Iron Oxide Nanocubes as a New Certified Reference Material for Nanoparticle Size Measurements.

The rational design and increasing industrial use of nanomaterials require a reliable characterization of their physicochemical key properties like size, size distribution, shape, and surface chemistry. This calls for nanoscale reference materials (nanoRMs) for the validation and standardization of commonly used characterization methods closely matching real-world nonspherical nano-objects. This encouraged us to develop a nonspherical nanoRM of very small size consisting of 8 nm iron oxide nanocubes (BAM-N012) to complement spherical gold, silica, and polymer nanoRMs. In the following, the development and production of this nanoRM are highlighted including the characterization by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) as complementary methods for size and shape parameters, homogeneity and stability studies, and calculation of a complete uncertainty budget of the size features. The determination of the nanocubes' edge length by TEM and SAXS allows a method comparison. In addition, SAXS measurements can also provide the mean particle number density and the mass concentration. The certified size parameters, area equivalent circular diameter and square edge length, determined by TEM with a relative expanded uncertainty below 9%, are metrologically traceable to a natural constant for length, the very precisely known (111) lattice spacing of silicon. Cubic BAM-N012 qualifies as a certified nanoRM for estimating the precision and trueness, validation, and quality assurance of particle size and shape measurements with electron microscopy and SAXS as well as other sizing methods suitable for nanomaterials. The production of this new iron oxide nanocube RM presents an important achievement for the nanomaterial community, nanomaterial manufacturers, and regulators.

Handling (Nano)Silver as Antimicrobial Agent: Therapeutic Window, Dissolution Dynamics, Detection Methods and Molecular Interactions.

Silver is an antimicrobial agent well known since antiquity. With the emergence of multiresistant bacteria, it has come back into the focus of research, and ionic as well as nano-sized silver have been studied in vitro and in vivo. The results are controversial, silver being discussed as the "silver bullet" or a "wolf in sheep's clothing". A thorough search of literature from chemistry, materials and environmental science, biology and medicine led to this Review which summarizes the potential use of silver and its compounds in medicine, ongoing processes of dissolution and the different methods by which this usefulness can be evaluated. It also highlights the therapeutic window of silver, mechanistic interactions of silver and biological media as well as best practices for handling silver in a biomedical environment. This Review reflects the current knowhow and observations, and may thus give hints and guidelines to understand and interpret the observed effects.

Biomolecule-polymer hybrid compartments: combining the best of both worlds.

Compartmentalization is a fundamental principle in biology that is needed for the temporal and spatial separation of chemically incompatible reactions and biomolecules. Nano- or micro-sized compartments made of synthetic polymers are used to mimick this principle. The self-assembly of these polymers into vesicular objects is highly compatible with the integration of biomolecules, either into the lumen, the membrane or onto the surface of the vesicles. Thus, a great variety of biohybrid nano- and microscaled compartments has been developed exploiting the specific function and properties of targeting peptides, antibodies, enzymes, nucleic acids or lipids. Such biohybrid compartments have moved from simple systems encapsulating e.g. a model protein into complex multicompartmentalized structures that are able to combine the activity of different biomolecular cargos getting closer to the realization of artifical organelles or cells. Encapsulation of medically relevant cargos combined with careful design of the polymeric scaffold and specific surface functionalization have led to a significant progress in therapeutical applications such as targeted drug delivery or enzyme replacement therapy.

Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria.

BACKGROUND: Joint arthroplasty has improved the quality of life of patients worldwide, but infections of the prosthesis are frequent and cause significant morbidity. Antimicrobial coatings for implants promise to prevent these infections. METHODS: We have synthesized nanocapsules of titanium dioxide in amorphous or anatase form containing silver as antibacterial agent and tested their impact on bacterial growth. Furthermore, we explored the possible effect of the nanocapsules on the immune system. First, we studied their uptake into macrophages using a combination of electron microscopy and energy-dispersive spectroscopy. Second, we exposed immune cells to the nanocapsules and checked their activation state by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: Silver-containing titanium dioxide nanocapsules show strong antimicrobial activity against both E. coli and S. aureus and even against a multidrug-resistant strain of S. aureus. We could demonstrate the presence of the nanocapsules in macrophages, but, importantly, the nanocapsules did not affect cell viability and did not activate proinflammatory responses at doses up to 20 µg/mL. CONCLUSION: Our bactericidal silver-containing titanium dioxide nanocapsules fulfill important prerequisites for biomedical use and represent a promising material for the coating of artificial implants.

