Doctor of Philosophy / Department of Chemical Engineering / Keith L. Hohn / Superparamagnetic iron oxide nanoparticle functionalization is an area of intensely active research, with applications across disciplines such as biomedical science and heterogeneous catalysis. This work demonstrates the functionalization of iron oxide nanoparticles with a quasi-monolayer of 11-sulfoundecanoic acid, 10-phosphono-1-decanesulfonic acid, and 11-aminoundecanoic acid. The carboxylic and phosphonic moieties form bonds to the iron oxide particle core, while the sulfonic acid groups face outward where they are available for catalysis. The particles were characterized by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), potentiometric titration, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectrometry (XPS), and dynamic light scattering (DLS). The sulfonic acid functionalized particles were used to catalyze the hydrolysis of sucrose at 80˚C and starch at 130˚C, showing a higher activity per acid site than the traditional solid acid catalyst Amberlyst-15, and comparing well against results reported in the literature for sulfonic acid functionalized mesoporous silicas. In sucrose catalysis reactions, the phosphonic-sulfonic nanoparticles (PSNPs) were seen to be incompletely recovered by an external magnetic field, while the carboxylic-sulfonic nanoparticles (CSNPs) showed a trend of increasing activity over the first four recycle runs. Between the two sulfonic ligands, the phosphonates produced a more tightly packed monolayer, which corresponded to a higher sulfonic acid loading, lower agglomeration, lower recoverability through application of an external magnetic field, and higher activity per acid site for the hydrolysis of starch. Functionalizations with 11-aminoundecanoic acid resulted in some amine groups binding to the surfaces of iron oxide nanoparticles. This amine binding is commonly ignored in iron oxide nanoparticle syntheses and functionalizations for biomedical and catalytic applications, affecting understandings of surface charge and other material properties.

Doctor of Philosophy / Department of Chemistry / Stefan H. Bossmann / Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. Asymptomatic early cancer stages and late diagnosis leads to very low survival rates of pancreatic cancers, compared to other cancers. Treatment options for advanced pancreatic cancer are limited to chemotherapy and/or radiation therapy, as surgical removal of the cancerous tissue becomes impossible at later stages. Therefore, there's a critical need for innovative and improved chemotherapeutic treatment of (late) pancreatic cancers. It is mandatory for successful treatment strategies to overcome the drug resistance associated with pancreatic cancers. Nanotechnology based drug formulations have been providing promising alternatives in cancer treatment due to their selective targeting and accumulation in tumor vasculature, which can be used for efficient delivery of chemotherapeutic agents to tumors and metastases. The research of my thesis is following the principle approach to high therapeutic efficacy that has been first described by Dr. Helmut Ringsdorf in 1975. However, I have extended the use of the Ringsdorf model from polymeric to nanoparticle-based drug carriers by exploring an iron / iron oxide nanoparticle based drug delivery system. A series of drug delivery systems have been synthesized by varying the total numbers and the ratio of the tumor homing peptide sequence CGKRK and the chemotherapeutic drug doxorubicin at the surfaces of Fe/Fe₃O₄-nanoparticles. The cytotoxicity of these nanoformulations was tested against murine pancreatic cancer cell lines (Pan02) to assess their therapeutic capabilities for effective treatments of pancreatic cancers. Healthy mouse fibroblast cells (STO) were also tested for comparison, because an effective chemotherapeutic drug has to be selective towards cancer cells. Optimal Experimental Design methodology was applied to identify the nanoformulation with the highest therapeutic activity. A statistical analysis method known as response surface methodology was carried out to evaluate the in-vitro cytotoxicity data, and to determine whether the chosen experimental parameters truly express the optimized conditions of the nanoparticle based drug delivery system. The overall goal was to optimize