but de notre travail était de déterminer l'efficacité de l'IRM à diagnostiquer un rejet de greffe, et d'évaluer l'intérêt du monitoring cellulaire chez les patients.Imagerie IRM chez le ratMéthodes : Des îlots syngéniques, allogéniques ou xénogéniques ont été greffés par voie intra-portale à des rats diabétiques après marquage avec une nanoparticule de fer (ferucarbotran). Les IRM étaient réalisées dans une IRM clinique 3T.Résultats : La décroissance du signal était différente suivant les 3 types de greffes. Le signal IRM des greffes allogéniques était significativement plus bas à J4 alors que la glycémie était normale. En prenant un seuil de 84% à J4, l'IRM permet d'obtenir une sensibilité de 91% et une spécificité de 70% Innnuno-monitoring cellulaireMéthodes : Des réactions lymphocytaires mixtes étaient réalisées entre les PBMC des patients greffés, et les splénocytes des donneurs. La réaction immunitaire était évaluée par la sécrétion d'IFNy (ELISpot), par la prolifération cellulaire (cytométrie du flux du Ki67), et par le dosage des cytokines (Bioplex). Le résultat était corrélé à la fonction du greffon évaluée par le (3-score).Résultats : Les patients avec une mauvaise fonction montraient une plus grande réactivité anti-donneur avec l'ELISpot IFNy (p=0,007, r=-0,50) et l'index de prolifération (p=0,006, r=-0,51). Les patients avec une mauvaise fonction avaient des taux d'IFNy, IL-5 et IL-17 plus élevés
Langerhans islet transplantation allows curingtype 1 diabetes by restoring an endogenous insulin secretion. Halfof patients will resume insulin withinyears. This loss of function may be explained by the lack of monitoring tools able to diagnose an ongoing graft failure. The aims of our work were toevaluate the efficiency of MRI to diagnose islet graft rejection, and to assess the feasibility of immune cellular monitoring in transplanted patients.MRI in the rat mortelMethods: Syngeneic, allogeneic and xenogeneic islets were transplanted intra-portally to diabetic rats after labeling with superparamagnetic ironoxide nanoparticles (ferucarbotran). Images were acquired on a clinical 3T MRI scanner.Results: The signal decreasing was different between the 3 types of transplantations. At day 4, the MRI signal in allogeneic group was significantlylower while glycaemia remained normal. With a cut-off value of 84% at day 4, sensitivity of 91% and specificity of 70% were obtained.Cellular immune monitoringMethods: Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients and splenocytes from donors. Immunereactivity was assessed by the release of IFNy (ELISpot), cell prolifération (flow cytometry of Ki67), and cytokine quantification (Bioplex). Theresults were correlated to the islet graft function assessed by (5-score.Results: Patients with low islet function showed higher cellular reactivity against donor cells assessed by ELISpot IFNy ((p=0,007, r=-0,50) andproliferation index (p=0,006, r=-0,51). Patients with low graft function had higher levels of IFNy, IL-5 and 1L-17

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Kumar, Kritika. "Microfluidic synthesis of superparamagnetic iron oxide nanocrystals for magnetic resonance imaging." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/18809.

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Superparamagnetic iron oxide nanoparticles (SPIONs) are of significant interest in areas such as drug delivery, hyperthermic treatment, magnetic resonance imaging (MRI) and selective separation of biological fluids. For all these applications there is a recognised need for improved synthetic methods that are capable of yielding SPIONs of uniform size, geometry and stoichiometry. Microfluidic reactors offer an attractive route to nanoparticle synthesis due to the superior control they provide over reaction conditions and particle properties relative to traditional bulk methods. In 2002 Edel et al.1 proposed the use of microfluidic reactors for nanoparticle synthesis due to the high levels of control they provide over key reaction parameters such as temperature, reagent concentrations and reaction time. Since that report a diversity of metal, metal oxide, compound semiconductor and organic nanomaterials have been successfully synthesised in microfluidic systems. Most reports of nanoparticle synthesis in microreactors have involved single-phase mode of operation, in which continuous streams of miscible fluids are manoeuvred through microscale channels where nucleation and growth take place. Such reactors, however, are poorly suited to the synthesis of SPIONs due to their high susceptibility to fouling. An alternative approach is to use droplet-based reactors in which an immiscible liquid is injected alongside the reaction mixture, causing the latter to spontaneously divide into a series of near identical droplets. In this thesis microfluidic synthesis of SPIONs in a controlled and reproducible manner is described. This work is focussed on improving the microfluidic methods for controlled synthesis of SPIONs and utilise the produced nanoparticles directly as contrast enhancers in MR imaging. The droplet based reactions were initially performed on polydimethylsiloxane (PDMS) microfluidic devices, however on such devices, low throughput was obtained. To overcome fabrication difficulty and to increase throughput, droplet-based synthesis was performed on the capillary-based reactor.

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Nocera, Tanya Marie. "Magnetic Force Microscopy of Superparamagnetic Nanoparticles for Biomedical Applications." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1385914094.

