Дисертації: "Hyperthermia cancer magnetic field"

1

Lukawska, Anna Beata. "THERMAL PROPERTIES OF MAGNETIC NANOPARTICLES IN EXTERNAL AC MAGNETIC FIELD." Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1401441820.

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2

Hallali, Nicolas. "Utilisation de nanoparticules magnétiques dans les traitements anti-tumoraux : Au-delà de l'hyperthermie magnétique." Thesis, Toulouse, INSA, 2016. http://www.theses.fr/2016ISAT0025/document.

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Deux approches potentiellement anti-tumorales, employant des nanoparticules magnétiques (NPMs) et des champs magnétiques oscillants, furent étudiées. La première, l’hyperthermie magnétique, utilise l’échauffement de NPMs au contact des cellules tumorales provoqué par un champ magnétique alternatif haute-fréquence. Durant cette thèse, il fut démontré que les forces magnéto-mécaniques induites par les inhomogénéités de champ magnétique pendant un essai d’hyperthermie magnétique n’avaient aucune influence sur la viabilité cellulaire. Egalement, des mesures magnétiques, d’XPS, et de puissance de chauffe de NPMs de fer enrobées d’une coquille de silice amorphe furent effectuées et analysées. Il fut observé que cette coquille permettait de préserver les propriétés magnétiques des NPMs suite à l’exposition à un environnement aqueux. La deuxième approche anti-tumorale utilise des NPMs soumises à un champ magnétique basse-fréquence, induisant une stimulation mécanique des cellules tumorales. Une étude théorique complète de l’influence du champ magnétique, de l’agitation thermique et des interactions magnétiques sur la force magnéto-mécanique exercée par des NPMs, fut effectuée. Elle démontra notamment que cette force augmente de manière drastique pour une assemblée de NPMs lorsque la rotation du champ magnétique induit une rupture de symétrie dans l’évolution temporelle du couple magnéto-mécanique. Expérimentalement, il fut développé différents prototypes de génération de champ magnétique tournant à basse fréquence. Des tests in vitro furent réalisés en utilisant des NPMs enrobées par une matrice de phosphatidylcholine, leur permettant d’être solidaires des membranes cellulaires. Suite à la rotation d’un champ magnétique de 40 ou 380 mT, à 10 Hz, il fut observé une réduction de la survie cellulaire
Two anti-tumor treatments based on magnetic nanoparticles (MNPs) and oscillating magnetic field were studied. The first one, magnetic hyperthermia, uses the heat released by MNPs in contact with tumor cells under a high frequency alternating magnetic field. We have shown that the forces induced by magnetic field inhomogeneity during magnetic hyperthermia essay no influence on cellular viability. Moreover, magnetic measurements, XPS characterization and heating power evaluation of iron MNPs coated by amorphous silica shell were carried out. It was observed that this shell is able to preserve the MNP magnetic properties submitted to an aqueous environment. The second anti-tumor treatment combines MNPs and low-frequency magnetic field, inducing mechanical stress to tumor cells. A complete theoretical study on the influence of magnetic field, thermal agitation and magnetic interaction on the magneto-mechanical forces generated by the MNPs was carried out. It was demonstrated that for a MNP assembly this force increases dramatically when the rotation of the magnetic field induces a break of time reversal symmetry on the magneto-mechanical torque. Experimentally, several devices generating low frequency rotating magnetic fields were developed. Using these devices, in-vitro essays were also achieved using phosphatidylcholine coated MNPs, which bind to cellular membranes. An application of a 40 or 380 mT magnetic field rotating at 10 Hz reduced cell survival rate

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3

Nemati, Porshokouh Zohreh. "Novel Magnetic Nanostructures for Enhanced Magnetic Hyperthermia Cancer Therapy." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6548.

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In this dissertation, I present the results of a systematic study on novel multifunctional nanostructure systems for magnetic hyperthermia applications. All the samples have been synthesized, structurally/magnetically characterized, and tested for magnetic hyperthermia treatment at the Functional Materials Laboratory of the University South Florida. This work includes studies on four different systems: (i) Core/shell Fe/γ-Fe2O3 nanoparticles; (ii) Spherical and cubic exchange coupled FeO/Fe3O4 nanoparticles; (iii) Fe3O4 nano-octopods with different sizes; (iv) High aspect ratio FeCo nanowires and Fe3O4 nanorods. In particular, we demonstrated the enhancement of the heating efficiency of these nanostructures by creating monodisperse and highly crystalline nanoparticles, and tuning their magnetic properties, mainly their saturation magnetization (MS) and effective anisotropy, in controlled ways. In addition, we studied the influence of other parameters, such as the size and concentration of the nanoparticles, the magnitude of the applied AC magnetic field, or different media (agar vs. water), on the final heating efficiency of these nanoparticles. For the core/shell Fe/γ-Fe2O3 nanoparticles, a modest heating efficiency has been obtained, resulting mainly from the strong reduction in MS caused by the shrinkage of the core with time. However, for sizes above 14 nm, the shrinkage process is much slower and the obtained heating efficiency is better than the one exhibited by conventional solid nanoparticles of the same size. In the case of the exchange-coupled FeO/Fe3O4 nanoparticles, we successfully created two sets of comparable particles: spheres with 1.5 times larger MS than the cubes, and cubes with 1.5 times larger effective anisotropy than the spheres, while keeping the other parameters the same. Our results show that increasing the effective anisotropy of the nanoparticles gives rise to a greater heating efficiency than increasing their MS. The Fe3O4 nano-octopods, with enhanced surface anisotropy, present better heating efficiency than their spherical and cubic nanoparticles, especially in the high field region, and we have shown that by tuning their size and the effective anisotropy, we can optimize their heating response to the applied AC magnetic field. For magnetic fields, smaller than 300−400 Oe we found that the smallest nano-octopods give the best heating efficiency. Yet if we increase the AC field value, the bigger octopods show an increased heating efficiency and become more effective. Finally, the FeCo nanowires and Fe3O4 nanorods exhibit enhanced heating efficiency with increasing aspect ratio when aligned in the direction of the applied AC magnetic field, due to the combined effect of shape anisotropy and dipolar interactions. Of all the studied systems, these 1D high aspect ratio nanostructures have displayed the highest heating rates. All of these findings point toward an important fact that tuning the structural and magnetic parameters in general, and the effective anisotropy in particular, of the nanoparticles is a very promising approach for improving the heating efficiency of magnetic nanostructures for enhanced hyperthermia.

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4

Patel, Anil Pravin. "Cancer hyperthermia using gold and magnetic nanoparticles." Thesis, University of Glasgow, 2017. http://theses.gla.ac.uk/8124/.

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An estimated 12 million people worldwide are diagnosed with cancer every year, with around 17 million cancer-related deaths per year predicted by 2030 (Thun et al. 2010). Contemporary clinical treatments include surgery, chemotherapy and radiotherapy, however all vary in success and exhibit unpleasant side effects. Localised tumour hyperthermia is a moderately new cancer treatment envisaged by researchers, which exploits exclusive tumour vulnerabilities to specific temperature profiles (42-45°C) leading to cancer cell apoptosis, whilst normal tissue cells are relatively unaffected. Hyperthermia is therefore proposed as an alternative potential therapy for cancer, by delivering localised treatment to cancer cells, without the severe side effects associated with traditional therapies. This project aimed to investigate potential hyperthermic treatment of cancer cells in vitro by adopting nanomedicine principles. Inorganic nanoparticles, such as gold or iron oxide, are both capable of generating heat when appropriately stimulated, therefore both have been suggested as candidates for inducing localised tumour heating following their internalisation into cells. In this project, both gold (GNPs) and magnetic (mNPs) were individually assessed for their potential to deliver toxic thermal energy to bone cancer cells (MG63) and breast cancer cells (MCF-7). Studies were carried out both in standard 2D monolayer and in 3D tumour spheroids. When considering use in vivo, it is essential that both GNPs and mNPs are biocompatible, therefore initial studies characterised the cell viability and metabolic activity following incubation with the NPs. The NP internalisation was subsequently verified, prior to hyperthermic studies. Following hyperthermic treatment, both GNPs and mNPs were confirmed as inducing cancer cell death. Further studies were carried out using the GNPs, to identify the cell death pathways activated, where mitochondrial stress was evident following 2D culture tests. Gene and protein expression analysis indicated that cell death occurred predominantly via several apoptotic pathways, through increased fold expression changes in apoptotic markers. Interestingly, cell protective mechanisms were simultaneously switched on, as cells were also observed to exhibit thermotolerance with a number of heat shock proteins (Hsps) being substantially increased during hyperthermic treatments.

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5

Kozissnik, B. "Antibody targeted magnetic nanoparticle hyperthermia for cancer therapy." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1415747/.

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Superparamagnetic iron oxide nanoparticles (SPION) are used clinically to improve the sensitivity of magnetic resonance imaging (MRI). A less exploited property of SPION is their ability to generate heat when subjected to an alternating magnetic field, a process called magnetic alternating current hyperthermia (MACH). Hyperthermia has been shown to be a cancer effective treatment modality in the clinic when given together with radio/chemotherapy. However, delivery of sufficient heat to damage tumours without harming healthy tissue remains challenging. The central hypothesis for this thesis is that MACH activated SPION can be used to generate hyperthermia in situ and therefore will have potential to achieve localised hyperthermic cancer treatments. The aim of the thesis was to evaluate the potential of SPION to deliver localised hyperthermia by: (1) Characterization and comparison of SPION to select a lead candidate for clinical application. (2) Developing conjugation methods to confer SPION with cancer-binding properties by attachment of single chain Fv antibodies (scFv). (3) Evaluating the localisation and heating potential in vivo. SPION were characterized with regard to their hydrodynamic diameter, core size, magnetic properties, atomic iron content and heating potential for hyperthermia application. Different chemistries were evaluated to functionalize the most promising candidate using shMFEm, an scFv targeting the carcinoembryonic antigen (CEA). A CEA-non-binding scFv variant, shNFEm, was used as a negative control. Functionality of the scFv-SPIONs was assessed using quartz crystal microbalance. In vivo heating potential of the SPION was tested in a xenograft tumour model in vivo, using bespoke MACH apparatus. The results established Ferucarbotran (FX), unformulated Resovist®, an MRI contrast agent, as the most suitable candidate for hyperthermia application. Cyanogen bromide chemistry was selected to functionalise Ferucarbotran with the scFvs shMFEm. The FX-scFv conjugates were purified and analysed. Functionality was confirmed by quartz crystal microbalance, enabling the first visualisation of the interaction between a SPION-scFv conjugate and cognate antigen in real-time. The in vivo assessment of Ferucarbotran and the FX-scFv conjugates confirmed the in vitro heating potential of Ferucarbotran. In vivo analysis of heating showed that localised hyperthermia was achievable with intratumoral injection followed by MACH. Histological analysis of the tumours revealed an uneven distribution of particles within the tumours and an accumulation of the particles within the surrounding stroma indicating the future work should include study of innovative tumour delivery methods. These results support the hypothesis of a therapeutic potential for targeted magnetic nanoparticle hyperthermia and indicates the challenges that have be addressed to enable clinical application of this treatment modality.

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6

Petryk, Alicia Ailie. "Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy." Thesis, Dartmouth College, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3634608.

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Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

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7

Holladay, Robert Tyler. "Incorporating Magnetic Nanoparticle Aggregation Effects into Heat Generation and Temperature Profiles for Magnetic Hyperthermia Cancer Treatments." Thesis, Virginia Tech, 2016. http://hdl.handle.net/10919/64507.