the therapeutic efficacy in nanoparticle-based pancreatic cancer treatment. Based on the statistical data, the most effective iron/iron oxide nanoparticle-based drug delivery system has been identified. Its Fe/Fe₃O₄ core has a diameter of 20 nm. The surface of this nanoparticle is loaded with the homing sequence CGKRK (139-142 peptide molecules per nanoparticle surface) and the chemotherapeutic agent doxorubicin (156-159 molecules per surface), This nanoplatform is a promising candidate for the nanoparticle-based chemotherapy of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult type of cancer to treat, due to late diagnosis which is a result of vague symptoms and lack of biomarkers, as well as refractory behavior toward current treatment protocols. Imaging of the disease progression therefore plays a crucial role in identifying potentially curable PDAC patients at an early stage. Nanoparticle-based contrast agents have shown multimodal capabilities and potential to enhance the contrast of previously undetectable pathological changes, including PDAC. In this master’s thesis study, an iron oxide nanoparticle (IONP) was evaluated as a potential multimodal contrast agent for both photoacoustic imaging (PAI) and magnetic resonance imaging (MRI). The investigated particle was composed of Fe3O4 with a hydrodynamic size of 418.5 nm and a zeta potential of -27.7 mV. In the agarose suspended IONP phantom studies, the IONP demonstrated a two-fold higher T2 contrast compared to commercial IONP VivoTrax (Magnetic Insight), as well as generating strong and stable photoacoustic signal throughout the first near-infrared window (700 to 1000 nm). Based on this thesis’ proof of concept study, Fe3O4 IONP showed good potential as multimodal contrast agent for MRI and PAI. Future work consists of modification of the particle composition and in vivo imaging on animals to evaluate the application in PDAC diagnostics.

The study of self-sensing cementitious materials is a constantly expanding topic of study in the materials and civil engineering fields and refers to the creation and utilization of cement-based materials (including cement paste, cement mortar, and concrete) that are capable of sensing (i.e. measuring) stress and strain states without the use of embedded or attached sensors. With the inclusion of electrically conductive fillers, cementitious materials can become truly self-sensing. Previous researchers have provided only qualitative studies of self-sensing material stress-electrical response. The overall goal of this research was to modify and apply previously developed predictive models on cylinder compression test data in order to provide a means to quantify stress-strain behavior from electrical response. The Vipulanandan and Mohammed (2015) stress-resistivity model was selected and modified to predict the stress state, up to yield, of cement cylinders enhanced with nanoscale iron(III) oxide (nanoFe2O3) particles based on three mix design parameters: nanoFe2O3 content, water-cement ratio, and curing time. With the addition of a nonlinear model, parameter values were obtained and compiled for each combination of nanoFe2O3 content and water-cement ratio for the 28-day cured cylinders. This research provides a procedure and lays the framework for future expansion of the predictive model.

Ces travaux de thèse s'inscrivent dans le contexte de l'imagerie moléculaire, qui vise à adapter les traitements de pathologies à la variabilité de chaque patient, grâce à l'imagerie de biomarqueurs cellulaires ou moléculaires. En particulier, l'imagerie par résonance magnétique (IRM) couplée a des nanoparticules d’oxyde de fer innovantes pourrait permettre de relever un tel défi.Cette thèse se concentre sur l'étude d'une nouvelle classe d'agents de contraste à base d'oxyde de fer pour l'IRM à haut champ magnétique. En effet, les magnétosomes sont des vésicules d’oxyde de fer produites naturellement par des bactéries appelées bactéries magnétotactiques. De telles bactéries synthétisent ces vésicules magnétiques et les alignent comme l'aiguille d'une boussole, ce qui facilite leur navigation dans les sédiments. Ces bactéries produisent donc des magnétosomes aux propriétés magnétiques exceptionnelles: 50 nm de diamètre, mono-cristallin, mono-domaine magnétique et avec une haute magnétisation à saturation. De plus, une grande