Publikationen

The development of safe engineered nanoparticles (NPs) requires a detailed understanding of their interaction mechanisms on a cellular level. Therefore, quantification of NP internalization is crucial to predict the potential impact of intracellular NP doses, providing essential information for risk assessment as well as for drug delivery applications. In this study, the internalization of 25 nm and 85 nm silica nanoparticles (SNPs) in alveolar type II cells (A549) was quantified by application of super-resolution STED (stimulated emission depletion) microscopy. Cells were exposed to equal particle number concentrations (9.2×1010 particles mL−1) of each particle size and the sedimentation of particles during exposure was taken into account. Microscopy images revealed that particles of both sizes entered the cells after 5 h incubation in serum supplemented and serum-free medium. According to the in vitro sedimentation, diffusion, and dosimetry (ISDD) model 20–27% of the particles sedimented. In comparison, 102-103 NPs per cell were detected intracellularly serum-containing medium. Furthermore, in the presence of serum, no cytotoxicity was induced by the SNPs. In serum-free medium, large agglomerates of both particle sizes covered the cells whereas only high concentrations (≥ 3.8 × 1012 particles mL−1) of the smaller particles induced cytotoxicity.

Different AlN nanostructures were synthesized by using chemical vapor condensation method. The raw materials were a mixture of Al and NH4Cl powder with different weight ratios as well as Cu and Mn powders, which were used as dopants. The effects of the source materials, dopants, and annealing on optical and structural properties of AlN nanostructures were investigated. Scanning electron microscopy results showed different nanostructures, including nanowires and nanoparticles with different sizes and morphologies. The photoluminescence spectroscopy of the samples was performed at room temperature. Photoluminescence spectra of the samples showed intense peaks in visible regions from undoped, Mn-doped, and Cu-doped samples. Due to the light emission from the samples at different wavelengths, these nanostructures can be used in optoelectronic devices.

In this work, we prepared thin films of aluminum oxide (Al2O3) with different thicknesses, using a wet chemical process. The Al2O3 nanoparticles with an average size of 40 nm were dispersed in water and deposited on soda glass substrates. The morphology of the resulting thin films was characterized by means of scanning electron microscopy. The optical properties of the thin films were studied by measuring reflectance and transmittance. A theoretical description of the reflection and transmission mechanism of the films was developed by measuring the thickness and spectral behavior of the refractive index. Numerical evaluations were used for modeling the optical spectra of the thin films of alumina. By fitting numerical curves to the experimental data, the extinction coefficient and refractive index were obtained. The dielectric constant and optical properties of the colloidal solution of the particles were also studied.

Intercellular communication is a fundamental process in the development and functioning of multicellular organisms. Recently, an essentially new type of intercellular communication, based on thin membrane channels between cells, has been reported. These structures, termed intercellular or tunnelling nanotubes (TNTs), permit the direct exchange of various components or signals (e.g., ions, proteins, or organelles) between non-adjacent cells at distances over 100 μm. Our studies revealed the presence of tunnelling nanotubes in microvascular endothelial cells (HMEC-1). The TNTs were studied with live cell imaging, environmental scanning electron microscopy (ESEM), and coherent anti-Stokes Raman scattering spectroscopy (CARS). Tunneling nanotubes showed marked persistence: the TNTs could connect cells over long distances (up to 150 μm) for several hours. Several cellular organelles were present in TNTs, such as lysosomes and mitochondria. Moreover, we could identify lipid droplets as a novel type of cargo in the TNTs. Under angiogenic conditions (VEGF treatment) the number of lipid droplets increased significantly. Arachidonic acid application not only increased the number of lipid droplets but also tripled the extent of TNT formation. Taken together, our results provide the first demonstration of lipid droplets as a cargo of TNTs and thereby open a new field in intercellular communication research.

Ideal cationic polymers for siRNA delivery could result in its enhanced cellular internalization, escape from endosomal degradation, and rapid release in cell cytoplasm, to facilitate knockdown of the target gene. In this study, we have investigated the ability of an in-house synthesized cationic polyrotaxane to bind siRNA into nanometric complexes. This polymer, which had earlier shown improved transfection of model siRNA (luciferase), was used to improve the cellular internalization of the siRNA molecule with therapeutic implications. In cellular assays, the polymer enhanced the knockdown of a gene involved in the pathogenesis of tuberculosis, when the nanocomplexes were compared with free siRNA. The efficacy and cellular non-toxicity of this polymer encourage its further exploitation in animal models of tuberculosis and other intracellular bacterial infections.