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In treating cancer, a primary consideration is the target specificity of the treatment. This is a measure of the treatment dose that the cancerous (target) tissue receives compared to the dose that healthy tissue receives. Nanoparticle (NP) based treatments offer many advantages for target specificity compared to other forms of treatment due to their ability to selectively target tumors. One benefit of using magnetic NPs is their ability to release heat, which can both sensitize tumors to other forms of treatment as well as damage the tumor. The work here aims to incorporate a broad range of relevant physics into a comprehensive model. NP aggregation is known to be a large source of uncertainty in these treatments, thus a framework has been developed that can incorporate the effects of aggregation on NP diffusion, NP heat release, temperature rise, and overall thermal damage. To quanitify thermal damage in both healthy tissue and tumor tissue, the Cumulative Equivalent Minutes at 43 textcelsius~model is used. The Pennes bioheat equation is used as the governing equation for the temperature rise and included in it is a source heating term due to the NPs. NP diffusion and aggregation are simulated via a random walk process, with a probability of aggregation determining if nearest neighbor particles aggregate at each time step. Additionally, models are developed that attempt to incorporate aggregation effects into NP heat dissipation, though each proves to only be accurate when there is little aggregation occurring. In this work, verification analyses are done for each of the above areas and, at minimum, qualitatively accurate results have been achieved. Verification results of this work show that aggregation can be neglected at concentrations on the order of $100~nM$ or less. This however only serves as a rough estimation and further work is needed to gain a better quantitative understanding of the effects of NP concentration on aggregation. Using this concentration as a limitation, results are presented for a variety of tumor sizes and concentration distributions. Because this work incorporates a variety of physics and numerical methods into a single encompassing model, depth and physical accuracy in each area (bio-heat transfer, diffusion via random walk, NP energy dissipation, and aggregation) have been somewhat limited. This does however provide a framework in which each of the above areas can be further developed and their effects examined in the overall course of treatment.
Master of Science

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8

Andersson, Mikael. "Modeling and characterization of magnetic nanoparticles intended for cancer treatment." Thesis, Uppsala universitet, Fasta tillståndets fysik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-199055.

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Cancer is one of the challenges for today's medicine and therefore a great deal of effort is being put into improving known methods of treatment and developing new ones. A new method that has been proposed is magnetic hyperthermia where magnetic nanoparticles linked to the tumor dissipate heat when subjected to an alternating magnetic field and will thus increase the temperature of the tumor. This method makes the tumor more susceptible to radiation therapy and chemotherapy, or can be used to elevate the temperature of the tumor cells to cause cell death. The particles proposed for this are single core and often have a size in the range of 10 nm to 50 nm. To achieve an effective treatment the particles should have a narrow size distribution and the proper size. In this work, a theoretical model for predicting the heating power generated by magnetic nanoparticles was evaluated. The model was compared with experimental results for magnetite particles of size 15 nm to 35 nm dissolved in water. The properties of the particles were characterized, including measurements of the magnetic saturation, the effective anisotropy constant, average size and size distribution. To evaluate the results from the model the AC susceptibility and heating power were experimentally determined. The model is a two-step model. First the out-of-phase component of the AC susceptibility as a function of frequency is calculated. Then this result is used to calculate the heating power. The model gives a correct prediction of the shape of the out-of-phase component of the susceptibility but overestimates its magnitude. Using the experimentally determined out-of-phase component of the susceptibility, the model estimation of the heating power compares quite well with the measured values.

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9

Kallumadil, M. "Towards a complete magnetic hyperthermia technology as a novel cancer treatment system." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1149633/.

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The subject of this thesis explores the development of magnetic hyperthermia technology at the preclinical stage. Magnetic hyperthermia uses magnetic nanoparticles as functionalisable agents, targeted to cancer sites. They can then be non-invasively activated by alternating magnetic fields to deliver lethal doses of heat to the cancer cells with minimal damage to healthy tissue. This work concentrates on several complex aspects concealed within the conceptual simplicity of magnetic hyperthermia. One key aspect lies in the design of the alternating magnetic field generator. Here, a novel device, the MACH system, that exceeds currently available AC magnetic field generators in performance, form factor and versatility is described and evaluated. Electronic characteristics for 5 different configurations, ranging from a solenoidal to a flat applicator, are presented. Furthermore, magnetic field distributions in and around the applicator coil were modeled for all real configurations and two hypothetical models. These models revealed that in certain configurations high magnetic field gradients exist, prompting careful positioning of samples in real experiments. Sixteen commercially available iron-oxide nanoparticles with potential as hyperthermia candidates were characterised using photon correlation spectroscopy, atomic emission spectroscopy, asymmetric field-flow fractionation, spectrophotometric iron trace analysis, calorimetric analysis and magnetometry. To compare the heating rates of nanoparticle samples, a new design rule parameter, the intrinsic loss parameter (ILP), was introduced to replace the status quo, the equipment-dependent specific absorption rate (SAR). The results highlight a magnetic crystal size dependence with ILP, and also imply that some commercial samples are approaching the best achievable results. Finally, the commercial potential of the MACH system is evaluated in light of new applications that exploit its unique, distinguishing features. Hyperthermia cancer treatment was concluded to have the greatest potential on the long run, with the adhesives and thermoset polymer industry being lucrative short-term targets.

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10

UEDA, MINORU, MASAAKI MATSUI, TATSUYA KOBAYASHI, KENJI MITSUDO, YASUSHI HAYASHI, and IWAI TOHNAI. "THERMOCHEMOTHERAPY FOR CANCER OF THE TONGUE USING MAGNETIC INDUCTION HYPERTHERMIA (IMPLANT HEATING SYSTEM : IHS)." Nagoya University School of Medicine, 1996. http://hdl.handle.net/2237/16101.

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11

Winter, Lukas. "Detailing radio frequency controlled hyperthermia and its application in ultrahigh field magnetic resonance." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://dx.doi.org/10.18452/17012.

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Die vorliegende Arbeit untersucht die grundsätzliche Machbarkeit, Radiofrequenzimpulse (RF) der Ultrahochfeld (UHF) Magnetresonanztomographie (MRT) (B0≥7.0T) für therapeutische Verfahren wie die RF Hyperthermie oder die lokalisierte Freigabe von Wirkstoffträgern und Markern zu nutzen. Im Rahmen der Arbeit wurde ein 8-Kanal Sened/Empfangsapplikator entwickelt, der bei einer Protonenfrequenz von 298MHz operiert. Mit diesem weltweit ersten System konnte in der Arbeit experimentell bewiesen werden, dass die entwickelte Hardware sowohl zielgerichtete lokalisierte RF Erwärmung als auch MR Bildgebung und MR Thermometrie (MRTh) realisiert. Mit den zusätzlichen Freiheitsgraden (Phase, Amplitude) eines mehrkanaligen Sendesystems konnte aufgezeigt werden, dass der Ort der thermischen Dosierung gezielt verändert bzw. festgelegt werden kann. In realitätsnahen Temperatursimulationen mit numerischen Modellen des Menschen, wird in der Arbeit aufgezeigt, dass mittels des entwickelten Hybridaufbaus eine kontrollierte und lokalisierte thermische Dosierung im Zentrum des menschlichen Kopfes erzeugt werden kann. Nach der erfolgreichen Durchführung dieser Machbarkeitsstudie wurden in theoretischen Überlegungen, numerischen Simulationen und in ersten grundlegenden experimentellen Versuchen die elektromagnetischen Gegebenheiten von MRT und lokal induzierter RF Hyperthermie für Frequenzen größer als 298MHz untersucht. In einem Frequenzbereich bis zu 1.44GHz konnte der Energiefokus mit Hilfe spezialisierter RF Antennenkonfigurationen entscheidend weiter verkleinert werden, sodass Temperaturkegeldurchmesser von wenigen Millimetern erreicht wurden. Gleichzeitig konnte gezeigt werden, dass die vorgestellten Konzepte ausreichende Signalstärke der zirkular polarisierten Spinanregungsfelder bei akzeptabler oberflächlicher Energieabsorption erzeugen, um eine potentielle Machbarkeit von in vivo MRT bei B0=33.8T oder in vivo Elektronenspinresonanz (ESR) im L-Band zu demonstrieren.
The presented work details the basic feasibility of using radiofrequency (RF) fields generated by ultrahigh field (UHF) magnetic resonance (MR) (B0≥7.0T) systems for therapeutic applications such as RF hyperthermia and targeted drug delivery. A truly hybrid 8-channel transmit/receive applicator operating at the 7.0T proton MR frequency of 298MHz has been developed. Experimental verification conducted in this work demonstrated that the hybrid applicator supports targeted RF heating, MR imaging and MR thermometry (MRTh). The approach offers extra degrees of freedom (RF phase, RF amplitude) that afford deliberate changes in the location and thermal dose of targeted RF induced heating. High spatial and temporal MR temperature mapping can be achieved due to intrinsic signal-to-noise ratio (SNR) gain of UHF MR together with the enhanced parallel imaging performance inherent to the multi-channel receive architecture used. Temperature simulations in human voxel models revealed that the proposed hybrid setup is capable to deposit a controlled and localized RF induced thermal dose in the center of the human brain. After demonstrating basic feasibility, theoretical considerations and proof-of-principle experiments were conducted for RF frequencies of up to 1.44GHz to explore electrodynamic constraints for MRI and targeted RF heating applications for a frequency range larger than 298MHz. For this frequency regime a significant reduction in the effective area of energy absorption was observed when using dedicated RF antenna arrays proposed and developed in this work. Based upon this initial experience it is safe to conclude that the presented concepts generate sufficient signal strength for the circular polarized spin excitation fields with acceptable specific absorption rate (SAR) on the surface, to render in vivo MRI at B0=33.8T or in vivo electron paramagnetic resonance (EPR) at L-Band feasible.

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12

Jayasundar, Rama. "Magnetic resonance studies in oncology : measurement of the effects of hyperthermia on tumour pH." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335171.

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13

Gonzales-Weyhmiller, Marcela. "Synthesis, modeling, and optimization of iron oxide nanoparticles for magnetic fluid hyperthermia /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10568.

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14

Stigliano, Robert Vincent. "Development and validation of a treatment planning model for magnetic nanoparticle hyperthermia cancer therapy." Thesis, Dartmouth College, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1566731.

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The use of magnetic nanoparticles (mNPs) to induce local hyperthermia has been emerging in recent years as a promising cancer therapy, in both a stand-alone and combination treatment setting, including surgery radiation and chemotherapy. The mNP solution can be injected either directly into the tumor, or administered intravenously. Studies have shown that some cancer cells associate with, internalize, and aggregate mNPs more preferentially than normal cells, with and without antibody targeting. Once the mNPs are delivered inside the cells, a low frequency (30-300kHz) alternating electromagnetic field is used to activate the mNPs. The nanoparticles absorb the applied field and provide localized heat generation at nano-micron scales.

Treatment planning models have been shown to improve treatment efficacy in radiation therapy by limiting normal tissue damage while maximizing dose to the tumor. To date, there does not exist a clinical treatment planning model for magnetic nanoparticle hyperthermia which is robust, validated, and commercially available. The focus of this research is on the development and experimental validation of a treatment planning model, consisting of a coupled electromagnetic and thermal model that predicts dynamic thermal distributions during treatment.

When allowed to incubate, the mNPs are often sequestered by cancer cells and packed into endosomes. The proximity of the mNPs has a strong influence on their ability to heat due to interparticle magnetic interaction effects. A model of mNP heating which takes into account the effects of magnetic interaction was developed, and validated against experimental data. An animal study in mice was conducted to determine the effects of mNP solution injection duration and PEGylation on macroscale mNP distribution within the tumor, in order to further inform the treatment planning model and future experimental technique. In clinical applications, a critical limiting factor for the maximum applied field is the heating caused by eddy currents, which are induced in the noncancerous tissue. Phantom studies were conducted to validate the ability of the model to accurately predict eddy current heating in the case of zero blood perfusion, and preliminary data was collected to show the validity of the model in live mice to incorporate blood perfusion.

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Peci, Taze. "Carbon nanotubes filled with continuous ferromagnetic α-Fe nanowires and surface-functionalized with paramagnetic Gd(III) : a candidate magnetic hyperthermia structure and MRI contrast agent". Thesis, Queen Mary, University of London, 2017. http://qmro.qmul.ac.uk/xmlui/handle/123456789/31862.

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The main goal of this project was the development of carbon nanotubes as a candidate for dual-functioning magnetic hyperthermia structure and magnetic resonance imaging contrast agent. This was achieved by filling carbon nanotubes with continuous ferromagnetic α-Fe nanowires and surface functionalized with paramagnetic Gd(III). Also, length control of both nanotube and nanowire was investigated. Firstly, a low vapour flow-rate and constant evaporation temperature chemical vapour deposition method based on the thermal decomposition of ferrocene was employed which achieved continuous α-Fe nanowires on the same scale as the nanotube for lengths >10 m without the necessity of post-synthesis heat-treatment or introduction of other precursor elements. The low vapour flow-rate regime has the advantage of sustaining the intrinsic temperature gradient at the tip of the forming structure which drives the vapour feedstock to the growth front to guarantee continuous nanowire formation. For initially mixed-phase nanowires of length less than 10 μm, the continuous α-Fe nanowires were achieved by postsynthesis heat treatment. Secondly, a simple wet chemical method involving only sonication in aqueous GdCl3 solution was used for surface functionalization of iron-filled multiwalled carbon nanotubes with gadolinium. Functional groups on the sidewalls produced by the sonication provide active nucleation sites for the loading of Gd3+ ions. Characterization by electron paramagnetic resonance, electron energy loss spectroscopy, and high-resolution transmission electron microscopy confirmed the presence of Gd3+ ions on the sidewall surface. The ferromagnetic properties of the encapsulated iron nanowire maintained after surface functionalization. At room temperature a saturation magnetization of 40 emu/g and a coercivity of 600 Oe were observed. Heating functionality in an alternating applied magnetic field was quantified through the measurement of specific absorption rate: 50 W/gFe and the intrinsic loss power: 1.12 nHm²kg⁻¹ at magnetic field strength 8 kA/m and frequency of 696 kHz. These structures exhibited an extremely high relaxivity r₁ ~ 200 mM⁻¹ s⁻¹ at high magnetic field (9.4 T).

