@PhdThesis{duepublico_mods_00075284, author = {Olejnik, Mateusz}, title = {Synthese von Zinkoxid-, Titandioxid- und Silica-Partikeln mit definierter Form, Gr{\"o}{\ss}e und Kristallinit{\"a}t und ihre zellbiologischen Effekte}, year = {2021}, month = {Jan}, day = {27}, abstract = {In this work the synthesis and characterization of various oxide particle systems was presented. These systems were further tested on lung macrophages (NR8383) towards toxicological effects. Five different oxide particle systems were chosen as model particles for toxicological studies. These were SiO2 (amorphous silica and quartz), ZnO and TiO2 (anatase and rutile). For particle synthesis, various wet chemical methods were performed, with the goal to produce monodisperse and colloidally stabile particles in a reproducible way. The focus of these syntheses was to obtain chemically identical particles, which differed in size, shape and crystallinity. Thus enabled a comparative study of the influence of these particle parameters on cell viability. In the synthesis of all oxide particle systems, three particle size ranges (nano, submicro and micrometer) and two particle shapes (spheres and rods) were obtained. Depending on the type of synthesis, the particles were electrostatically- or sterically-stabilized and tested for purity, shape, and chemical and crystallographic composition using various methods, including colloid-chemical, electron microscopic, spectroscopic and crystallographic methods. In the first part of the thesis, the St{\"o}ber process resulted in preparing "naked" (non-functionalized) silica spheres with three particle sizes, through targeted hydrolysis and subsequent polycondensation of tetraethylorthosilicate (TEOS). The particle size and shape of silica spheres could be controlled by the concentration of starting materials and reaction temperature. For the synthesis of silica nanospheres and submicrospheres the temperature was increased accordingly. Since only spherical amorphous silica particles were obtained, according to the classic St{\"o}ber method, further addition of a cationic surfactant (CTAB) to the reaction mixture was necessary to obtain a directed anisotropic growth of the particles. After a slight modification of the literature-known protocols, CTAB-functionalized silica submicrorods and microrods were successfully synthesized. The control of particle length during synthesis could be achieved through the molar ratio of reactants and by adjustment of the stirring speed. However, with the modified St{\"o}ber process, it was not possible to obtain CTAB-silica nanorods with an average particle length of ≤100 nm. Since CTAB is cytotoxic, and thus CTAB-functionalized silica rods were unsuitable for further biological studies, a strategy to remove CTAB from the particles was developed. ``Naked'' (CTAB-free) silica rods obtained in this way were examined for the presence of CTAB on their surface by IR spectroscopy and elemental analysis. Furthermore, the DLS measurements confirmed that the particles were electrostatically stabile as in the case of amorphous silica spheres. An additional type of rod-shaped silica particles could be produced based on the microemulsion method. In the presence of PVP, in a water-oil emulsion (1-pentanol / water mixture), a directional growth of polymer-functionalized silica large rods (with an average particle length of 3.5 $\mu$m) could be achieved. After fluorescence labelling of 6 types of the silica particles, with dye-coupled polymers (CMC-F or PEI-FITC), the cellular uptake of the particles could be followed by confocal laser scanning microscopy (CLSM). In contrast to amorphous silica particles, which were easily obtained in the sol-gel process using the St{\"o}ber method, the synthesis of monodisperse quartz particles with defined shape and size could not be guaranteed, due to lack of dispersibility and loss of the original morphology after crystallization. By using common solid-state chemistry methods, such as hydrothermal syntheses or high-temperature processes, it was possible to convert the amorphous silica particles to quartz particles or cristobalite particles, however, they demonstrated a tendency to form larger crystalline SiO2 particles. Internal crystallization of the quartz particles from amorphous silica particles was therefore not possible without changing the original particle shape. In the next part of the thesis, PVP-ZnO particles in wurtzite structure were successfully synthesized from zinc salts and in the presence of PVP in two one-pot syntheses. These were performed in dimethylformamide (DMF) and in polyols (polyol process). Although synthesis of the