variété de souches bactériennes existent dans la nature, et produisent, avec une grande stabilité, des magnétosomes dont la taille, la forme, et le contenu chimique, sont déterminés génétiquement. Enfin, les magnétosomes sont naturellement porteurs d'une membrane bi-lipidique dont le contenu est également déterminé génétiquement. Récemment, le contenu protéique de la membrane des magnétosomes a été mis à jour, ouvrant la voie à la fonctionnalisation de cette dernière par fusion des gènes codant pour des protéines présentes abondamment à la membrane avec ceux codant pour un peptide d’intérêt.Ainsi, l'utilisation de ces micro-organismes pour produire des agents de contraste innovants et fonctionnalisés pour l'imagerie moléculaire par IRM, et les applications qui en découlent, ont été étudiées pendant cette thèse. La production et l'ingénierie des magnétosomes a été réalisée par nos collègues du Laboratoire de Bioénergétique Cellulaire (LBC, CEA Cadarache), et sera présentée et discutée. Des magnétosomes sauvages ont d'abord été caractérisés en tant qu'agents de contraste pour l'IRM. De tel magnétosomes présentent des propriétés contrastantes très intéressantes pour l'IRM, ce qui a été validé à la fois in vitro puis in vivo. L'étude de faisabilité de la production d'un agent de contraste pour l'imagerie moléculaire par IRM en une seule étape, à l'aide des bactéries magnétotactiques, a été réalisée sur un modèle de souris porteur de glioblastome. Sachant par la littérature que les cellules tumorales sur-expriment les intégrines anb3, et que ces dernières peuvent être ciblées par le peptide RGD, il a été choisi de produire des magnétosomes exprimant le peptide RGD à leur membrane. L'affinité de tels magnétosomes pour les cellules tumorales U87 a été vérifiée in vitro, et démontré in vivo par IRM puis cross-validé par histologie. / This work takes place in the context of molecular imaging, which aims at tailoring medical treatments and therapies to the individual context by revealing molecular or cellular phenomenon of medical interest in the less invasive manner. In particular, it can be acheived with MRI molecular imaging using engineered iron-oxide contrast agent.This PhD thesis focuses on the study of a new class of iron-oxide contrast agent for high field MRI. Indeed, magnetosomes are natural iron-oxide vesicles produced by magnetotactic bacteria. These bacteria synthesized such magnetic vesicles and ordered them like a nano-compass in order to facilitate their navigation in sediments. This explains why magnetosomes are awarded with tremendous magnetic properties: around 50 nm, mono-crystalline, single magnetic domain and high saturation magnetization. Furthermore, a wide variety of bacterial strains exist in nature and size and shape of magnetosomes are highly stable within strain and can be very different between strains. Finally, magnetosomes are naturally coated with a bilipidic membrane whose content is genetically determined. Lately, researchers have unravelled magnetosomes membrane protein contents, opening the way to create functionnalized magnetosomes thanks to fusion of the gene coding for a protein of interest with the gene coding for an abundant protein at magnetosomes membrane.A new alternative path using living organisms to tackle the production of engineered high effciency molecular imaging probes have been investigated with magnetotactic bacteria in this PhD. The production and engineering of magnetosomes have been carried out by our partner, the Laboratoire de Bio-energétique Cellulaire (LBC, CEA Cadarache), and will be presented and discussed. We then characterized magnetosomes as contrast agent for high field MRI. We showed they present very promising contrasting properties in vitro, and assessed this observation in vivo by establishing they can be used as effcient blood pool agent after intravenous injection. Afterward, we applied the concept of producing engineered MRI molecular imaging probes in a single step by bacteria, to a mouse model of glioblastoma. Knowing that tumor cells can be actively targeted through anb3 integrins by RGD, we produced RGD functionnalized magnetosomes. We started from showing these RGD magnetosomes have a good affnity for U87 cell in vitro, prior to demonstrate it in vivo on orthotopic U87 mouse model. This in vivo affnity being fnally cross-validated with histology.