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Balivada, Sivasai. "Cell mediated therapeutics for cancer treatment: tumor homing cells as therapeutic delivery vehicles." Diss., Kansas State University, 2013. http://hdl.handle.net/2097/16890.

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Doctor of Philosophy
Department of Anatomy and Physiology
Deryl L. Troyer
Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V266ED3, rMcherry red) plasmids were constructed. Membrane anchoring and activity of designed proteins were analyzed in RAW264.7 Mo/Ma and HEK293 cells in vitro. Further, Urokinase (uPA) mediated cleavage and release of rCasp3V266ED3 from engineered cells was tested (Chapter-4). Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments. Final chapter of present report shows evidence for immune-deficient line of pigs as a model for human cancers (Chapter-5)

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17

Glazer, Evan S. "Intracellular Hyperthermia Mediated by Nanoparticles in Radiofrequency Fields in the Treatment of Pancreatic Cancer." Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/222840.

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Intracellular hyperthermic therapy may prove to be a unique and novel approach to the management of pancreatic cancer. Utilizing the principle of photothermal destruction, selective killing of cancer cells with minimal injury to normal tissues may be possible. This dissertation investigated the role of antibody targeted metal nanoparticles and the cytotoxic effects of nonionizing radiofrequency fields in pancreatic cancer. Cancer cell death was induced by heat release from intracellular metal nanoparticles after radiofrequency field exposure. Fluorescent and gold nanoparticles were delivered with two antibodies, cetuximab and PAM-4, to pancreatic cancer cells in vitro and mouse xenografts in vivo. Selective delivery of these nanoparticles induced cell death in vitro and decreased tumor burden in vivo after whole animal RF field exposure. This occurred through both apoptosis and necrosis. In addition, activated caspase-3 was increased after antibody treatment and RF field exposure. Furthermore, although there was non-specific uptake by the liver and spleen in vivo, there was no evidence of acute or chronic toxicity in the animals. These results are in agreement with the principle that malignant cells are more thermally sensitive than normal cells or tissues. Selective intracellular delivery of metal nanoparticles coupled with whole body RF field exposure may be a beneficial therapy against micrometastases and unresectable pancreatic cancer in the future. Further studies are planned with more specific antibodies, other nanoparticles, and other cancer targets.

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18

Huth, Christopher. "Development of Multifunctional Nanoparticles for Cancer Therapy Applications." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1352401861.

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19

Balivada, Sivasai. "A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles : a mouse study." Thesis, Manhattan, Kan. : Kansas State University, 2009. http://hdl.handle.net/2097/2282.

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20

Hauser, Anastasia K. "PEPTIDE-FUNCTIONALIZED MAGNETIC NANOPARTICLES FOR CANCER THERAPY APPLICATIONS." UKnowledge, 2016. http://uknowledge.uky.edu/cme_etds/59.

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Lung cancer is one of the leading causes of cancer deaths in the United States. Radiation and chemotherapy are conventional treatments, but they result in serious side effects and the probability of tumor recurrence remains high. Therefore, there is an increasing need to enhance the efficacy of conventional treatments. Magnetic nanoparticles have been previously studied for a variety of applications such as magnetic resonance imaging contrast agents, anemia treatment, magnetic cell sorting and magnetically mediated hyperthermia (MMH). In this work, dextran coated iron oxide nanoparticles were developed and functionalized with peptides to target the nanoparticles to either the extracellular matrix (ECM) of tumor tissue or to localize the nanoparticles in subcellular regions after cell uptake. The magnetic nanoparticles were utilized for a variety of applications. First, heating properties of the nanoparticles were utilized to administer hyperthermia treatments combined with chemotherapy. The nanoparticles were functionalized with peptides to target fibrinogen in the ECM and extensively characterized for their physicochemical properties, and MMH combined with chemotherapy was able to enhance the toxicity of chemotherapy. The second application of the nanoparticles was magnetically mediated energy delivery. This treatment does not result in a bulk temperature rise upon actuation of the nanoparticles by an alternating magnetic field (AMF) but rather results in intracellular damage via friction from Brownian rotation or nanoscale heating effects from Neél relaxations. The nanoparticles were functionalized with a cell penetrating peptide to facilitate cell uptake and lysosomal escape. The intracellular effects of the internalized nanoparticles alone and with activation by an AMF were evaluated. Iron concentrations in vivo are highly regulated as excess iron can catalyze the formation of the hydroxyl radical through Fenton chemistry. Although often a concern of using iron oxide nanoparticles for therapeutic applications, these inherent toxicities were harnessed and utilized to enhance radiation therapy. Therefore, the third application of magnetic nanoparticles was their ability to catalyze reactive oxygen species formation and increase efficacy of radiation. Overall, iron oxide nanoparticles have a variety of cancer therapy applications and are a promising class of materials for increasing efficacy and reducing the side effects of conventional cancer treatments.

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21

Lungaro, Lisa. "Development and utility of magnetic nanoparticles production by mammalian cells." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31074.

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Magnetic hyperthermia (MH) is an anti-cancer treatment which exploits the heat produced by tumour-targeted magnetic nanoparticles (MNPs) subjected to an alternating magnetic field (AMF). A problem limiting the clinical use of MH, however, is the inability to adequately localise the MNPs at the tumour site. A cellular approach using mesenchymal stem cells (MSCs) as carriers has been proposed as these cells are believed to home to sites of tissue injury and tumour growth, however problems with MNPs uptake and toxicity retard progress and need to be overcome. The aim of this project was to find an alternative approach in MH treatment, creating engineered human MSCs able to biosynthesise MNPs. To achieve this goal, MSCs were transfected with either, or both, M. magneticum AMB-1 mms6 and mmsF genes. M. magneticum AMB-1 is a genus of magnetotactic bacteria, containing magnetosomes, which are lipidic organelles containing single crystals of magnetite. M. magneticum-AMB1 mms6 and mmsF genes are important for final crystal morphology and are known to play a role in crystal synthesis and growth respectively. The originality of this study was in using mms6 and mmsF genes, which were codon-optimized for mammalian expression, alone or in combination, for transfection of human MSCs, which have known tumour homing capacity. The transfected MNPs-bearing MSCs, able to migrate into the tumour tissue, were subjected to AMF in MH experiments in an attempt to induce cancer cell death. mms6 and mmsF gene expression, following transfection, was investigated in the human osteosarcoma cell line MG63 by reverse transcription polymerase chain reaction (RT-PCR). The cellular ultrastructure of transfected MG63 cells was investigated by transmission electron microscopy (TEM), revealing the presence of nanoparticles. The magnetism of transfected MG63 cells was proved by superconducting quantum interference device (SQUID) and supported by in vitro MH experiments. Then, human MSCs were transfected with mms6 and mmsF genes, alone or in combination. The effect of transfection experiments and MNPs synthesis on MSCs markers of stemness, cell proliferation and differentiation ability were investigated. The MTB genes expression in human MSCs was assessed by RT-PCR and cell magnetism was confirmed by SQUID, in vitro MH experiments and by magnetic force microscopy (MFM). Then, in vitro studies of MH were undertaken to establish whether mms6 transfected MSCs expressing MNPs supported a MH effect when exposed to an AMF. Cells were initially exposed to an AMF of 565.3 kHz frequency in monolayers and in 3D arrangements and cell death/viability was assessed. Subsequently, the effect of the same AMF on 3D models of mixed populations of mms6-expressing MSCs and cancer cells was assessed. The results indicate that viability of MNPs-expressing MSCs and adjacent cancer cells is reduced following AMF exposure. In vivo studies of MH were undertaken following intracardiac injection of mms6-expressing MSCs in tumour-bearing mice (epidermoid carcinoma). The expression of mms6-expressing MSCs inside mice organs was confirmed by RT-PCR, fluorescence microscopy and immunohistochemistry. The effect of the application of an AMF of 565.3 kHz on mice tumours was studied with different techniques (tumour size and volume measurement, multiphoton microscopy, haematoxylin and eosin staining, and activated Caspase 3 expression), to understand if MNPs created inside mms6- expressing MSCs, following AMF exposure, could lead to cancer cell death. Results indicate that mice tolerate the treatment well, however no appreciable tumour reduction or necrosis was evident. Overall the results suggest that mms6 transfection alone confers the highest magnetisation to MSCs compared to mmsF alone or mms6+mmsF co-transfected, and that mms6 expression in human MSCs does not have an adverse effect on important cell functions. mms6-expressing MSCs, when exposed to an AMF, show reduced viability and enhanced cell cytotoxicity in vitro. When co-cultured with cancer cells in 3D models in vitro, mms6-expressing MSCs are able to reduce viability of adjacent cancer cells confirming the potential applicability of mms6- expressing MSCs for MH treatment. In vivo proof of concept experiments show that mms6-expressing MSCs can locate to the tumour tissue, and mms6-expressing intracardiac injected MSCs mice exposed to AMF tolerate the treatment well. However, the number of mms6-expressing MSCs able to localize to the tumour tissue in this experiment was too low to give an appreciable tumour reduction, so more experiments are needed to enhance the experimental protocol. A number of improvements are required to progress this novel technique towards clinical application. Gene transfection and MNPs production need to be optimised, the best frequency for MH needs to be established and MSCs delivery to the tumour has to be significantly increased to allow concentration of MNPs. The study has helped to increase our knowledge on the creation of magnetic human MSCs to potentially use these cells in MH cancer treatment.

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22

Hervault, A. M. M. "Development of a doxorubicin-loaded dual pH- and thermo-responsive magnetic nanocarrier for application in magnetic hyperthermia and drug delivery in cancer therapy." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1566981/.

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Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia has been noticed more than thirty years ago. However, combining magnetic nanoparticles with drug molecules in the same nanoformulation has only recently emerged as a promising tool for the simultaneous application of hyperthermia and chemotherapy. In this work, initial experimentation was primarily focused on the synthesis of magnetic nanoparticles of high saturation magnetisation to develop efficient mediators of heat based on an iron core and a bismuth shell. However, such nanoparticles could not be obtained due to the impossibility to grow the bismuth shell on the iron nanoparticle surface. The rest of this study reports the development of a novel magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both mediators of heat and drug carriers. The conjugation of the anticancer drug doxorubicin to the thermo-responsive MNCs via acid-cleavable imine linkers provides advanced features for the targeted delivery of doxorubicin via the combination of magnetic targeting, and dual pH- and thermo-responsive behaviour, which offers spatial and temporal control over the release of the drug. The nanoparticles exhibit a superparamagnetic behaviour with a saturation magnetization around 78 emu/g and good heating properties in an alternating magnetic field. Almost a complete doxorubicin release was obtained under acidic tumour pH and hyperthermia conditions. Finally, in vitro studies on human glioma and breast cancer cell lines and on a murine prostate carcinoma cell line confirmed that thermo-chemotherapy applied via the developed smart delivery system exhibits a substantial increase in cytotoxicity as compared to standalone therapies, and almost complete cell death was observed while applying low thermal and chemotherapeutic doses.

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23

Gilliland, Stanley E. III. "Modified Seed Growth of Iron Oxide Nanoparticles in Benzyl Alcohol: Magnetic Nanoparticles for Radio Frequency Hyperthermia Treatment of Cancer." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3611.

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Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties affecting radiofrequency heat generation. The reaction A2-24(205)_B2-24(205) produced monodispersed (PDI=0.265) nanoparticles with a crystallite size of 19.5±1.06 nm and the highest radiofrequency heating rate of 4.48 (°C/min)/mg (SAR=1,175.56 W/g, ILP=3.1127 nHm2/kg) for the reactions investigated. The benzyl alcohol modified seed growth method offers great potential for synthesizing iron oxide nanoparticles for radiofrequency hyperthermia.

