Nanomaterials have gained great attention for biomedical applications due to their extraordinary physico-chemical and biological properties. The current dissertation presents the design and development of multifunctional nanoparticles for molecular imaging and controlled drug delivery applications which include biodegradable polymeric nanoparticles, superparamagnetic iron oxide nanoparticles (SPION)/polymeric nanocomposite for magnetic resonance imaging (MRI) and drug delivery, manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs)/ SPION/ polymeric nanocomposites for fluorescence imaging, MRI and drug delivery.Bioimaging is an important function of multifunctional nanoparticles in this thesis. Imaging probes were made of SPION and Mn:ZnS QDs for in vitro and in vivo imaging. The SPION have been prepared through a high temperature decomposition method to be used as MRI contrast agent. SPION and Mn:ZnS were encapsulated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles during the particles formation. The hydrophobic model drug, busulphan, was loaded in the PLGA vesicles in the composite particles. T2*-weighted MRI of SPION-Mn:ZnS-PLGA phantoms exhibited enhanced negative contrast with r2* relaxivity of 523 mM-1 s-1. SPION-Mn:ZnS-PLGA-NPs have been successfully applied to enhance the contrast of liver in rat model.The biodegradable and biocompatible poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) was used as matrix materials for polymeric nanoparticles -based drug delivery system. The PEG-PCL nanoparticles have been constructed to encapsulate SPION and therapeutic agent. The encapsulation efficiency of busulphan was found to be ~ 83 %. PEG-PCL nanoparticles showed a sustained release of the loaded busulphan over a period of 10 h. The SPION-PEG-PCL phantoms showed contrast enhancement in T2*-weighted MRI. Fluorescein-labeled PEG-PCL nanoparticles have been observed in the cytoplasm of the murine macrophage cells (J774A) by fluorescence microscopy. Around 100 % cell viability were noticed for PEG-PCL nanoparticles when incubated with HL60 cell line. The in vivo biodistribution of fluorescent tagged PEG-PCL nanoparticles demonstrated accumulation of PEG-PCL nanoparticles in different tissues including lungs, spleen, liver and kidneys after intravenous administration. / <p>QC 20160516</p>

The current methodologies in body scanning diagnostic uses different simultaneous imaging modalities like Ultrasound (US), magnetic resonance imaging (MRI), single photon emission tomography (SPECT) and positron emission tomography (PET). The field requires combination of different modalities for effective use in clinical diagnostics. Such incorporation of different modalities has already been achieved. For example, PET-CT hybrid scanner is designed to acquire align functional and anatomical images and recently US-MRI scanner has successfully shown to improve diagnosis of prostate cancer. The non ionizing radiation hybrid US-MRI is of great interest in health care industry. Further these US and MRI modalities uses different contrast agents like micro-sized gas bubbles (MBs) encapsulated by surfactant for US and superparamagnetic nanoparticles for MRI imaging modalities to further enables new diagnostic opportunities and therapeutic applications. Recently in our 3MiCRON project, we have developed the multimodal contrast agent that could be supported for both US and MRI. This was achieved by coating the magnetic nanoparticles to the poly vinyl alcohol (PVA) surfactant shelled MBs. The nanoparticles in the shell effect the structure can alter the MBs performance as an ultrasound contrast agent. The present thesis is conducted to examine the acoustic and mechanical properties of such multimodal contrast agents. These multimodal contrast agents were prepared by coating the surface of PVA-shelled MBs by two following strategies: (1) The superparamagnetic iron oxide (Fe3O4) nano-particles (SPIONs) were chemically anchored to the surface of poly vinyl alcohol (PVA) shelled MBs namely MBs-chem and (2) in the second strategy the SPIONs were physical entrapped into the PVA shell while formation of PVA surface on the gas bubble were named as MBs-phys. To understand the scattering efficiency and viscoelastic properties of these modified agents, we investigated the backscattering power, attenuation coefficient and phase velocity measurements. Our acoustic experimental results indicate that both the modified MBs and non-modified plain PVA-shelled ultrasound contrast agents have the same echogenic response. The investigation of mechanical properties of modified MBs revealed that the attached SPIONs on the PVA shell has reduced the stiffness of MBs-chem shell, while, the SPIONs inside the shell has increased MBs-phys stiffness. As a result, MBs-chem exhibits soft shell behavior under ultrasound exposure than both MBs-phys. Finally, the images were obtained through the MRI investigations at the department of Radiology, Karolinksa Institute, has demonstrated that both MB types have enough magnetic susceptibility that further provides good detectability in vitro and in vivo. As an outlook, the modified magnetic gas bubbles, i.e. both MBs-chem and MBs-phys can be proposed as a potential contrast agent for both US and MR imaging and can be further utilized in potential therapeutic applications. / <p>QC 20131126</p>