The synthesis, characterization and biological evaluation of different graphene-based nanoparticles with potential biomedical applications are explored. The results presented within this work show that eukaryotic cells can respond differently not only to different types of nanoparticles, but also identify slight differences in the morphology of nanoparticles, such as size. This highlights the great importance of the synthesis and thorough characterization of nanoparticles in the design of effective nanoparticle platforms for biological applications. In order to test the influence of morphology of graphene-based nanoparticles on the cell response, nanoparticles with different sizes were synthesized and tested on different cells. The synthesis of spherical iron-oxide nanoparticles coated with graphene was accomplished using a colloidal chemistry route. This synthesis route was able to render nanoparticle samples with narrow size distributions, which can be taken as monodispersed. Four different samples varying in diameter from 10 to 20 nm were produced and the material was systematically characterized prior to the biological tests. The characterization of the material suggests that the iron oxide nanoparticles consist of a mix of both magnetite and maghemite phases and are coated with a thin graphitic layer. All samples presented functional groups and were similar in all aspects except in diameter. The results suggest that cells can respond differently even to small differences in the size of the nanoparticles. An in situ study of the coating of the iron-oxide nanoparticles using a transmission electron microscope revealed that it is possible to further graphitize the remaining oleic acid on the nanoparticles. The thickness of the graphitic coating was controlled by varying the amount of oleic acid on the nanoparticles. The in situ observations using an electron beam were reproduced by annealing the nanoparticles in a dynamic vacuum. This procedure showed that it is not only possible to coat large amounts of iron oxide nanoparticles with graphene using oleic acid, but also to improved their magnetic properties for other applications such as hyperthermia. This study therefore revealed a facile route to grow 2D graphene takes on substrates using oleic acid as a precursor. The synthesis of nanographene oxide nanoparticles of different sizes was in a second approach accomplished by using the Hummers method to oxidize and expand commercially available graphite. The size of the oxidized graphite was adjusted by sonicating the samples for different periods of time. The material was also thoroughly characterized and demonstrated to have two distinctive average size distributions and possess functional groups. The results suggest that different size flakes can trigger different cell response. The synthesis, characterization and biological evaluation of graphene nanoshells were performed. The graphene nanoshells were produced by using magnesia nanoparticles as a template to the graphene nanoshells. The coating of magnesia with graphene layers was accomplished using chemical vapor deposition. The nanoshells were obtained by removing the magnesia core. The size of the nanoshells was determined by the size of the magnesia nanoparticles and presented a broad size distribution since the diameter of the magnesia nanoparticles could not be controlled. The nanoshells were also characterized and the biological evaluation was performed in the Swiss Federal Laboratories for Materials Science and Technology (EMPA), in Switzerland. The results suggest that despite inducing the production of reactive oxygen species on cells, the nanoshells did not impede cell proliferation. / Die Herstellung, Charakterisierung und biologische Auswertung von verschiedenen Graphen-basierten Nanopartikeln mit einer potenziellen biomedizinischen Anwendung wurden erforscht. Die vorgestellten Ergebnisse im Rahmen dieser Arbeit zeigen, dass eukaryotische Zellen unterschiedlich reagieren können, wenn sie mit Nanopartikeln unterschiedlicher Morphologie interagieren. Die Zellen können geringe Unterschiede in der Morphologie, insbesondere der Größe der Nanopartikeln, identifizieren. Dies unterstreicht den Einfluss der Herstellungsmethoden und die Notwendigkeit einer gründlichen Charakterisierung, um ein effektives Design von Nanopartikeln für biologische Anwendungen zu erreichen. Um den Einfluss der Größe von Graphen-basierten Nanopartikel auf das Zellverhalten zu erforschen, wurden verschiedene Graphen-beschichte Eisenoxid-Nanopartikelproben durch eine kolloidchemische Methode hergestellt. Dieses Herstellungsverfahren ermöglicht die Synthese von Nanopartikeln mit engen Größenverteilungen, die als monodispers gelten können. Vier Proben mit unterschiedlichen Durchmessern (von 10 bis 20 nm) wurden hergestellt und vor den biologischen Untersuchungen systematisch charakterisiert. Die Probencharakterisierung deutet auf eine Mischung aus Magnetit- und Maghemit-Kristallphasen hin, außerdem besitzen die Nanopartikel eine dünne Graphitschicht. Die spektroskopischen Ergebnisse auch zeigen außerdem, dass alle Proben funktionelle Gruppen auf ihrer Oberfläche besitzen, sodass sie in allen Aspekten, außer Morphologie (Durchmesser), ähnlich sind. Die biologischen Untersuchungen deuten darauf hin, dass Zellen unterschiedliche Größen von Eisenoxid-Nanopartikeln reagieren können. Ein in situ Untersuchung der Beschichtung der Eisenoxid-Nanopartikel wurde mit einem Transmissionelektronenmikroskop durchgeführt. Die Ergebnisse zeigen, dass eine dünne Schicht von Ölsäure aus dem Syntheseprozess auf den Nanopartikeln verbleibt. Diese Schicht kann mit einem Elektronstrahl in Graphen umgewandelt werden. Die Dicke der Graphitschicht auf den Nanopartikeln kann durch die Menge der eingesetzten Ölsäure kontrolliert werden. Die in situ Beobachtungen der Graphenumwandlung konnte durch erhitzen der Nanopartikeln in einem dynamischen Vakuum reproduziert werden. Das Brennen der Eisenoxid-Nanopartikel ermöglicht nicht nur die Graphitisierung der Ölsäure, sondern auch eine Verbesserung der magnetischen Eigenschaften der Nanopartikel für weitere Anwendungen, z. B. der Hyperthermie. Die Umwandlung der Ölsäure in Graphen konnte so als relativ einfaches Verfahren der Beschichtung von zweidimensionalen (2D) Substraten etabliert werden. Die Herstellung von Nanographenoxid mit unterschiedlichen Größen wurde mit der Hummers-Method durchgeführt. Die unterschiedlichen Größen der Nanographenoxidpartikel wurde durch eine Behandlung in Ultraschallbad erreicht. Zwei Proben mit deutlicher Verteilung wurden mit mehreren Verfahren charakterisiert. Beide Proben haben Nanographenoxid Nanoteilchen mit verschiedenen funktionellen Gruppen. Die biologische Charakterisierung deutet darauf hin, dass unterschiedliche Größen des Nanographens ein unterschiedliches Zellverhalten auslösen. Abschließend, wurde die Herstellung, Charakterisierung und biologische Auswertung von Graphen-Nanoschalen durchgeführt. Die Graphen-Nanoschalen wurden mit Magnesiumoxid-Nanopartikeln als Template hergestellt. Die Beschichtung des Magnesia mit Graphen erforgte durch die chemische Gasphasenabscheidung. Die Nanoschalen wurden durch Entfernen des Magnesia-Kerns erhalten. Die Größe der Nanohüllen ist durch die Größe der Magnesia-Kerns bestimmt und zeigt eine breite Verteilung, da der Durchmesser der Magnesiumoxid-Nanopartikel gegeben war. Die Nanoschalen wurden ebenfalls mit Infrarot- und Röntgen Photoemissionspektroskopie charakterisiert und die biologische Bewertung wurde im Eidgenössische Materialprüfungs- und Forschungsanstalt (EMPA) durchgeführt, in der Schweiz. Die Ergebnisse zeigen, dass zwar die Produktion von reaktiven Sauerstoffspezies in den Zellen ausgelöst wird, diese sich aber weiterhin vermehren können.

Various nano-fillers can introduce specific functions into polymer and expand their application areas. Myriad properties, such as mechanical, electrical, thermal, or magnetic properties can be combined with original polymer characteristics, including flexible, light weight, and ease of use. These composites can be used to produce multi-functional fibers as the next generation textile or fabrics. In this research, Polyacrylonitrile (PAN) is adopted as the main polymer with different nano-fillers, such as carbon nanotube (CNT), iron oxide nanoparticle, and graphene oxide nanoribbon (GONR). Using gel-spinning technology, PAN-based composite fibers are fabricated in single- or bi-component fibers. Fibers are also characterized for their structure, morphology, mechanical properties, as well as for their electrical, thermal, or magnetic properties. For example, bi-component fibers with polymer sheath and polymer-CNT core as well as polymer-CNT sheath and polymer core are processed. With electrical and thermal conductivity introduced by CNT, such bi-components fibers can be applied for wearable electronics or for thermal management. Joule-heating effect owing to applied electrical current on single component PAN/CNT fibers is also investigated. With controllable electrical conductivity and fiber temperature, this active functional fiber can be applied for temperature regulation fibers or new carbon fiber manufacturing process. Another example is magnetic fiber with superparamagnetic iron oxide nano-particles. These novel magnetic fibers with high strength can be used for actuator, inductors, EMI shielding, or microwave absorption. GONR is also discussed and used to reinforce PAN-based fibers. Several theoretical models are considered to analyze the observed results.