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24

Lazarakis, Peter. "Effects of a static magnetic field on biological samples." School of Engineering Physics - Faculty of Engineering, 2009. http://ro.uow.edu.au/theses/3033.

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FTIR spectroscopy uses the absorbed light in an IR beam to determine the composition of a sample. This study was done using FTIR techniques to determine the damage done or alterations caused when a magnetic field was applied to a biological sample (cell cultures).The effects of magnetic fields on biological samples is an area that is not very well understood with little reliable data available.Various experiments investigating the influence of a magnetic field on cell growth, the chemical bonds in cells and the effects during irradiation were performed. Consistently it was seen that the largest changes to the cell were found in hydrogen bonds, most commonly in water. Though perhaps this may not normally create any significant biological impact when a biological sample is irradiated, as in radiotherapy, the chemical and physical structure of water is quite important.

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25

Dyne, Eric D. "Magnetic Nanoparticle Hyperthermia-Mediated Clearance of Beta-amyloid Plaques: Implications in the Treatment of Alzheimer’s Disease." Kent State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1618706341759415.

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26

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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27

Winter, Lukas [Verfasser], Thoralf [Akademischer Betreuer] Niendorf, Peter [Akademischer Betreuer] Wust, and Beate [Akademischer Betreuer] Röder. "Detailing radio frequency controlled hyperthermia and its application in ultrahigh field magnetic resonance / Lukas Winter. Gutachter: Thoralf Niendorf ; Peter Wust ; Beate Röder." Berlin : Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://d-nb.info/1054989575/34.

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28

Falqueiro, André Miotello. "Nanocápsulas contendo selol e fluído magnético: preparação, caracterização e avaliação da atividade antitumoral in vitro." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/60/60137/tde-05072012-100344/.

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O Câncer nas últimas décadas tem se tornado um evidente problema de saúde pública mundial. Os números de novos casos que surgem a cada ano e as altas taxas de mortalidade levam os pesquisadores a procurar formas de conter o avanço dessa doença. A principal forma de tratamento e que possui a maior incidência de cura é o uso de quimioterápicos, que são substâncias químicas utilizadas isoladas ou em combinação, com o objetivo de tratar as neoplasias malignas. Entretanto eles atuam sem especificidade, não destruindo seletivamente e exclusivamente as células tumorais o que causa graves efeitos colaterais aos pacientes. Com o intuito de aumentar a seletividade do tratamento, diminuir a toxicidade e aumentar o poder de cura o presente trabalho utiliza duas abordagens para o combate do câncer, a nanotecnologia (uso de sistemas de liberação de fármacos) e a hipertermia. Foram preparadas, caracterizadas e avaliadas quanto à atividade antitumoral in vitro nanocápsulas contendo o agente quimioterápico selol (composto semi-sintético provindo do óleo de girassol e que possui selênio na sua estrutura) e fluído magnético iônico (composto por nanopartículas magnéticas de maghemita, ?-Fe2O3. Ao total foram preparadas quatro diferentes formulações pelo método de nanoprecipitação descrito por Fessi com algumas modificações. As nanocápsulas apresentaram um tamanho de partícula máximo de 230,5 nm (± 4,5), com índice de polidispersividade < 0,267 (± 0,05) e potencial zeta que variou de -54,4 mV (± 3,4) a -28,6 mV (± 4,3). Foram realizadas análises da morfologia das nanocápsulas através de microscopia eletrônica de transmissão que confirmaram o tamanho nanométrico do sistema preparado. Todas as formulações demonstraram ser estáveis durante o tempo 3 meses quando armazenadas a temperatura de 4oC. Nos estudos celulares foram utilizadas as linhagens B16- F10 (melanoma murino) e OSCC (carcinoma epidermóide de boca humano), sendo que as mesmas mostraram diferentes comportamentos quando incubadas com as formulações em diferentes concentrações. Na linhagem B16-F10 foi observado um maior efeito de morte causado pelo selol (a viabilidade celular chegou a 52,5 % ± 8,4), já quando o campo magnético foi utilizado não foi possível observar um aumento da morte celular. No estudos com a linhagem OSCC, a mesma demonstrou resistência quando foi tratada com selol e na ausência de campo magnético, já quando o campo magnético foi utilizado a viabilidade celular chegou a 33,3% (± 0,3), indicando um forte efeito hipertêmico nesta linhagem. Mais estudos devem ser realizados para entendermos o efeito do sistema preparado perante diferentes linhagens celulares, no entanto podemos confirmar o sucesso no preparo do mesmo e a capacidade de causar morte de diferentes células neoplásicas, o que indica uma importante arma para atuar futuramente no combate do câncer.
In the latest decades, cancer has become a clear public health problem worldwide. The neoplastic diseases increase each year and high mortality rates lead researchers to develop new approaches able to contain the progress of this disease. The main treatment type which has the highest incidence of cure is based on chemotherapeutic agents used alone or in combination. However, they act without specificity and selectively destroying both tumor and normal cells causing serious side effects to patients. In order to enhance the selectivity of the treatment decreasing toxicity and increase the healing power, the present study employs two approaches to treat the cancer, nanotechnology (the use of drug delivery systems) and hyperthermia (magnetic fluid). Nanocapsules containing the chemotherapeutic agent selol (semi-synthetic compound coming from sunflower oil and that has selenium in its structure) and maghemite magnetic nanoparticles (?-Fe2O3) were prepared, characterized, and evaluated in respect with their in vitro antitumor activity. Four different formulations were prepared by the nanoprecipitation method described by Fessi et al. with some modifications. The nanocapsules presented a particle size up to 230.5 nm (±4.5) with polydispersity index of 0.267 (±0.05), and zeta potential ranged from - 54.4 mV (±3.4) to - 28.6 mV (±4.3). The transmission electron microscopy analysis of nanocapsules confirmed the nanometric size system prepared. All formulations proved to be stable during 3 months as stored at 4°C. The cell lines studied were B16-F10 (murine melanoma) and OSCC (oral squamous cell carcinoma). These cell lines showed different behavior after incubation at different formulation concentrations. For cytotoxicty study on B16-F10 cells, it was observed a strong effect caused by Selol (cell viability reached 52.5% ±8.4). On the other hand, there was no cytotoxic effect on B16-F10 cells (p > 0.05) under magnetic field application. OSCC cell line showed a resistance to treatment with selol and in the absence of AC magnetic field. However, after magnetic field activation the cell viability reached 33.3% (±0.3) indicating a strong hyperthermic effect on OSCC cells. Therefore, it has been confirmed nanocapsules containing selol and magnetic fluid are able to destroy B16-F10 or OSCC neoplastic cells indicating an important weapon for future work in the treatment against cancer.

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29

Zelhof, Bachar. "The use of high field strength magnetic resonance imaging in prostate cancer staging and localisation." Thesis, University of Hull, 2012. http://hydra.hull.ac.uk/resources/hull:6866.

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30

Mili, Manhal. "Metabolomics Investigation of Cancer Cells by High Field NMR." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSEN078.

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La métabolomique a acquis au cours des dernières années une place privilégiée en oncologie et en recherche sur la biologie du cancer. La métabolomique cellulaire offre un grand potentiel pour élargir notre champs de connaissance sur les mécanismes du développement tumoral et sur les aspects fondamentaux de la biologie du cancer. Nous avons utilisé l’approche métabolomique par résonance magnétique nucléaire (RMN) pour caractériser les profils métaboliques de lignées cellulaires de cancer suite à leur exposition à des facteurs influençant leur réponse aux traitements. Premièrement, nous avons développé une méthodologie rigoureuse, rapide et ergonomique d’extraction des métabolites pour l’analyse métabolomique à partir de cultures cellulaires adhérentes mammifères. Par la suite, l’approche métabolomique a été utilisée pour étudier l’effet des adipocytes, constituants du microenvironnement tumoral, sur les exo- et endo-métabolomes des cellules cancéreuses HER2-positif. Il a été auparavant démontré que les adipocytes agissent sur les cellules cancéreuses HER2-positif en co-culture par l’intermédiaire de leurs facteurs sécrétés en induisant une résistance aux thérapies ciblées. L’ajout d’un stimulateur de lipolyse (isoprénaline, agoniste des récepteurs adrénergiques) au système de co-culture induit une résistance aux thérapies ciblées au moins aussi importante qu’en présence d’adipocytes seuls. Au contraire, l’ajout du propranolol (β-bloquant non sélectif) permet de retrouver la sensibilité de cellules cancéreuses aux thérapies ciblées. L’analyse métabolomique permet d’élucider les aspects mécanistiques mises en jeu lors de cette interaction en étudiant ses conséquences sur les profils métaboliques des cellules cancéreuses. L’analyse quantitative des métabolites présents dans les surnageants de culture montre une forte altération du métabolisme des cellules cancéreuses HER2-positif incubées en milieu conditionné d’adipocytes. Les cellules cancéreuses ne dépendent plus de la glycolyse aérobie mais privilégient l’utilisation d’autres carburants tels que le lactate et le glycérol. L’étude pharmaco-métabolomique des adipocytes et des cellules cancéreuses HER2-positif en présence de modulateurs de lipolyse confirme ces résultats et permet d’observer les changements métaboliques au niveau intracellulaire. Un dernier axe de ce travail porte sur l’étude des profils métaboliques des cellules du cancer de côlon suite à la déplétion de la machinerie AIF/CHCHD4. Les déficits du métabolisme mitochondrial oxydatif sont associées à de nombreuses maladies. Bien qu’une discrimination robuste n’ait pu être observée entre les groupes contrôle et déplété CHCHD4, nous avons identifié un nombre de variables confondantes dont le contrôle est nécessaire pour des études avancées sur le métabolisme oxydatif des cellules cancéreuses avec déplétion de CHCHD4
Metabolomics has become an established tool for oncology and cancer biology research studies. Cell metabolomics is a rapidly growing field that addresses fundamental aspects of cancer biology and provides mechanistic insights into disease development, progression and response to therapies. We developed and applied cell metabolomics approaches by liquid nuclear magnetic resonance (NMR) at very high fields to study the effect of different factors on cancer cells metabolic profiles and ultimately their response to therapy. First we developed a fast, rigorous and ergonomic extraction protocol of adherent mammalian cells for NMR-based metabolomics studies. Then we investigated the effect of adipocytes on HER2-positive cancer cells exo- and endometabolomes. Adipocytes were previously shown to act on HER2-positive cells to decrease their sensitivity to targeted therapy in co-culture. Addition of a lipolysis stimulator (isoprenaline, a β-adrenoreceptor agonist) to the system led to resistance of HER2-positive cells to targeted therapy at least as strong as in the case of adipocytes alone. Conversely, addition of a lipolysis inhibitor (non-selective β-blocker propranolol) rescued the response to therapy. Investigation of supernatants of HER2-positive cells cultures exposed to conditioned media from adipocytes showed strong metabolic alterations in cancer cells exometabolomes. Quantitative analysis of HER2-positive cell footprints shows that tumor cells switched their metabolism from aerobic glycolysis to scavenging various metabolites such as lactate and glycerol. A pharmaco-metabolomic investigation of adipocytes and HER2-positive cancer cells co-cultures and associated controls, conducted with or without addition of propranolol and isoprenaline, confirmed the observed metabolic shift. It revealed changes occurring in adipocytes and HER2-positive cancer cells following exposition to lipolysis modulators. Overall, this metabolomics investigation provides new insights into the mechanisms by which pharmacological modulation of lipolysis via β-adrenoreceptors impact on HER2-positive cancer cell metabolism. Finally, we studied the effect of the knockdown of AIF/CHCHD4 import machinery on colon cancer cells. Defects in oxidative energy metabolism is linked to several mitochondrial diseases that remain poorly understood. While no robust discrimination between control and CHCHD4 knockdown groups was observed, we identified a number of confounding factors that may be controlled for further investigation of oxidative energy metabolism in CHCHD4 knocked down cells

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31

Dani, Raj Kumar. "Exploring physical properties of nanoparticles for biomedical applications." Diss., Kansas State University, 2012. http://hdl.handle.net/2097/13773.