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39

Ferjaoui, Zied. "Synthèse et caractérisation de nanoparticules magnétiques répondantes pour des applications en thérapie cancéreuse." Electronic Thesis or Diss., Université de Lorraine, 2020. http://www.theses.fr/2020LORR0013.

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Dans le cadre de cette thèse, des nanoparticules intelligentes superparamagnétiques (SPIONs) ont été développées en vue d’être utilisées comme une plateforme médicamenteuse pour la thérapie cancéreuse. Ces nanoparticules du type cœur/coquille sont obtenues à partir de la fonctionnalisation d’un cœur à la base des Fe3-δO4 par un copolymère obtenu à l’aide de la polymérisation initiée à partir de la surface d’un mélange x MEO2MA et y OEGMA (x+y=1). Une fois que leurs structures et leur comportement colloïdal dans l’eau et in-vitro sont parfaitement caractérisés ainsi que la mise en évidence de leurs propriétés thermo-répondantes, des études d’encapsulation et du relargage d’un médicament anticancer, la doxorubicine (DOX) à des températures physiologiques ont été réalisées. Des études in-vitro ont montré la non-cytotoxicité des nanoparticules seules mais lorsque les cellules cancéreuses étaient en contact avec ces mêmes systèmes chargés en DOX, la cytotoxicité était accrue. En vue du ciblage du cancer de l’ovaire et d’internalisation des nanoparticules dans les cellules, nous avons vectorisé les précédentes avec l’acide folique, ces dernières cellules sur-exprimant des récepteurs qui fixent le α du folate (FR-α). La combinaison de différentes techniques de la caractérisation à des échelles macroscopiques et nanométriques nous ont permis de conclure que nos systèmes sont capables d’encapsuler la DOX, de la relarguer d’une manière spécifique et à une température contrôlée. Par ailleurs, elles présentent des propriétés d’hyperthermie prometteuses. Dans la cadre de cette thèse, nous avons donc développé de nouveaux vecteurs de quatrième génération pour la thérapie cancéreuse
In the frame of this PhD project, smart superparamagnetic nanoparticles (SPIONs) have been developed for a further use as a drug platform for cancer therapy. These nanoparticles of core / shell type are obtained from the functionalization of a core based on Fe3-δO4 by a co- polymer obtained from the surface-initiated polymerization of a mixture xMEO2MA and yOEGMA (x + y = 1). Once their structures and their colloidal behavior in water and in-vitro perfectly characterized as well as the demonstration of their thermo-responsive properties, studies of encapsulation and release of an anti-cancer drug, the doxorubicin (DOX) at physiological temperatures were successfully obtained. In-vitro studies showed the non- cytotoxicity of the nanoparticles, but when the cancer cells were in contact the DOX-loaded NPs, the cytotoxicity was increased. To induce the targeting of ovarian cancer (SKOV3 cells) and the enhancement of the internalization of nanoparticles in cells, we have functionalized the previous nanoparticles with folic acid as these last cells over-express receptors that bind folate α (FR-α ). The combination of different macroscopic and nanometric scale characterization techniques allowed us to conclude that our systems are capable of encapsulating DOX, releasing it in a specific manner and at a controlled rate and that they exhibit hyperthermia properties. We have then contributed to successfully develop new third generation vectors for cancer therapy

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40

Zhang, Lei 1970. "Sol-gel matrix-mediated synthesis of superparamagnetic iron oxide clusters and supported iron porphyrin oxidation catalysts." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/9968.

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Carenza, Elisa. "Engineering Iron Oxide Nanoparticles For Angiogenic Therapies." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/284861.

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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.

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42

Stuart, Dale. "Heat Transfer Enhancement using Iron Oxide Nanoparticles." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/425.

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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.

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43

Salazar, Alvarez German. "Synthesis, characterisation and applications of iron oxide nanoparticles." Doctoral thesis, KTH, Materials Science and Engineering, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-87.

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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.

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44

Zurkiya, Omar. "Magnetic Resonance Molecular Imaging Using Iron Oxide Nanoparticles." Diss., Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/19848.

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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.

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45

Salazar-Alvarez, German. "Synthesis, characterisation and applications of iron oxide nanoparticles /." Stockholm, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-87.

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46

Harris, Steven Scott. "Adiabatic pulse preparation for imaging iron oxide nanoparticles." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/47555.

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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.

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47

Chen, Suelin Ph D. Massachusetts Institute of Technology. "Polymer-coated iron oxide nanoparticles for medical imaging." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/59004.

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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.

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48

Abushrida, Ahmed. "Formulation of novel polymer coated iron oxide nanoparticles." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12537/.

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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.

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49

Requejo-Roque, Katherinne Isabel. "Iron oxide nanoparticles stable in the human body?" Revista de Química, 2013. http://repositorio.pucp.edu.pe/index/handle/123456789/101184.

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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.

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50

Roller, Jonathan William. "Arsenic mobilization through bioreduction of iron oxide nanoparticles." Thesis, Virginia Tech, 2004. http://hdl.handle.net/10919/10066.

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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

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