Synthesis and Applications of Nanocontainers and Nanorattles.

Nanorattles and hollow nanocontainers have unique properties related to the presence of a void space inside the shell, which has been shown to improve the properties of materials for e.g. catalysis, drug release, sensor materials or lithium ion batteries. This article summarizes our recent progress in the synthesis of hollow silica, titania and ceria nanorattles and nanocontainers, eventually encapsulating AgNPs as cargo and highlights their potential applications in catalysis and biomedicine.

Ag Nanoencapsulation for Antimicrobial Applications.

Biomaterial-related infections remain a significant challenge in medicine. Antimicrobial materials on the basis of Ag nanoparticles represent a promising solution for this issue. Therefore several Ag-containing nanocontainers and nanorattles have been synthesized and characterized that exhibit remarkable control over the release of Ag+ as antimicrobial active species. Their biological evaluation against prokaryotic as well as eukaryotic cells reveals that they fulfill the prerequisites for applications as antimicrobial implant coatings.

Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells.

The progression in the use of orthopedic implants has led to an increase in the absolute number of implant infections, triggering a search for more effective antibacterial coatings. Nanorattles have recently gained interest in biomedical applications such as drug delivery, as encapsulation of the cargo inside the hollow structure provides a physical protection from the surrounding environment. Here, silver-containing silica nanorattles (Ag@SiO2) were evaluated for their antimicrobial potential and for their impact on cells of the immune system. We show that Ag@SiO2 nanorattles exhibited a clear antibacterial effect against Escherichia coli as well as Staphylococcus aureus found in post-operative infections. Immunotoxicological analyses showed that the particles were taken up through an active phagocytic process by dendritic cells of the immune system and did not affect their viability nor induce unwanted immunological effects. Silver-containing silica nanorattles thus fulfill several prerequisites for an antibacterial coating on surgical implants.

Evidence of two-state reactivity in alkane hydroxylation by Lewis-acid bound copper-nitrene complexes.

The behavior of the Lewis-acid adducts of two copper-nitrene [Cu(NR)](+) complexes in nitrene-transfer and H-atom abstraction reactions have been demonstrated to depend on the nature of the nitrene substituents. Two-state reactivity, in which a singlet ground state and a nearby triplet excited-state both contribute, provides a useful model for interpreting reactivity trends of the two compounds.

Redox non-innocence of a N-heterocyclic nitrenium cation bound to a nickel-cyclam core.

The redox properties of Ni complexes bound to a new ligand, [DMC-nit](+), where a N-heterocyclic nitrenium group is anchored on a 1,4,8,11-tetraazacyclotetradecane backbone, have been examined using spectroscopic and DFT methods. Ligand-based [(DMC-nit)Ni](2+/+) reduction and metal-based [(DMC-nit)Ni](2+/3+) oxidation processes have been established for the [(DMC-nit)Ni](+/2+/3+) redox series, which represents the first examples of nitrenium nitrogen (N(nit))-bound first-row transition-metal complexes. An unprecedented bent binding mode of N(nit) in [(DMC-nit)Ni](2+) is observed, which possibly results from the absence of any N(nit)→Ni σ-donation. For the corresponding [(DMC-nit)Ni(F)](2+) complex, σ-donation is dominant, and hence a coplanar arrangement at N(nit) is predicted by DFT. The binding of the triazolium ion to Ni enables new chemistry (formate oxidation) that is not observed in a derivative that lacks this functional group. Thus the N-heterocyclic nitrenium ligand is a potentially useful and versatile reagent in transition-metal-based catalysis.