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Doctor of Philosophy
Department of Chemistry
Viktor Chikan
The research work in this thesis aims at investigating the basic physic-chemical properties of magnetic and metal nanoparticles (NPs) for biomedical applications such as magnetic hyperthermia and controlled drug release. Magneto-plasmonic properties of magnetic NPs are important to evaluate potential applications of these materials. Magnetic property can be used to control, monitor and deliver the particles using a magnetic field while plasmonic property allows the tracking of the position of the particles, but aggregation of NPs could pose a problem. Here, the aggregation of NPs is investigated via the Faraday rotation of gold coated Fe[subscript]2O[subscript]3 NPs in alternating magnetic fields. In addition, the Faraday rotation of the particles is measured in pulsed magnetic fields, which can generate stronger magnetic fields than traditional inductive heaters used in the previous experiments. In the second project, the formation of protein-NPs complexes is investigated for hyperthermia treatment. The interactions between gold and iron-platinum NPs with octameric mycobacterial porin A from Mycobacterium smegmatis (MspA) and MspA[superscript])cys protein molecules are examined to assemble a stable, geometrically suitable and amphiphilic proteins-NPs complex. Magnetic NPs show promising heating effects in magnetic hyperthermia to eliminate cancer cells selectively in the presence of alternating magnetic field. As a part of investigation, the heating capacity of a variety of magnetic NPs and the effects of solvent viscosity are investigated to obtain insight into the heating mechanism of these particles. Finally, the controlled drug release of magnetic NPs loaded liposomes by pulsed magnetic field is investigated. The preliminary data indicate about 5-10% release of drug after the application of 2 Tesla magnetic pulses. The preliminary experiments will serve as the initial stage of investigation for more effective magnetic hyperthermia treatment with the help of short magnetic pulses.

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32

Kesse, Xavier. "Elaboration de nanoparticules magnétiques et bioactives pour le traitement du cancer et la régénération de tissus osseux." Thesis, Université Clermont Auvergne‎ (2017-2020), 2019. http://www.theses.fr/2019CLFAC066.

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La plupart des patients atteints de cancer développent également des métastases osseuses dues à la migration des cellules tumorales primaires. L’extraction de la masse tumorale par une intervention chirurgicale fait partie des traitements classiques utilisés en milieu clinique, néanmoins elle détériore considérablement la qualité de vie du patient. Dans un tel contexte, il est donc nécessaire d’améliorer cette thérapie afin de minimiser les inconvénients qui y sont associés. Nous proposons l’élaboration d’un biomatériau multifonctionnel, constitué de verre bioactif et de nanoparticules magnétiques en vue de combiner les effets bénéfiques de la régénération osseuse et de la destruction des cellules cancéreuses par hyperthermie magnétique. En effet, après implantation de ces particules dans le défaut osseux généré par l’exérèse de la masse tumorale, la production de chaleur sous champ magnétique alternatif pourrait détruire les cellules cancéreuses restantes ou résurgentes, puis le verre bioactif induirait la minéralisation osseuse dans la cavité. Dans une première partie, l’influence des paramètres de synthèse (voie sol-gel) sur la composition et les propriétés texturales de nanoparticules bioactives (SiO2-CaO) a été étudiée. L’impact de la composition sur leur bioactivité a ensuite été évalué. Dans une deuxième partie, des nanoparticules à structure cœur-coquille composées de maghémite (γ-Fe2O3) et de verre bioactif (SiO2-CaO) ont été synthétisées et caractérisées. Les bonnes performances en termes de pouvoir chauffant (SAR) et de bioactivité des hétérostructures γ-Fe2O3@SiO2-CaO ouvrent la voie pour leur utilisation pour le traitement des tumeurs osseuses
Most patients suffering of cancer develop bone metastases because of the migration of primary tumors cells. Surgical extraction is one of the commonly used therapies in clinical settings but deteriorates significantly the patient quality of life. In this context, it is needed to improve this therapy to minimize its side effects. We propose to design a new kind of multifunctional biomaterial, composed of bioactive glass and iron oxide nanoparticles to combine the benefits of bone regeneration and destruction of cancerous cells through magnetic hyperthermia. Indeed, these particles could be implanted into the cavity originating from the tumor removal, and the heat produced by the magnetic particles in an alternative magnetic field would destroy selectively the remaining or resurgent cancerous cells. Finally, the bioactive glass would induce the bone regeneration in the cavity. In a first part of this work, the influence of the synthesis parameters (sol-gel process) on the composition and the textural properties of bioactive nanoparticles (SiO2-CaO) have been studied. The impact of their composition on their bioactivity has then been investigated. In a second part, core/shell nanoparticles composed of maghemite (γ-Fe2O3) and bioactive glass (SiO2-CaO) have been synthesized and characterized. The good performances in terms of heating power (SAR) and bioactivity of the γ-Fe2O3@SiO2-CaO heterostructures pave the way to their use for bone cancer treatment

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Fages, Anne. "High-field NMR Metabonomics for Investigation of Cancer in Human Populations and Metabolic Perturbations in Model Systems." Thesis, Lyon, École normale supérieure, 2013. http://www.theses.fr/2013ENSL0876.

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La métabonomique est une approche de choix pour l’identification de biomarqueurs d’intérêts pour le diagnostic de pathologies mais aussi pour l’amélioration de notre compréhension des processus physiopathologiques. La métabonomique offre de nouvelles perspectives en épidémiologie moléculaire, objet principale de cette thèse. Nous avons appliqué l’approche métabonomique par RMN à haut champ à l’analyse de sérums sanguins issus de la cohorte prospective EPIC (European Prospective Investigation into Cancer and nutrition) dans le but d’identifier des biomarqueurs de la survenue du cancer du foie et du cancer du pancréas. L’analyse statistique des profiles métaboliques des sérums obtenus par RMN à 800MHz a permis de mettre en évidence une signature métabolique associée à l’occurrence des hépatocarcinomes (HCC) à cinq ans avant diagnostic en moyenne. L’analyse stratifiée des données a révélé des biomarqueurs précoces mais aussi des biomarqueurs de l’étiologie des HCC. L’analyse métabonomique portée sur le cancer du pancréas n’a à l’inverse pas été concluante. Des méthodes pertinentes pour l’analyse des cohortes épidémiologiques par métabonomique ont été développées, telle qu’une méthode de correction d’effet batch rendant possible la comparaison de données RMN acquises au cours d’une longue période de temps. La méthode statistique PCPR2 développée permet de quantifier l’impact de différents facteurs sur les données métabonomique afin d’en révéler les sources de variations systématiques. D’autre part, l’approche métabonomique permet également l’investigation de questions biologiques plus fondamentales. Cette thèse offre une approche de génomique fonctionnelle à l’étude des cibles métaboliques du récepteur aux hormones thyroïdiennes TRβ dans le foie. L’analyse des données HR-MAS de tissus de foie intacts complémentée par l’analyse d’extraits hépatiques sur un modèle de souris a permis d’éclaircir le rôle de ce récepteur nucléaire
Metabonomics is a recent approach that enables not only to identify relevant biomarkers for disease diagnosis but also to improve our understanding of biological processes by gaining insight into metabolism. This thesis is mainly dedicated to the application of metabonomics to molecular epidemiology. High-field NMR metabonomic approach was applied to the analysis of serum samples from the large prospective cohort EPIC (European Prospective Investigation into Cancer and nutrition) to identify biomarkers of liver cancer and pancreatic cancer occurrence. The statistical analysis of NMR serum metabolic profiles obtained at 800 MHz enabled to highlight a metabolic signature associated with the occurrence of hepatocellular carcinoma (HCC), in average five years before diagnosis. The stratified analysis revealed both early and etiologic biomarkers of HCC. The NMR metabonomic analysis of the pancreatic cancer did not reveal any metabolic signature of this cancer. Moreover, relevant methods to allow the NMR metabonomic analysis of epidemiological cohort were developed. This thesis proposes a method to correct data for batch effect, making possible the comparison of NMR data recorded in a long period of time. The statistical method PC-PR2 developed enables the quantification of the contribution of different factors onto metabonomic data to reveal systematic variation sources. In addition, the metabonomic approach is also suitable to address specific biological questions by providing a new read-out of the metabolism. Functional genomics by NMR metabonomics was used in this thesis to study the metabolic targets of the thyroid hormone nuclear receptor TRβ in the liver. The analysis of HR-MAS data obtained on intact liver tissue in addition to the analysis of NMR data of liver extracts from a mice model enabled to better understand the role of this nuclear receptor

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Branquinho, Luis Cesar. "Efeito da interação dipolar magnética na eficiência de aquecimento de nanopartículas: Implicações para magnetohipertermia." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/7239.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Magnetic nanoparticles can generate heat when submitted to alternating magnetic fields of adequate amplitude and frequency. This phenomenon is named magnetic hyperthermia and has several therapeutic applications, as for example, in the treatment of cancer. In general, the theoretical models used to describe this neglect the effect of interparticle interaction. In this thesis we investigate the effect of magnetic dipolar interaction in the magnetothermal efficiency (named specific loss power – SLP) of bicompatible magnetic nanoparticles. Firstly, we develop a chain of magnetic particles model, where we prove that the interaction leads to a contribution to the uniaxial anisotropy. This term in the free energy density allowed us to extract from the electron magnetic resonance technique (EMR) information about the mean chain size in the colloid. Further, this additional magnetic nanoparticle anisotropy term was used to develop an analytical theoretical model that takes into account the effect of the dipolar interaction between nanoparticles to SLP, considering the case where the magnetization responds linearly to the field (Linear Response Theory). Our calculations indicate that depending on the particle parameters, specially the anisotropy, the effect can be to enhance or decrease the heat generation. Moreover, we showed that increasing the chain size (number of particles in the chain) the optimal particle size for hyperthermia can decrease up to 30% in comparison with non-interacting particles. This result has several clinical implications, which allowed us to suggest some strategies for improving the therapeutic efficacy. In order to investigate experimentally the effect, two magnetic fluids, one containing spherical nanoparticles based on manganese ferrite (MnF-citrate) in the superparamagnetic regime, and another commercial one (BNF-starch) magnetite-based with a shape of a parallellepiped and blocked, were selected and deeply characterized. We found a decrease of SLP increasing the chain size for the MnF sample, while for BNF-starch no effect was found at the same experimental conditions. The decrease of SLP in the MnF sample, within the particle concentration range, was explained considering in the model not only the effect in the anisotropy but also by an increase in the damping factor parameter, a term correlated to spin-phonon interaction. Data obtained using EMR and Monte Carlo simulations corroborate our hypothesis. The absence of concentration effect for the BNF sample was attributed to the higher anisotropy value and to the probable influence of brownian relaxation. In addition, the same chain model was used to investigate the behavior of blocked nanoparticles of Stoner-Wohlfarth type. In this case, we demonstrate that the chain formation increases the magnetic hyperthermia, as found in magnetosomes. Finally, we showed that a fluctuation of the dipolar interaction field between particles in the chain, which does not destroy the symmetry of this term, shows a Vogel-Fulcher behaviour in the weak coupling regime.
Nanopartículas magnéticas são capazes de gerar calor quando submetidas a campo magnético alternado de amplitude e frequência adequadas. Este fenômeno é conhecido como magnetohipertermia e possui aplicações terapêuticas como, por exemplo, no tratamento de câncer. Em geral, os modelos teóricos que descrevem o fenômeno não levam em conta efeitos associados à interação partícula-partícula. Nesta tese investigamos o efeito da interação dipolar magnética na eficiência magnetotérmica (SLP) de nanopartículas magnéticas biocompatíveis. Primeiramente desenvolvemos um modelo de cadeia de nanopartículas magnéticas, aonde provamos que a interação entre partículas que formam uma cadeia linear equivalem a uma contribuição uniaxial a anisotropia. Essa contribuição à densidade de energia permitiu que obtivéssemos por meio da técnica de ressonância magnética eletrônica (RME) informações acerca do tamanho médio de aglomerado na suspensão coloidal. Posteriormente utilizamos esse termo adicional da anisotropia efetiva da nanopartícula para propor um modelo teórico analítico que leve em consideração o efeito de tal interação na eficiência de aquecimento de nanopartículas magnéticas em um fluido para o caso em que a magnetização das nanopartículas responde linearmente ao campo (Teoria da Resposta Linear). Nossos cálculos indicaram que, dependendo de parâmetros da nanopartícula, em particular da anisotropia, este efeito pode aumentar ou diminuir a geração de calor. Além disso, mostramos que o aumento do número de partículas formando cadeias lineares reduz o diâmetro ótimo para hipertermia em até 30% em relação ao valor esperado para partículas isoladas. Este resultado possui fortes implicações clínicas, e permitiu que sugeríssemos algumas estratégias para aumentar a eficiência terapêutica. No intuito de investigar experimentalmente este efeito, dois fluidos magnéticos, um contendo nanopartículas esféricas de ferrita de Mn (MnF-citrato) no regime superparamagnético e outra comercial (BNF-starch) à base de magnetita com forma de nanoparalelepípedos e contendo partículas bloqueadas, foram selecionados e amplamente caracterizados. Observamos uma diminuição no SLP com o aumento de partículas na cadeia para a amostra MnF-citrato, para todos os valores de campo, enquanto que para a amostra BNF-starch não percebemos alteração do SLP. O decréscimo do SLP da amostra MnF, na faixa de concentração investigada, foi explicado incluindo não apenas o efeito na anisotropia efetiva, mas também o aumento no valor do fator de amortecimento. Dados de RME e simulação de Monte Carlo corroboraram tal hipótese. A ausência de efeito para amostra BNF-starch foi atribuída à alta anisotropia e provável influência de relaxação browniana. Adicionalmente, o modelo de cadeia foi usado para explicar o comportamento de nanopartículas bloqueadas do tipo Stoner-Wohlfarth. Neste caso demonstramos que a formação de cadeias aumenta a hipertermia magnética, como verificado em magnetossomos. Finalmente, mostramos que uma flutuação no campo dipolar interpartículas na cadeia, que não destrua a simetria desta contribuição, fornece um comportamento do tipo Vogel-Fulcher no regime fracamente interagente.