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.

The synthesis, characterization and biological evaluation of different graphene-based nanoparticles with potential biomedical applications are explored. The results presented within this work show that eukaryotic cells can respond differently not only to different types of nanoparticles, but also identify slight differences in the morphology of nanoparticles, such as size. This highlights the great importance of the synthesis and thorough characterization of nanoparticles in the design of effective nanoparticle platforms for biological applications. In order to test the influence of morphology of graphene-based nanoparticles on the cell response, nanoparticles with different sizes were synthesized and tested on different cells. The synthesis of spherical iron-oxide nanoparticles coated with graphene was accomplished using a colloidal chemistry route. This synthesis route was able to render nanoparticle samples with narrow size distributions, which can be taken as monodispersed. Four different samples varying in diameter from 10 to 20 nm were produced and the material was systematically characterized prior to the biological tests. The characterization of the material suggests that the iron oxide nanoparticles consist of a mix of both magnetite and maghemite phases and are coated with a thin graphitic layer. All samples presented functional groups and were similar in all aspects except in diameter. The results suggest that cells can respond differently even to small differences in the size of the nanoparticles. An in situ study of the coating of the iron-oxide nanoparticles using a transmission electron microscope revealed that it is possible to further graphitize the remaining oleic acid on the nanoparticles. The thickness of the graphitic coating was controlled by varying the amount of oleic acid on the nanoparticles. The in situ observations using an electron beam were reproduced by annealing the nanoparticles in a dynamic vacuum. This procedure showed that it is not only possible to coat large amounts of iron oxide nanoparticles with graphene using oleic acid, but also to improved their magnetic properties for other applications such as hyperthermia. This study therefore revealed a facile route to grow 2D graphene takes on substrates using oleic acid as a precursor. The synthesis of nanographene oxide nanoparticles of different sizes was in a second approach accomplished by using the Hummers method to oxidize and expand commercially available graphite. The size of the oxidized graphite was adjusted by sonicating the samples for different periods of time. The material was also thoroughly characterized and demonstrated to have two distinctive average size distributions and possess functional groups. The results suggest that different size flakes can trigger different cell response. The synthesis, characterization and biological evaluation of graphene nanoshells were performed. The graphene nanoshells were produced by using magnesia nanoparticles as a template to the graphene nanoshells. The coating of magnesia with graphene layers was accomplished using chemical vapor deposition. The nanoshells were obtained by removing the magnesia core. The size of the nanoshells was determined by the size of the magnesia nanoparticles and presented a broad size distribution since the diameter of the magnesia nanoparticles could not be controlled. The nanoshells were also characterized and the biological evaluation was performed in the Swiss Federal Laboratories for Materials Science and Technology (EMPA), in Switzerland. The results suggest that despite inducing the production of reactive oxygen species on cells, the nanoshells did not impede cell proliferation. / Die Herstellung, Charakterisierung und biologische Auswertung von verschiedenen Graphen-basierten Nanopartikeln mit einer potenziellen biomedizinischen Anwendung wurden