Engineered core-shell nanoparticles for biomedical applications

Abstract: The necessity for synthesis of nanoparticles with well controlled size and morphology emerged with the development in recent years of novel advanced applications especially in biomedical related fields. These applications require nanoparticles with more complex architecture such as multifunctional nanoparticles (i.e. core–shell structures) that can carry several components with different embedded functionalities. In this thesis, we developed core–shell nanoparticles (CSNPs) with finely tuned silica shell on iron oxide core as model system for advanced applications in nanomedicine such as MRI, drug delivery and hyperthermia.The synthesis of monodispersed, and well separated, single iron oxide core–silica (SiO2) shell nanoparticles for biomedical applications is still a challenge. Substantial amount of aggregated and multicore CSNPs are generally the undesired outcome. In this thesis, synthesis of monodispersed, free of necking, single core iron oxide-SiO2 different distinct overall size and tuneable shell thickness was performed using an inverse microemulsion method. The influence of the reaction time, hydrodynamic conditions and precursor concentration on the synthesis process and thickness of the silica layer was investigated and the process was optimised. The residual reactions during the post synthesis processing were inhibited using a combination of pH adjustment and alternating shock freezing with ultracentrifuging.The second part of the thesis is concerning thorough characterisation of the CSNPs with different shell thickness. The non-aggregated tuneable shell CSNPs maintained the superparamagnetic character of the cores with high magnetisation, showing great potential for their applications in nanomedicine. Magnetic measurements and relaxivity tests were performed and the comparison of the CSNPs with commercial products revealed the fact that relaxation time ratios (r2/r1) obtained are higher than those of the commercially available MRI contrast agents which indicates a better T2 contrast.In the last part of the thesis the in-vitro toxicity investigation results are reported. For the investigation of cytotoxicity (3- 4, 5-dimethyldiazol-2-yl)-2, 5 diphenyl-tetrazolium bromide (MTT) assay was performed and the secretion of pro-inflammatory cytokines TNF-α and IL-6 was determined using enzyme-linked immunosorbent assay (ELISA). The cells were exposed to a wide range of concentrations of nanoparticles (between 0.5 μg/ml to 100 μg/ml). The cell toxicity results indicated no severe toxic effects on human monocyte-derived macrophages (HMDM) as model system. The internalisation of the nanoparticles by HMDM was monitored using transmission electron microscopy (TEM).The CSNPs have the capacity of forming stable colloidal dispersions at physiological pH, with desired magnetic properties, low toxicity, and the potential for further functionalisation via surface modification of the silica shell or by adding new components (i.e. quantum dots, therapeutics). These characteristics make them highly promising for drug delivery, medical imaging, hyperthermia, magnetic cell marking and cell separation as well as many other biomedical applications.