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Perecin, Caio José. "Nanopartículas superparamagnéticas encapsuladas com polímeros para tratamento de câncer por hipertermia." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/82/82131/tde-22062016-103823/.

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O câncer é uma das maiores causas de mortalidade no Brasil e no mundo, com potencial de crescimento nas próximas décadas. Um tipo de tratamento promissor é a hipertermia magnética, procedimento no qual as células tumorais morrem pelo efeito do calor gerado por partículas magnéticas após a aplicação de campo magnético alternado em frequências adequadas. Tais partículas também são capazes de atuar como agentes de contraste para imageamento por ressonância magnética, um poderoso método de diagnóstico para identificação de células neoplásicas, formando a combinação conhecida como theranostics (terapia e diagnóstico). Neste trabalho foram sintetizadas nanopartículas de óxido de ferro por método de coprecipitação com posterior encapsulação por técnica de nano spray drying, visando sua aplicação no tratamento de câncer por hipertermia e como agente de contraste para imageamento por ressonância magnética. Para a encapsulação foram utilizadas matrizes poliméricas de Maltodextrina com Polissorbato 80, Pluronic F68, Eudragit® S100 e PCL com Pluronic F68, escolhidos com o intuito de formar partículas que dispersem bem em meio aquoso e que consigam atingir alvo tumoral após administração no corpo do paciente. Parâmetros de secagem pelo equipamento Nano Spray Dryer, como temperatura, solvente e concentração de reagentes, foram avaliados. As partículas formadas foram caracterizadas por Microscopia Eletrônica de Varredura, Difração de Raios-X, Análise Termogravimétrica, Espalhamento de Luz Dinâmico, Espectroscopia de Infravermelho, magnetismo quanto a magnetização de saturação e temperatura, citotoxicidade e potencial de aquecimento. Tais procedimentos indicaram que o método de coprecipitação produziu nanopartículas de magnetita de tamanho em torno 20 nm, superparamagnéticas a temperatura ambiente, sem potencial citotóxico. A técnica de nano spray drying foi eficiente para a formação de partículas com tamanho em torno de 1 μm, também superparamagnéticas, biocompatíveis e com propriedades magnéticas adequadas e para aplicações pretendidas. Destaca-se a amostra com Pluronic, OF-10/15-1P, que apresentou magnetização de saturação de 68,7 emu/g e interação específica com células tumorais.
Cancer is one of the greatest causes of mortality in Brazil and in the world, with growing potential for the next decades. A promising treatment alternative is magnetic hyperthermia, in which tumor cells die by the heat generated by magnetic nanoparticles after application of an alternate magnetic field in adequate frequencies. Such particles are also capable of acting as contrast agents for magnetic resonance imaging, a powerful method of diagnosis for the identification of neoplasic cells, which characterizes the combination of properties known as theranostics (therapy and diagnosis). In this work, iron oxide nanoparticles were synthesized by coprecipitation method with subsequent encapsulation by nano spray drying technique, aiming their application on cancer treatment by hyperthermia and on magnetic resonance imaging as a contrast agent. Polymeric matrices of Maltodextrin with Polysorbate 80, Pluronic F68, Eudragit® S100 and PCL with Pluronic F68 were employed for encapsulation, chosen carefully to create particles that disperse well in aqueous media and that are able to address the tumoral target after administration into the patient\'s body. Drying parameters of the Nano Spray Dryer equipment, such as temperature, dispersing medium and reagent concentrations, were evaluated. The generated particles were characterized by Scanning Electron Microscopy, X-Ray Diffraction, Thermogravimetric Analysis, Dynamic Light Scattering, Infrared Spectroscopy, by magnetism in matters of applied magnetic field and temperature, cytotoxic potential and heating potential. Such methods indicated that the coprecipitation method was able to produce magnetite nanoparticles with size of approximately 20 nm, superparamagnetic at room temperature and with no cytotoxic potential. The nano spray drying technique was efficient to produce particles with size of around 1 μm, biocompatible, superparamagnetic and with adequate magnetic properties for the intended applications. The sample OF-10/15-1P stands out with a saturation magnetization of 68.7 emu/g and presenting specific interactions with the tumour cells.

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Marie, Hélène. "Magnétoliposomes pour le diagnostic et le traitement du glioblastome par vectorisation magnétique et hyperthermie." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114834.

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L’ensemble de l’étude in vivo réalisée sur souris porteuses de glioblastome U87 démontre la faisabilité du ciblage magnétique pour accumuler les magnétoliposomes superparamagnétiques, ou MFLs, au niveau du glioblastome, tout en préservant le reste du tissu cérébral sain. L’étude révèle que le bénéfice apporté par l’action d’un gradient de champ magnétique produit par un aimant extracorporel repose sur un effet EPR (« enhanced permeation and retention » effect) amplifié. Les résultats sont étayés par la combinaison de plusieurs techniques (IRM, RPE, microscopie confocale de fluorescence, microscopie électronique). Concernant les mécanismes de transport empruntés par les magnétoliposomes pour atteindre les cellules tumorales, la voie d’endocytose non spécifique s’apparentant à un processus de macropinocytose est pressentie. Dans l’optique d’une application thérapeutique par hyperthermie, la capacité d’échauffement des magnétoliposomes a été pour la première fois explorée. Les résultats prouvent un comportement thermique des magnétoliposomes compatible avec les conditions d’un traitement par hyperthermie. Enfin, dans le cadre d’une étude portant sur le développement de cancers mécano-induits, l’application des magnétoliposomes a été élargie un autre organe non étudié à ce jour, le côlon. Ces travaux illustrent la problématique de la vectorisation magnétique au sein d’un organe situé dans une région interne de l’organisme
First, the in vivo study on U87-glioblastoma bearing mice demonstrates the ability of magnetic targeting to accumulate magnetic-fluid-loaded liposomes (MFLs) into glioblastoma while sparing the rest of the healthy brain tissue. The enhancement of liposome local concentration by applying a magnetic field gradient produced by an external magnet is based on an amplified EPR effect (“enhanced permeation and retention” effect). The results were supported by combining several techniques (MRI, ESR, confocal fluorescence microscopy, electron microscopy). The investigations concerning the mechanisms of transport of the magnetoliposomes to reach the tumor cells suggest a non-specific endocytose pathway, presumably macropinocytosis. Secondly, in the context of a therapeutic application by hyperthermia the heat capacity of MFLs was explored. The results showed that the thermal behaviour of the magnetoliposomes depends on the containment state of the iron oxide nanocrystals and is compatible with the conditions of hyperthermia treatment. Finally, as part of a study concerning the development of mechanically induced cancers, application of MFLs was extended to target another organ not yet studied: the colon. This work especially illustrates the potential and related limits of magnetic targeting towards an organ located in an inner region of the body

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Wu, Xia. "Determination of DNA replication program changes between cancer and normal cells by sequencing of Okazaki fragments." Thesis, Paris Sciences et Lettres (ComUE), 2016. http://www.theses.fr/2016PSLEE032.

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Jusqu'à présent, les modifications de la réplication de l'ADN entre cellules normales et cancéreuses ont été peu étudiées. Dans ce travail, nous avons utilisé le séquençage des fragments d'Okazaki, une technique récemment développée au laboratoire, pour déterminer la directionalité des fourches de réplication dans plusieurs lymphomes de Burkitt (LB), qui surexpriment l'oncoprotéine Myc à la suite de translocations chromosomiques spécifiques, ainsi que dans des lignées lymphoblastoides contrôles (LLC) et dans des léiomyosarcomes (LMS). Les profils de directionalité des fourches de réplication permettent de déduire la localisation et l'efficacité des sites d'initiation et de terminaison de la réplication le long du génome. Nous avons observé de nombreuses (~2000) différences de zones d'initiation entre les lignées Raji (LB) et GM06990 (LLC) ainsi qu'entre les lignées BL 79 et IARC385, une paire LB/LLC provenant d'un même patient. Nous avons détecté un nombre comparable de différences en comparant deux à deux les lignées étudiées. Cependant, les profils de BL79 et de Raji (deux LB) sont un peu plus proches l'un de l'autre que de la lignée contrôle GM06990. Ceci suggère l'existence de changements de la réplication récurrents dans les lignées LB. L'importance des différences observées entre les lignées IARC385 et GM06990 indique de façon surprenante une grande variabilité entre les LLC normales, provenant de différents individus. De façon intéressante, de nombreuses différences observées entre les lignées LB et LLC sont associées à des changements de l'expression des gènes ou de la liaison de l'oncoprotéine Myc. La comparaison des profils des deux LMS avec tous les profils disponibles au laboratoire montre que c'est à celui de fibroblastes normaux (IMR90) qu'ils ressemblent le plus. Ceci suggère que les cellules de tumeurs musculaires lisses auraient subi une transformation fibroblastique au cours de la tumorigénèse. Des données récentes suggèrent que les champs magnétiques peuvent perturber certains processus cellulaires comme l'assemblage du cytosquelette. Nous avons utilisé le séquençage de fragment d'Okazaki pour rechercher d'éventuels effets d'un champ magnétique sur la réplication de l'ADN chez la levure. Aucun effet du champ magnétique sur la directionalité des fourches de réplication n'a été détecté
Changes in DNA replication profiles between cancer and normal cells have been poorly explored. In this work, sequencing of Okazaki fragments, a novel methodology developed in the laboratory, was used to determine replication fork directionality (RFD) in several Burkitt's lymphomas (BL), which overexpress the Myc oncoprotein due to specific chromosomal translocations, and control normal lymphoblastoid cell lines (LCL), and in leiomyosarcomas (LMC). RFD profiles allow to infer the location and efficiency of replication initiation and termination sites genome-wide. A larger number (~2000) of differences in replication initiation zones were observed genome-wide between Raji (BL) and GM06990 (LCL), and between BL79 and IAR385, a BL / LCL pair of cell lines established from a single patient. Comparably large numbers of changes were slightly more similar to each other than to GM06990. This suggests the occurrence of some recurrent replication changes in BL cell lines. The large number of changes observed between IARC385 and GM06990 also indicates an unexpectedly large variation between normal LCLs of different individuals. Interestingly, many changes in RFD profiles between BLs and and LCLs are associated with cell-type specific gene expression and differential binding of the Myc oncoprotein. Comparison of the two LMS profiles with all RFD profiles available in the laboratory reveals that they most resemble normal fibroblasts (IMR90). This suggests that the smooth muscle cancer cells might have undergone a fibroblastic transformation during tumorigenesis. Magnetic fields have been reported to perturb cellular processes such as cytoskeleton assembly. Sequencing of Okazaki fragments was used in a preliminary investigation of the possible effects of magnetic fields on DNA replication in yeast cells. No effect of magnetic fields on replication fork directionality were observed

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Paudel, Liladhar. "High Field ¹H Nuclear Magnetic Resonance (NMR) Spectroscopy Based Metabolomics and Complex Mixture Analysis by Multidimensional NMR and Liquid Chromatography-Mass Spectrometry (LC-MS)." University of Akron / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=akron1343403647.

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Jeanjean, Pauline. "Thermothérapies guidées par imagerie pour le traitement des cancers." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0396.