erforscht. Die vorgestellten Ergebnisse im Rahmen dieser Arbeit zeigen, dass eukaryotische Zellen unterschiedlich reagieren können, wenn sie mit Nanopartikeln unterschiedlicher Morphologie interagieren. Die Zellen können geringe Unterschiede in der Morphologie, insbesondere der Größe der Nanopartikeln, identifizieren. Dies unterstreicht den Einfluss der Herstellungsmethoden und die Notwendigkeit einer gründlichen Charakterisierung, um ein effektives Design von Nanopartikeln für biologische Anwendungen zu erreichen. Um den Einfluss der Größe von Graphen-basierten Nanopartikel auf das Zellverhalten zu erforschen, wurden verschiedene Graphen-beschichte Eisenoxid-Nanopartikelproben durch eine kolloidchemische Methode hergestellt. Dieses Herstellungsverfahren ermöglicht die Synthese von Nanopartikeln mit engen Größenverteilungen, die als monodispers gelten können. Vier Proben mit unterschiedlichen Durchmessern (von 10 bis 20 nm) wurden hergestellt und vor den biologischen Untersuchungen systematisch charakterisiert. Die Probencharakterisierung deutet auf eine Mischung aus Magnetit- und Maghemit-Kristallphasen hin, außerdem besitzen die Nanopartikel eine dünne Graphitschicht. Die spektroskopischen Ergebnisse auch zeigen außerdem, dass alle Proben funktionelle Gruppen auf ihrer Oberfläche besitzen, sodass sie in allen Aspekten, außer Morphologie (Durchmesser), ähnlich sind. Die biologischen Untersuchungen deuten darauf hin, dass Zellen unterschiedliche Größen von Eisenoxid-Nanopartikeln reagieren können. Ein in situ Untersuchung der Beschichtung der Eisenoxid-Nanopartikel wurde mit einem Transmissionelektronenmikroskop durchgeführt. Die Ergebnisse zeigen, dass eine dünne Schicht von Ölsäure aus dem Syntheseprozess auf den Nanopartikeln verbleibt. Diese Schicht kann mit einem Elektronstrahl in Graphen umgewandelt werden. Die Dicke der Graphitschicht auf den Nanopartikeln kann durch die Menge der eingesetzten Ölsäure kontrolliert werden. Die in situ Beobachtungen der Graphenumwandlung konnte durch erhitzen der Nanopartikeln in einem dynamischen Vakuum reproduziert werden. Das Brennen der Eisenoxid-Nanopartikel ermöglicht nicht nur die Graphitisierung der Ölsäure, sondern auch eine Verbesserung der magnetischen Eigenschaften der Nanopartikel für weitere Anwendungen, z. B. der Hyperthermie. Die Umwandlung der Ölsäure in Graphen konnte so als relativ einfaches Verfahren der Beschichtung von zweidimensionalen (2D) Substraten etabliert werden. Die Herstellung von Nanographenoxid mit unterschiedlichen Größen wurde mit der Hummers-Method durchgeführt. Die unterschiedlichen Größen der Nanographenoxidpartikel wurde durch eine Behandlung in Ultraschallbad erreicht. Zwei Proben mit deutlicher Verteilung wurden mit mehreren Verfahren charakterisiert. Beide Proben haben Nanographenoxid Nanoteilchen mit verschiedenen funktionellen Gruppen. Die biologische Charakterisierung deutet darauf hin, dass unterschiedliche Größen des Nanographens ein unterschiedliches Zellverhalten auslösen. Abschließend, wurde die Herstellung, Charakterisierung und biologische Auswertung von Graphen-Nanoschalen durchgeführt. Die Graphen-Nanoschalen wurden mit Magnesiumoxid-Nanopartikeln als Template hergestellt. Die Beschichtung des Magnesia mit Graphen erforgte durch die chemische Gasphasenabscheidung. Die Nanoschalen wurden durch Entfernen des Magnesia-Kerns erhalten. Die Größe der Nanohüllen ist durch die Größe der Magnesia-Kerns bestimmt und zeigt eine breite Verteilung, da der Durchmesser der Magnesiumoxid-Nanopartikel gegeben war. Die Nanoschalen wurden ebenfalls mit Infrarot- und Röntgen Photoemissionspektroskopie charakterisiert und die biologische Bewertung wurde im Eidgenössische Materialprüfungs- und Forschungsanstalt (EMPA) durchgeführt, in der Schweiz. Die Ergebnisse zeigen, dass zwar die Produktion von reaktiven Sauerstoffspezies in den Zellen ausgelöst wird, diese sich aber weiterhin vermehren können.