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Other publication (peer-review)

Publisher Doctoral thesis (MD; Faculty of Medicine), University of Zurich

Abstract

Background: Functionalized magnetic nanoparticles find increasing applications in a wide variety of biomedical applications. Increasing applications of nanoparticles call for in-depth risk assessments under physiologically relevant conditions, which in turn heavily rely on adequate particle detection and visualization technologies. Particularly the observation of functionalized nanoparticles under physiological conditions remains challenging and often requires surface modification using fluorescence or radioactive markers. This study investigates the surface-functionalization-dependent uptake of magnetic nanoparticles by monocytes and monocyte-derived macrophages in vitro by using confocal reflectance laser scanning microscopy. Methods: This study investigates the uptake of poly(ethylene glycol) and IgG-functionalized carbon-coated iron carbide nanomagnets into phagocytes. Following incubation with nanoparticle suspensions, monocytes and monocyte-derived macrophages are analyzed using confocal laser scanning microscopy. Particles are directly visualized by measuring reflectance and the surface functionalization dependent uptake is analyzed semi-quantitatively using the image processing software Imaris. Correlative light-electron microscopy is used to confirm particle localization. Results: This work demonstrates, that confocal reflectance laser scanning microscopy is a viable method for the label-free visualization of nanomagnets in cell suspensions of monocytes and in monocyte-derived macrophages. It further shows that PEGylated nanomagnets are less rapidly taken up by phagocytes compared to IgG-functionalized particles. Conclusions: Confocal reflectance laser scanning microscopy is a versatile and reliable method for the direct visualization of particle uptake without confounding through surface functionalization usually needed for particle detection and allows semi-quantitative analysis of surface functionalization-dependent particle uptake. (abstract text from doctoral thesis)
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