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Ce travail de thèse prouve que la combinaison de la thermoablation et de l’hyperthermie modérée peut être utilisée pour le traitement des tumeurs solides. La preuve de concept a été établie par imagerie moléculaire in vitro sur des cellules en culture et in vivo sur des modèles murins.La viabilité des cellules cancéreuses en culture et au sein des tumeurs implantées a été suivie par imagerie de bioluminescence grâce à l’expression constitutive de luciférases. De la même manière, l’utilisation d’un promoteur thermo-inductible couplé à un gène rapporteur d’imagerie a permis d’identifier les zones d’hyperthermie modérée. L’élévation de la température a été réalisée de manière non invasive par hyperthermie magnétique et ultrasons focalisés guidés par IRM. L’hyperthermie magnétique a été effectuée à l’aide de nanoparticules magnétiques d’oxyde de fer placées dans un champ magnétique alternatif et l’élévation de température a été monitorée par imagerie infrarouge. La distribution des nanoparticules magnétiques a été suivie par microscopie photonique et électronique, cytométrie en flux et imagerie de fluorescence. Les ultrasons focalisés ont également été utilisés pour le chauffage des tumeurs. Les variations de températures ont été mesurées par IRM et l’information de température a été utilisée pour contrôler en temps réel la puissance des ultrasons. Ces approches expérimentales in vivo ont permis de démontrer qu’une thermoablation tumorale centrale peut être combinée à une hyperthermie modérée périphérique du microenvironnement tumoral.Parce que l’hyperthermie magnétique et les ultrasons focalisés guidés par IRM sont actuellement en clinique, nos résultats ouvrent des perspectives de thérapie anticancéreuse en associant à la thermoablation des stratégies de thérapies innovantes basées sur la libération contrôlée de médicament encapsulé dans des nanoparticules thermosensibles ou l’expression thermo-inductible de gènes thérapeutiques
This present work demonstrates that thermal ablation and mild hyperthermia could be combined for solid tumor treatment. Proof of concept was established by molecular imaging in cell culture in vitro and using mouse models in vivo.Cancer cell viability in culture and in the tumor was followed by bioluminescence imaging using luciferases constitutive expression. Imaging reporter genes were also coupled with thermo-induced promoter to visualize mild hyperthermia areas in mice. The temperature rise was achieved using non-invasive techniques such as magnetic hyperthermia and MR-guided focused ultrasounds. Magnetic hyperthermia was performed using iron oxide magnetic nanoparticles placed in an alternative magnetic field to induce an increase of temperature monitored by infrared imaging. Magnetic nanoparticles distribution was followed by photonic and electronic microscopy, flow cytometry and fluorescence imaging. Focused ultrasounds have also been used for tumor heating. Temperature changes were followed by MR and temperature used to control in real time the ultrasonic power. These in vivo experimental approaches demonstrated that central tumor thermal ablation could be combined with peripheric mild hyperthermia of tumor microenvironment.As magnetic hyperthermia and MR-guided focused ultrasounds are currently in clinic, our results reveal new opportunities for cancer therapies combining thermal ablation with innovative strategies based on controlled drug release from thermo-sensitive nanoparticles or thermo-induced therapeutic gene expression

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Vurro, Federica. "Characterization and optimization of nano-structures with hyperthermic properties for biomedical applications." Doctoral thesis, 2020. http://hdl.handle.net/11562/1018385.

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In the last years, our group focused on magnetic nanoparticles (MNPs), which are able to induce hyperthermia, as potential biomedical tools. Magnetic hyperthermia is a term used to denote the generation of heat by MNPs in response to the application of an external alternating magnetic field. We applied hyperthermia in vitro with different aims and the effects on cells were analyzed by applying viability test and morphological analysis with light and transmission electron microscopy (TEM) techniques. We used superparamagnetic iron oxide nanoparticles (NPs) to induce delipidation in 3T3L1 adipocytes and human adipose-derived adult stem cells. Immediately after hyperthermia, we observed a drastic intracellular lipid loss that persisted for at least 24h in the absence of cell death, damage or dedifferentiation. These results open interesting perspectives for the application of hyperthermia to treat obesity. We applied hyperthermic treatment also to cancer cells, known to be more sensitive to heat shock than healthy cells, in order to induce apoptosis. A glioblastoma cell line (U87MG) was treated with either Zn-SPIONs or biomimetic magnetic NPs (BMNPs). Zn-SPIONs are amphiphilic polymer, dodecyl grafted poly(isobutylene-alt-maleic anhydride) coated zinc-doped iron oxide (Fe3O4) NPs of 15±2 nm size, and show a high thermal capacity. BMNPs, synthetized with the protein MamC from magnetotactic bacteria, may act as both drug carriers and hyperthermic agents, being promising tools for the treatment of many types of tumor. BMNPs were also tested in a human hepatocyte carcinoma cell line (HepG2) after functionalizaton with a Choline Kinase inhibitor in order to obtain a nanocarrier potentially suitable for targeted chemotherapy. In fact, Choline Kinase is considered as a biomarker of tumor progression and carcinogenesis, and a target therapy. Therefore, our nanocarriers would allow a local treatment of cancer thus avoiding/reducing possible systemic side effects. The internalization of BMNPs was evaluated using TEM. Taken together, our results prove the efficacy of MNPs in inducing hyperthermia in cultured cells. Although these basic data have been obtained in in vitro models, they suggest the suitability of these NPs as therapeutic tools and encourage further studies for their application in the biomedical field.

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41

Mohite, Virendra Haik Yousef. "Self controlled magnetic hyperthermia." 2004. http://etd.lib.fsu.edu/theses/available/etd-11152004-184909.

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Thesis (M.S.)--Florida State University, 2004.
Advisor: Dr. Yousef S. Haik, Florida State University, College of Engineering, Dept. of Mechanical Engineering. Title and description from dissertation home page (Jan. 13, 2005). Includes bibliographical references.

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42

"Engineering magnetic viral nanoheaters for targeted hyperthermia treatment of cancer." Thesis, 2009. http://hdl.handle.net/1911/61895.

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Extensive investigations into the multifunctional nature of magnetic nanoparticles have sparked a burgeoning interest in their use for biomedical applications. The potential of abolishing cancer via externally induced hyperthermia has inspired the development of a plethora of systems used to deliver superparamagnetic compounds to cancerous cells while avoiding non-target tissue. The prevailing challenges are: (A) generating particles capable of selectively binding and entering oncolytic targets to generate internal heating and (B) delivering adequate amounts of magnetic particles that generate sufficient heat at clinically acceptable field levels. Adeno-associated virus (AAV) has yet to be exploited as a hyperthermia agent but lends itself well to manipulation as a superparamagnetic nanoparticle since it is genetically encoded and can be precisely engineered to concomitantly meet multiple aims. Specific aims of the project were: (1) endow AAV with superparamagnetic potential through genetic engineering, and (2) target virus-metal nanoparticles to cancer cells through laboratory directed evolution.

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43

Hsu, Tung-Jung, and 許彤蓉. "PEG-FA Conjugated Magnetic Gelatin/CaP for Lung Cancer Hyperthermia." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/m5tz2m.

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碩士
國立臺北科技大學
材料科學與工程研究所
99
Dicalcium phosphate dehydrate ( DCPD ) is the major component of hard tissues like bone and teeth, which is non-toxic, biocompatibility and biodegradable. In this study, the Fe-DCPD particles was formed by co-precipitation method. The iron ions can substitute calcium ions of DCPD and form a magnetic DCPD；by doing this it can release heat in alternating magnetic field because it has magnetism. As temperature rise up to 43~46℃, the heat treatment will cause cancer cells dead. However, in order to extend the blood circulation time and improve the targeting rate, the surface modification is necessary. Therefore, gelatin was used as a mediator to immobilize polyethylene glycol (PEG) and folic acid (FA) on the magnetic particle surface. It is believed that magnetic Fe-DCPD/Gelatin-PEG-FA is one of the most potential materials in lung cancer hyperthermia by using in halation in the future.

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44

Hsieh, Shun-Yu, and 謝舜祐. "Hyaluronic Acid Modified Magnetic Hydroxyapatite Nanocrystals for Targeted Hyperthermia Cancer Therapy." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/83274043369182515089.

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45

Ta-ChunLin and 林大鈞. "Electrospun Chitosan Nanofibers Containing Magnetic Nanoparticles for Hyperthermia in Cancer Therapy." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/18032493858887282075.

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博士
國立成功大學
化學工程學系碩博士班
101
Hyperthermia has been reported as one of the effective cancer treatment modalities since the tumor cells are more temperature sensitive than their normal counterparts. Magnetic nanoparticles were the thermoseeds under an alternating magnetic field and can be used to produce highly localized hyperthermia effect on deep-seated tumor. Nevertheless, effective and precisive delivery of nanoparticles to the treatment-intended site remains a challenge. In this study, Fe3O4 nanoparticles were incorporated onto the crosslinked electrospun chitosan nanofibers using chemical co-precipitation from the Fe ions adsorbed. Such magnetic nanoparticle nanofiber composites could be delivered to the treatment site precisely by surgical or endoscopic method. In this preliminary investigation we have explored various characteristics of the biodegradable electrospun chitosan nanofibers containing magnetic nanoparticles that were prepared by different methods. These methods including (1) E-CHS-Fe3O4: the electrospun chitosan nanofibers immersed directly into magnetic nanoparticle solution; (2) E-CHS-Fe2+: the electrospun chitosan nanofibers immersed into Fe+2/Fe+3 solution initially then followed by chemical co-precipitation for magnetic nanoparticles. Iminodiacetic acid (IDA) functionality was grafted onto the chitosan with an aim to increase the amount of magnetic nanoparticles formed in the electrospun magnetic nanofiber composite. The morphology, crystalline phase as well as the magnetism characteristic of the magnetic electrospun nanofiber matrixes was analyzed. The heating properties of these magnetic electrospun nanofibers matrixes under an alternating magnetic field (AMF) were investigated under a frequency of 750 kHz and magnetic intensity of 0.8T. In vitro cell incubation experiments indicated that these magnetic electrospun nanofibers matrixes can effectively reduced the tumor cell proliferation under the application of magnetic field. This finding suggested the magnetic electrospun chitosan nanofiber composite can be of potential for hyperthermia treatment.

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46

Yeh, Mei-Chun, and 葉美君. "To synthetize dual function Pt-Fe-HAP magnetic particles for cancer hyperthermia." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/dvr8aq.

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碩士
國立臺北科技大學
材料及資源工程系研究所
100
Until 2011, cancer already is the top among the ten leading causes death over 28 years in Taiwan. The mortality from cancer is increasing every year. At Biomedicine field that focus on cancer therapies. Reducing side effects, decreasing pain and using effective therapies are the way that we hope for. “Thermotherapy” is the most popular one on cancer therapy. Synthesized with Fe2+ and Pt2+ and used Ca10(PO4)6(OH)2 to replace the Ca2+. By this way to let it got magnetic and have the same effect of Cisplatin. And then we got a Ca10(PO4)6(OH)2 that have composited effective. The preparation for Ca10(PO4)6(OH)2 used Co-precipitation. During operated Co-precipitation that we add FeCl2．4H2O and K2PtCl4 to change compose of Ca10(PO4)6(OH)2 . Keeping temperature at 80 °C, and pH＝9~9.5. And then used Fourier transform infrared rays spectrometer(FTIR) and X-ray diffraction(XRD) those two machine analyzed its’ composite and characteristic. Scanning electron microscopy (SEM), Energy dispersive spectrometer, and Inductively coupled plasma-optical emission spectrometer (ICP-OES) can helps us analyzed its’ surface and chemical property. Finally used Vibrating sample magnetometer (VSM) analyzed its’ magnetic characteristic. Researching result show that it can prepare Ca10(PO4)6(OH)2 by using Co-precipitation. And the content of platinum is 0.034, and iron is 0.133. From the cart of Hystersis curve, it can prove the Ca10(PO4)6(OH)2 has magnetic. Commercial high frequency machine offered alternating current to find our magnetic. And then we can know the thermal energy from magnetic hysteresis. During 10 minutes can get the perfect temperature is 43~46°C.

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47

張富翔. "System Integration and Application of Liver Cancer Treatment for Magnetic Fluid Hyperthermia." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/20470590740218558703.

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48

Wang, Chin-Wen, and 王慶文. "The Fabrication and Characterization of Magnetic Hydroxyapatite as Thermoseed for Cancer Hyperthermia." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/sd5e8q.