PVP-ZnO nanospheres and PVP-ZnO nanorods was carried out as described in literature, an optimization of synthesis was already needed to obtain PVP-ZnO microspheres and PVP-ZnO microrods with defined parameters. Our own investigations on the influence of reaction parameters on particle properties in DMF one-pot synthesis demonstrated that the amount of water in the reaction mixture was critical to control shape of the particles. On the other hand, shortening of the reaction time enabled to control particle size with unchanged reaction conditions and led to successful synthesis of PVP-ZnO submicrospheres. In-depth studies indicated that a change in the amounts of zinc salt and water, in the polyol process, did not result in formation of PVP functionalized ZnO submicrorods. The quantitative analysis of the release of Zn2+ ions from the five types of PVP-ZnO particles was investigated in different environments, i.e., ultrapure water, RPMI medium and simulated lysosomal medium. Contrary to the expectations, no significant differences in the release of Zn2+ ions in ultrapure water and biological media, correlated with size and shape of the particles, were found. Hypothetically, the increased surface area of ZnO nanoparticles, compared to submicro- and microparticles, should lead to a significantly higher release of Zn2+ ions. Overall, the dissolution of ZnO particles in biological media was higher (up to 17{\%}) than in ultrapure water (up to 7{\%}). As expected, dissolution studies in the simulated lysosomal medium confirmed that ZnO particles were almost completely dissolved after 1 hour of incubation in the acidic medium (pH <5). The last aim of the thesis was to synthesize TiO2 particles in two different polymorphic forms: anatase and rutile. Although, TiO2 particles may exist in three crystallographic modifications: anatase, rutile and brookite, they can also be produced in an amorphous form or with mixed crystalline phases in a wet-chemical method. Control of the three target particle sizes, two particle shapes (spheres and rods) and two crystal structures (anatase and rutile) led to synthesis of twelve different types of TiO2 particles. Many, however, not all, types of TiO2 particles could be synthesized in this work. Results of this work show that synthesis of spherical anatase particles (in three target sizes) was possible, in contrary to anatase rods. After the sol-gel process, amorphous ``naked'' submicrospheres and microspheres could be obtained from titanium alcoholates. Next, they were crystallized to anatase by calcination at 500 ˚C for 1 h, without losing their shape and colloidal stability. On the other hand, preparation of significantly smaller crystalline anatase nanospheres required harsher reaction conditions and was carried out by converting titanium alcoholates in concentrated acetic acid at 200 ˚C in the solvothermal synthesis. Using the polyol method, it was possible to synthesize amorphous TiO2 large rods which, analogous to PVP silica large rods, were very promising as model particles for potential toxicological studies on fibrous particles (WHO-fibres). The presence of chloride ions in the reaction mixture was critical for the formation of rutile particles with defined shape and crystal structure. Based on the modifications of well-known syntheses of rutile particles, it was possible to show that the formation of rutile nanorods from titanium alcoholates in aqueous hydrochloric acid was possible within 24 h at room temperature. Interestingly, conversion of the same reactants under hydrothermal conditions favored the growth of rutile particles. This resulted in the formation of rutile submicrorods at 200 ˚C already after 2 hours. A further increase in the reaction time from 2 hours to 24 hours, with the same reaction conditions, did not enhance the growth of rutile microrods. Another Modification of the well-known procedure for synthesis of rutile particles led to the production of rutile microspheres. The particles were synthesized with the addition of HCl to the hydrolyzed solution of TiCl4 followed by subsequent hydrothermal synthesis at 100 ˚C for 24 h. Obtained rutile particles were generally spherical and crystallographically consisted of rod-like rutile nanocrystallites assembled to form the microspheres. Compared to rutile microspheres, the anatase microspheres were composed of spherical nanocrystallites.}, doi = {10.17185/duepublico/75284}, url = {https://duepublico2.uni-due.de/receive/duepublico_mods_00075284}, url = {https://doi.org/10.17185/duepublico/75284}, file = {:https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00075013/Diss_Olejnik_2021.pdf:PDF}, language = {de} }