Bereits im 19. Jahrhundert, besonders mit dem deutsch-französischen Krieg von 1870-1871, nahm die Eisenbahn eine zunehmende Rolle in der militärischen Taktik ein. Als der Erste Weltkrieg anfängt sind die Eisenbahnen und ihre Netze die Hauptwerkzeuge der Kriegsführung in Deutschland wie in Frankreich. Material, Menschen, Verpflegung, Waffen, Post werden per Bahn transportiert. Die militärische Machtübernahme der Eisenbahnnetze waren, im Kriegsfall 1914, schon lange vorher geplant gewesen. Die Eisenbahnräume spielen eine wichtige Rolle beim Abschied von Angehörigen. Die Bahnhöfe stehen sinnbildlich als Mittelpunkt der Mobilmachung im August 1914 und sind in fast jede Zeugenaussage erwähnt. Eisenbahnräume sind Zwischenräume zwischwen Heimatfront und Front. Abschied - Spionfieber - Schwarzmarkt - Schwerverletzte Umtausch - / Major logistical and tactical tool during the war, the railway network is devoted to the war effort and, both in Germany and France, is placed under the authority of the military command who manages and reorganises it, making use of regulatory stations, according to the war needs. From a railway perspective, waging war depends on civilians (railway workers, Red Cross) and soldiers (transports routes guardsmen, stations quartermasters generals), ready to step up and shoulder a massive workload and, for some of them, to risk their lives. Civilians (particularly refugees), soldiers (among which soldiers on leave, sick, wounded, repatriated critically wounded), and the vast majority of war equipment (ammunitions, weapons, food supply, mails, ...) need to be transported. Nothing, not even some of these types of travellers, is to jeopardize the war though. A war implying a greater human presence in the railway space, which, in turn, leads to spying, spymania, bombings, evacuations, constructions and destructions of railway facilities, curiosity, gatherings, groups phenomena, unruliness, prostitution, spreading of writings and words of protest, additional travels for the industry and agriculture, and black market. This railway network must be defended and maintained, while at the same time making sure railway workers and soldiers are disciplined and in good moral and physical conditions. Goals and wishes less and less in tune with the reality of the ground, made worse by a dragging war, always increasing the cost in human resources and railway equipments.

Cette thèse présente les travaux de développement de formulations injectables capables de se solidifier in situ, formant ainsi un implant piégeant des microparticules magnétiques en vue du traitement de tumeurs par induction magnétique d'une hyperthermie locale modérée. Nous exposons tout d'abord le contexte physique, biologique et clinique de l'hyperthermie comme traitement anticancéreux, particulièrement des modalités électromagnétiques. Les performances in vitro et in vivo des matériaux et formulations sont alors présentées. L'objet du chapitre suivant est la caractérisation des propriétés physicochimiques, magnétiques, et chauffantes, dans un champ magnétique alternatif (115 kHz, 9 - 12 mT), des microparticules de silice renfermant des nanoparticules d'oxyde de fer superparamagnétiques (SPIONs) et de deux de leurs formulations: un hydrogel d'alginate de sodium et un organogel de poly(éthylène-co-alcool vinylique) dans le diméthylsulfoxide. Finalement, nous présentons le potentiel thérapeutique de 20 minutes d'hyperthermie locale induite après injection de l'organogel superparamagnétique dans un modèle murin sous-cutané de tumeurs nécrosantes de colocarcinome humain.