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碩士
國立臺北科技大學
材料科學與工程研究所
95
In human body and cells, iron and zinc are very vital elements. High concentration of iron and zinc ions are distributed over the blood, muscle, and the circulatory system. Iron-based and zinc-based compounds can combine with hydroxyapatite and form composites which can presents magnetism. This kind of iron-zinc-containing hydroxyapatite have the potential in Tumor Hyperthermia Application which is the most popular subject in research. In this research, we use the co-precipitation method to synthesize hydroxyapatite. Adding zinc chloride and ferrous chloride with different concentration can modify its atomic structure. Powder composites are prepared at pH = 9 ~ 9.5 and temperature at 80, and then ℃we can obtain its magnetic properties with hysteresis curve analysis. In this study, when we impose a AC - induction magnetic field on our samples, their temperature rise because of hysteresis loss. With In-vitro test, we know that it also has good bio-compatibility and high potential for Tumor Hyperthermia in the future.

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49

Silva, Pedro Manuel Lima da. "Bionanostructures for intracellular temperature sensing during hyperthermia cancer treatments." Master's thesis, 2018. http://hdl.handle.net/1822/65127.

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Dissertação de mestrado em Biophysics and Bionanosystems
Cancer is a disease characterized by abnormal fast growth of cells. The current treatments used, chemo and radiotherapy, besides not being 100 % effective, have also serious side-effects. One of the most promising treatments under study are the hyperthermia ones, where a temperature increase is locally applied. One of such thermal treatments is magnetic hyperthermia, which is performed by local administration of magnetic nanoparticles and their exposure to an alternating magnetic field. This work aims at providing a method to assess the intracellular temperatures achieved during magnetic hyperthermia treatments. The green fluorescence protein (GFP), that is compatible with live cells was used as a luminescent nanothermometer and can report temperature changes from various locations within the cell. Three different GFP variants were analyzed: i) nontagged-GFP was used to test temperature evolution in the cytoplasm, ii) Actin-GFP to test temperature along cytoskeleton proteins and iii) Mito GFP to test the local temperature at the mitochondria. To assure nanothermal sensing during efficient magnetic hyperthermia treatment in in vitro live cell models, first the uptake of magnetic nanoparticles, their intracellular localization and toxicity were analyzed. Inductively couple plasma - optical emission spectroscopy (ICP-OES) results show that Fe3O4 nanoparticles are taken up in a concentration and time-dependent manner. A concentration dependent toxicity is observed at incubation times of 24h, with cell viability decreasing to values lower than 80 %, at concentrations higher than 50 μg/mL. Transmission electron microscopy (TEM) images reveal that such nanoparticles localize mainly in aggregates in vicinities of the nucleus membrane. Temperature dependent studies showed a linear decrease of the GFP fluorescence lifetime with increasing temperature, while no correlation was observable with fluorescence polarization anisotropy when in actin-GFP proteins and in nontagged-GFP. Intracellular temperatures achieved during magnetic hyperthermia treatment using exposure times as reported for clinical tests, approximately 30 min, reach up to 75 ºC degrees, which is considerably higher than required for the induction of local cell death. In summary, a novel intracellular temperature measurement technique based on the fluorescence lifetime measurement of GFP was developed and validated within a range of magnetic nanoparticle concentration that is not considered toxic.
O cancro é uma doença caracterizada por uma divisão celular anormalmente rápida. Os tratamentos convencionais usados (ex: quimio e radioterapia), além de não serem 100 % eficazes, possuem também sérios efeitos secundários. Atualmente os tratamentos hipertérmicos, são muito promissores, onde temperaturas acima do ideal são localmente aplicadas. A hipertermia magnética é um tipo de tratamento hipertérmico que consiste na administração local de nanopartículas magnéticas que são expostas a um campo magnético alternado. Este trabalho teve como objetivo providenciar um método para detetar as temperaturas intracelulares atingidas durante este tipo de tratamento. A proteína verde fluorescente (GFP) foi testada como um nanotermómetro luminescente, para reportar diferenças de temperatura em vários locais intracelulares, uma vez que é compatível com células vivas. Foram analisadas três variantes de GFP: i) GFP não marcada para testar a evolução da temperatura no citoplasma, ii) actina-GFP para testar a temperatura no citoesqueleto, iii) mito-GFP para testar a temperatura na mitocôndria. Para assegurar uma deteção eficiente das temperaturas atingidas durante a hipertermia magnética em modelos in vitro, foi analisado a internalização, localização intracelular e toxicidade das nanopartículas magnéticas. Os resultados de espectrometria de Emissão Ótica por Plasma Acoplado Indutivamente (ICP-ES) mostraram que nanopartículas de Fe3O4 foram internalizadas numa forma dependente do tempo e da concentração. Foi também observado que para tempos de incubação de 24 h, a toxicidade era dependente da concentração, apresentando uma viabilidade celular menor que 80 % para concentrações superiores a 50 μg/mL. Imagens de microscopia eletrónica de transmissão revelaram que estas nanopartículas se encontravam localizadas maioritariamente em agregados nas vizinhanças do núcleo. Estudos dependentes da temperatura mostraram que havia uma diminuição linear dos tempos de vida de fluorescência com o aumento da temperatura, enquanto que não foi observada qualquer correlação na anisotropia de fluorescência polarizada quando se utilizaram células não marcadas ou marcadas com actina. Durante o tratamento de hipertermia magnética, usando tempos de exposição comparados como os reportados em ensaios clínicos, foram atingidas temperaturas intracelulares de 75 ºC, consideravelmente mais elevadas do que as temperaturas requeridas para induzir morte celular localizada. Em resumo, foi desenvolvida e validada uma nova técnica de medição de temperatura intracelular baseada nas medidas de tempos de vida de fluorescência numa gama de concentrações consideradas não tóxicas.

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Gonçalves, Joana Daniela Ferreira. "Development of multifunctional fucoidan-coated nanoparticles for combined cancer therapy." Master's thesis, 2018. http://hdl.handle.net/10773/25897.

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Magnetic nanoparticles, namely magnetite nanoparticles (NP) have been subject of research and development for application in the biomedical field, especially in magnetic hyperthermia as a therapy for cancer. NPs are often coated with various materials such as silicates and natural or synthetic polymers such as chitosan or polyethylene glycol (PEG), in order to improve biocompatibility but also to enhance their colloidal stability. Fucoidan is a polysaccharide extensively studied for biomedical applications mainly due to its biocompatibility and antitumor properties. In this work, NP of magnetite coated with fucoidan are developed and evaluated for the application in magnetic hyperthermia for cancer treatment, combining magnetic hyperthermia therapy with the antitumor properties of fucoidan. The NP are synthesized by the co-precipitation method at room temperature and, afterwards, subjected to a hydrothermal treatment with different time (1, 2, and 3 h) and temperature (150 or 200 ºC) conditions. The coating of the particles with fucoidan are performed using two methodologies: i) after their synthesis (post-synthesis coating) and ii) simultaneously with the synthesis (in situ coating). Different concentrations of fucoidan are tested in the post-synthesis coatings to evaluate their influence on the physicochemical properties and the thermal efficiency of NP. In the in situ coating syntheses, in addition to evaluating the effect of different concentrations of fucoidan, the influence of the reaction temperature on the functionalization of the NP surface are also studied. NP are characterized in terms of crystallinity and particle size, specific surface area, morphology, colloidal stability and thermal efficiency. In general, NPs synthesized and coated with fucoidan have nearly round shape morphology, and in terms of size NPs with smaller size exhibited a larger surface area. The hydrothermal treatment promoted the increase of NP crystallinity and size as a function of the time and temperature of the hydrothermal treatment. There is also an increase in polydispersity which resulted in a decrease in heating efficiency by hyperthermia. The coating with fucoidan showed to improve the colloidal stability and, consequently, the thermal efficiency due to the reduction of the interactions between the NP. For the synthesis of NP by co-precipitation and post-synthesis coated, better results were obtained in terms of stability, due to the fact that the NPs obtained in situ are smaller and have a greater tendency to agglomerate. The sample giving the best results in the heat release was the one synthesized by co-precipitation at room temperature and coated post-synthesis with a concentration of fucoidan of 2 mg/mL, presenting an Intrinsic Loss Power (ILP) of 2.6 nHm2/kg, which according to literature is considered sufficient in terms of thermal efficiency (2 to 4 nHm2/kg). In addition, this sample had an average size within the recommended range for introduction into the body (less than 20 nm) mainly for its potential application in magnetic hyperthermia. However, NP synthesized and coated simultaneously with 2 mg/mL fucoidan also showed a high thermal efficiency (1.7 nHm2/kg) and its preparation process is simpler. For all of the above described, the results obtained in this work demonstrated that NP of magnetite coated with fucoidan have potential for application in magnetic hyperthermia and may also have, as a consequence of the intrinsic characteristics of fucoidan, antitumoral properties, which allow to potentiate the cancer treatment
As nanopartículas magnéticas, nomeadamente as nanopartículas (NP) de magnetite têm sido alvo de investigação e desenvolvimento para aplicação na área biomédica, em especial na hipertermia magnética como terapia para o cancro. As NP são frequentemente revestidas com diversos materiais, tais como sílicas e polímeros naturais ou sintéticos como a quitosana ou o polietilenoglicol (PEG), visando melhorar a biocompatibilidade mas também potenciar a sua estabilidade coloidal. A fucoidana é um polissacarídeo que tem sido bastante estudado para aplicações biomédicas devido principalmente à sua biocompatibilidade e propriedades antitumorais. Neste trabalho foram desenvolvidas NP de magnetite revestidas com fucoidana e foi avaliado a seu potencial de aplicação em hipertermia magnética, com o intuito de poderem ser usadas na terapia do cancro, combinando a terapia por hipertermia magnética com as propriedades antitumorais da fucoidana. As NP foram sintetizadas pelo método de co-precipitação à temperatura ambiente e, posteriormente, sujeitas a um tratamento hidrotermal com diferentes condições de tempo (1, 2 e 3 h) e temperatura (150 ou 200 ºC). O revestimento das partículas com fucoidana foi feito utilizando duas metodologias: i) após a sua síntese (revestimento pós-síntese) e ii) simultaneamente com a síntese (revestimento in situ). No revestimento pós-síntese testaram-se diferentes concentrações de fucoidana para avaliar a sua influência nas propriedades físico-químicas e na eficiência térmica das NP. Nas sínteses com revestimento in situ para além de avaliar o efeito de diferentes concentrações de fucoidana, estudou-se ainda a influência da temperatura de reação na funcionalização da superfície das NP. As NP foram caracterizadas em termos de cristalinidade e tamanho de partícula, área superficial específica, morfologia, estabilidade coloidal e eficiência térmica. De uma forma geral, as NP sintetizadas e revestidas com fucoidana apresentaram uma morfologia quase esférica, e em termos de tamanho as NP com menor tamanho exibiram uma maior área superficial. O tratamento hidrotermal promoveu o aumento da cristalinidade e do tamanho das NP em função do aumento do tempo e temperatura do tratamento hidrotermal. Ocorreu também um aumento da polidispersividade que se traduziu numa diminuição da eficiência de aquecimento por hipertermia. O revestimento com fucoidana revelou ter influência na dispersão coloidal das NP, sendo que houve uma melhoria na estabilidade coloidal e, consequentemente, na sua eficiência térmica devido à redução das interações entre as NP. Para a sintese de NP por co-precipitação e revestidas pós–síntese, obtiveram-se os melhores resultados em termos de estabilidade, que se deverá ao facto de as NP obtidas in situ serem mais pequenas e possuirem uma maior tendência para se aglomerarem. A amostra que apresentou melhores resultados na libertação de calor foi a sintetizada por co-precipitação à temperatura ambiente e revestida pós-síntese com uma concentração de fucoidana de 2 mg/mL, apresentando um Poder de Libertação Intrínseco (ILP, do inglês Intrinsic Loss Power) de 2.6 nHm2/kg, e que de acordo com a literatura estará na faixa considerada adequada para tratamentos por hipertermia magnética (2 a 4 nHm2/kg). Adicionalmente, esta amostra possui NP com tamanho médio dentro da gama recomendável para a introdução no organismo (inferior a 20 nm) e em especial para a sua potencial aplicação em hipertermia magnética. No entanto, as NP sintetizadas e revestidas simultaneamente com 2 mg/mL de fucoidana apresentaram também uma eficiência térmica elevada (1.7 nHm2/kg ), sendo que o seu processo de preparação é mais simples. Por tudo, o descrito, os resultados obtidos neste trabalho demonstraram que as NP de magnetite revestidas com fucoidana têm potencial para a aplicação em hipertermia magnética podendo ainda ter, dadas as caracteristicas intrinsecas da fucoidana, actividade antitumoral, potenciando o tratamento do cancro
Mestrado em Materiais e Dispositivos Biomédicos

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Дисертації з теми "Hyperthermia cancer magnetic field"

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