Publikationen

Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood–air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene-glycol-coated (PEGylated) and citrate/tannic-acid-coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.

In this study, a novel approach for preparation of green fluorescent protein (GFP)-doped silica nanoparticles with a narrow size distribution is presented. GFP was chosen as a model protein due to its autofluorescence. Protein-doped nanoparticles have a high application potential in the field of intracellular protein delivery. In addition, fluorescently labelled particles can be used for bioimaging. The size of these protein-doped nanoparticles was adjusted from 15 to 35 nm using a multistep synthesis process, comprising the particle core synthesis followed by shell regrowth steps. GFP was selectively incorporated into the silica matrix of either the core or the shell or both by a one-pot reaction. The obtained nanoparticles were characterised by determination of particle size, hydrodynamic diameter, ζ-potential, fluorescence and quantum yield. The measurements showed that the fluorescence of GFP was maintained during particle synthesis. Cellular uptake experiments demonstrated that the GFP-doped nanoparticles can be used as stable and effective fluorescent probes. The study reveals the potential of the chosen approach for incorporation of functional biological macromolecules into silica nanoparticles, which opens novel application fields like intracellular protein delivery.

In recent years, fluorescent nanomaterials have gained high relevance in biological applications as probes for various fluorescence-based spectroscopy and imaging techniques. Among these materials, dye-doped silica nanoparticles have demonstrated a high potential to overcome the limitations presented by conventional organic dyes such as high photobleaching, low stability and limited fluorescence intensity. In the present work we describe an effective approach for the preparation of fluorescent silica nanoparticles in the size range between 15 and 80 nm based on L-arginine-controlled hydrolysis of tetraethoxysilane in a biphasic cyclohexane–water system. Commercially available far-red fluorescent dyes (Atto647N, Abberior STAR 635, Dy-647, Dy-648 and Dy-649) were embedded covalently into the particle matrix, which was achieved by aminosilane coupling. The physical particle attributes (particle size, dispersion, degree of agglomeration and stability) and the fluorescence properties of the obtained particles were compared to particles from commonly known synthesis methods. As a result, the spectroscopic characteristics of the presented monodisperse dye-doped silica nanoparticles were similar to those of the free uncoupled dyes, but indicate a much higher photostability and brightness. As revealed by dynamic light scattering and ζ-potential measurements, all particle suspensions were stable in water and cell culture medium. In addition, uptake studies on A549 cells were performed, using confocal and stimulated emission depletion (STED) microscopy. Our approach allows for a step-by-step formation of dye-doped silica nanoparticles in the form of dye-incorporated spheres, which can be used as versatile fluorescent probes in confocal and STED imaging.

Solvent-free reversible deactivation radical polymerization of myrcene, a naturally occurring terpenoid monomer, with high regioselectivity was developed recently. Here, this green polymerization system is further improved to reach increased yields and produce polymers with high molar mass but still low dispersity and regioregular microstructure. To this end, two initiators (dibenzoyl peroxide, DBPO; azobis(isobutyronitrile), AIBN) at 65, 90, and 130 °C were applied, and it was demonstrated that these varying conditions have a huge effect not only on the monomer conversion and the molar mass of the product, but also on the microstructure of the resulting polymyrcene. The polymerizations utilized two trithiocarbonate chain-transfer agents, and were similar in yields, molar masses, and dispersity of the produced polymyrcene, but progressed differently for the diverse initiator–temperature pairs. Generally, in all systems, pseudo-first-order kinetics, linear increase of molar mass with conversion, and low Đ values were found as a result of controlled polymerization. The systems using AIBN and DBPO initiators at 90 and 130 °C, respectively, have rate constants of propagation (kpapp) lower than the decomposition rates (kd) of initiators, likewise important to control the polymerizations. At 130 °C, also branching occurred at the higher stage of the reaction, and lower regioregularity developed during the polymerization as a consequence of the favorable junction formation at elevated temperature and increased viscosity. Generally, compared to the previous study on the reversible deactivation radical polymerization of myrcene via reversible addition–fragmentation chain-transfer polymerization process, significantly higher conversions (30 → 65%) and increased chain length (9 → 40 kDa) were reached. The dispersity values for these polymerizations remained as low as 1.3–1.6, and also regioregular microstructures (up to 94%) were detected.

The tuning of wetting over an extreme range, from superhydrophilic to superhydrophobic, was demonstrated on 1D Al/Al2O3 nanostructures. While chaotic and tangled 1D Al/Al2O3 nanostructures exhibited complete wetting, they became water repellent (with a water contact angle (CA) [greater-than-or-equal]173[degree]) after the infiltration of poly[bis(2,2,2-trifluoroethoxy)phosphazene] (PTFEP) solution. This simple strategy allows the achievement of two extreme wetting regimes, perfect wetting and non-wetting, without altering the nanostructured surface topography. The same surface was also found to exhibit repellency towards artificial blood and hexadecane.

Double and triple network (TN) elastomers can be made by infusing monomers into a single network (SN) polymer, causing it to swell, and then polymerizing and cross-linking the monomers. The result is a double network (DN) elastomer in which one network is stretched and the other is in hydrostatic compression. TN systems are made by repeating the process starting with the DN material. The multinetwork (MN) elastomers exhibit a Mullins effect in which softening occurs upon a first cycle of loading, with the elastomer stiffness recovered above the previous maximum strain. The Mullins effect is attributed to rupture of the stretched network, eliminating the constraint on the compressed network, thereby motivating straining at the lower stiffness of the remaining material. A model for this process is developed, based on the previous work of Horgan et al. (2004, “A Theory of Stress Softening of Elastomers Based on Finite Chain Extensibility,” Proc. R. Soc. A, 460(2046), pp. 1737–1754). In the proposed model, a composite stiffness for the MN system is developed and a damage process introduced to degrade the contribution of the stretched network. The damage model is designed to account for the progressive elimination of chains that are most highly loaded in the stretched network, so that the undamaged stiffness is restored when the strain rises above levels previously experienced. The proposed model reproduces the behavior of the Mullins effect in the MN system.

The theoretical basis is developed for a strategy for enhancing the toughness of elastomers that have been damaged by the creation of a surface crack. The approach involves soaking the damaged elastomer for a limited time in a bath of the elastomer monomers, an ultra-violet initiator and cross-linkers to allow them all to diffuse into the specimen. The elastomer is then withdrawn from the bath at a stage where the diffusing species have only penetrated to a limited degree into the component, so that they are concentrated near its surface, including adjacent to the crack. Very soon thereafter the specimen is subjected to ultra-violet light, thereby causing the diffused species to polymerize and cross-link. As the diffusing monomers will have caused the elastomer to have swollen, the polymerization process will lock this volume expansion in place near the elastomer surface, and will have done so adjacent to the crack. Since a local expansion of the material around the crack and adjacent to its surfaces will reduce the energy release rate when the crack is forced to propagate, the swelling will have effectively toughened the elastomer against the growth of the pre-existing surface crack.

A viscoelastic constitutive law is developed for a hydrogel to encompass deviatoric deformations where the viscosity of the solvent contributes to the deviatoric stress of the system. The law is obtained in Kelvin–Voigt form by adding together the stress in the polymer network, the osmotic and solvent pressures and the viscous stress induced in the solvent. Transient behavior of the hydrogel is presented in terms of an example where transport of the solvent through the gel and viscosity due to deviatoric deformation interact to enable response that would otherwise be precluded, showing the significance of including the deviatoric viscosity. In addition, a simple relaxation problem is solved for a swollen hydrogel where volume of the hydrogel is preserved, namely small strain shear as induced in a rheometer.