Therapeutic gene silencing using small-interfering RNA (siRNA) for treatment of bacterial infections has been neglected in comparison with cancer and viral infections. The aim of our investigation was to formulate siRNA-loaded nanoparticles, using an established cationic polymethacrylate polymer, to enhance the delivery of siRNA into the cytoplasm of macrophages that host many pathogenic bacterial species, including tuberculosis. Nanoparticles of cationic dimethylaminoethyl methacrylate copolymer (Eudragit® E 100) were successfully formulated and were found to efficiently bind the siRNA molecules (Cy3-siRNA, Bfl1/A1 siRNA). The efficiency of nanoparticles in overcoming cellular barriers to intracellular siRNA delivery and the precise pathway of endocytosis of nanoparticles were both confirmed using confocal microscopy. Through efficient siRNA release into the cytoplasm, the siRNA-loaded nanoparticles enabled a five-fold enhancement in the knockdown efficiency of the endogenous host gene Bfl1/A1, when the formulation was compared with free siRNA. Persistence of Bfl1/A1 is useful for phagolysosomal survival of tuberculosis bacteria in macrophages, and the nanoparticles offer a promising concept for exploitation as an anti-tuberculosis therapy.

In recent years, hundreds of scientific studies have been published regarding gecko-inspired adhesives. The primary reason for this increasing interest lies in the unique properties which are combined in the adhesive system of the gecko: this natural system can quickly and repeatedly adhere to different surface chemistry and roughness without the use of adhesion-mediating fluids. Although these properties seem to be inconspicuous at first, there is no man-made system currently available which successfully combines all of these properties and competes with the biological adhesive system. However, there are many applications which may benefit from an artificial adhesion system inspired by geckos, ranging from climbing robots and handling systems to biomedical patches and household objects.

A novel switchable adhesive, inspired by the gecko's fibrillar dry attachment system, is introduced. It consists of a patterned surface with an array of mushroom-shaped pillars having two distinct heights. The different pillar heights allow control of the pull-off force in two steps by application of a low and a high preload. For low preload, only the long pillars form contact, resulting in a low pull-off force. At higher preload, all pillars form contact, resulting in high pull-off force. Even further loading leads to buckling induced detachment of the pillars which corresponds to extremely low pull-off force. To achieve the respective samples a new fabrication method called double inking is developed, to achieve multiple-height pillar structures. The adhesion performance of the two-step switchable adhesive is analysed at varying preload and for different pillar aspect ratios and height relations. Finally, the deformation behavior of the samples is investigated by in situ monitoring.

A switchable dry adhesive based on a nickel–titanium (NiTi) shape-memory alloy with an adhesive silicone rubber surface has been developed. Although several studies investigate micropatterned, bioinspired adhesive surfaces, very few focus on reversible adhesion. The system here is based on the indentation-induced two-way shape-memory effect in NiTi alloys. NiTi is trained by mechanical deformation through indentation and grinding to elicit a temperature-induced switchable topography with protrusions at high temperature and a flat surface at low temperature. The trained surfaces are coated with either a smooth or a patterned adhesive polydimethylsiloxane (PDMS) layer, resulting in a temperature-induced switchable surface, used for dry adhesion. Adhesion tests show that the temperature-induced topographical change of the NiTi influences the adhesive performance of the hybrid system. For samples with a smooth PDMS layer the transition from flat to structured state reduces adhesion by 56%, and for samples with a micropatterned PDMS layer adhesion is switchable by nearly 100%. Both hybrid systems reveal strong reversibility related to the NiTi martensitic phase transformation, allowing repeated switching between an adhesive and a nonadhesive state. These effects have been discussed in terms of reversible changes in contact area and varying tilt angles of the pillars with respect to the substrate surface.

The genetically determined design of structured functional bio/inorganic materials was investigated by applying a convective assembly approach. Wildtype tobacco mosaic virus (wt TMV) as well as several TMV mutants were organized on substrates over macroscopic-length scales. Depending on the virus type, the self-organization behavior showed pronounced differences in the surface arrangement under the same convective assembly conditions. Additionally, under varying assembly parameters, the virus particles generated structures encompassing morphologies emerging from single micrometer long fibers aligned parallel to the triple-contact line through disordered but dense films to smooth and uniform monolayers. Monolayers with diverse packing densities were used as templates to form TMV/ZnO hybrid materials. The semiconducting properties can be directly designed and tuned by the variation of the template architecture which are reflected in the transistor performance.