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Nanopartikel (NP) werden insbesondere bei Herstellungs- und Verarbeitungsprozessen in nanotechnologischen Betrieben in die Umgebungsluft freigesetzt und vornehmlich via Inhalation in den menschlichen Organismus aufgenommen. Aufgrund ihrer Größe und veränderter physikochemischer Eigenschaften stellen NP ein bisher nicht genügend einschätzbares Gesundheitsrisiko dar. Daher steht die Interaktion aspirierter NP mit dem Lungengewebe im Fokus nanotoxikologischer Untersuchungen. Die Effekte aerogener NP wurden sowohl in vivo mittels Inhalation und Instillation als auch in vitro in Zellkultursystemen eingehend untersucht. Als Hauptmechanismus der toxischen Effekte wird dabei die NP-induzierte Bildung reaktiver Sauerstoffagenzien postuliert. Der resultierende oxidative Stress ist in der Lage, zelluläre Bestandteile wie Membrane, Proteine, DNA und Organellen zu schädigen und infolgedessen Entzündungsprozesse und Zelltod auszulösen. Diesbezüglich erfordern die Fortschritte der Nanotechnologie, die mit einem zunehmenden Umgang des Menschen mit NP einhergehen, eine entsprechende Risikobewertung. Aufgrund von fehlender Standardisierung sowie von Unterschieden in der Dosimetrie und den Messverfahren konnten die Wirkmechanismen der NP bislang nicht vollständig aufgeklärt werden. Zudem stehen die Ergebnisse von Hochdosis-Akutstudien wegen der unrealistischen Belastung in der Kritik. Aus diesem Grund war ein Ziel der vorliegenden Arbeit, eine realitätsnahe Bewertung des Risikopotenzials der PSLT-NP TiO2 und BaSO4 nach Langzeitexposition zu geringen Dosen in vitro zu ermitteln. Als weiteres Ziel soll das dazu etablierte Modell die Aussagekraft von In vitro-Studien erhöhen, um eine einfache und reproduzierbare Prognose von adversen biologischen Effekten in vivo zu erreichen und somit Tierversuche zu reduzieren. Das Modell wurde auf Basis von In vivo-Langzeitstudien mit niedriger Dosis auf höchstem europäischen Standard etabliert und soll die chronische Exposition von Angestellten gegen

In this work, we demonstrate that cutting diamond crystals with a laser (532 nm wavelength, 0.5 mJ energy, 200 ns pulse duration at 15 kHz) produced a ≲20 nm thick surface layer with magnetic order at room temperature. We measured the magnetic moment of five natural and six CVD diamond crystals of different sizes, nitrogen contents and surface orientations with a SQUID magnetometer. A robust ferromagnetic response at 300 K was observed only for crystals that were cut with the laser along the (100) surface orientation. The magnetic signals were much weaker for the (110) and negligible for the (111) orientations. We attribute the magnetic order to the disordered graphite layer produced by the laser at the diamond surface. The ferromagnetic signal vanished after chemical etching or after moderate temperature annealing. The obtained results indicate that laser treatment of diamond may pave the way to create ferromagnetic spots at its surface.

In-depth characterization has introduced new molecular subtypes of gastric cancer (GC). To identify these, new approaches and techniques are required. Liquid biopsies are trendsetting and provide an easy and feasible method to identify and to monitor GC patients. In a prospective cohort of 87 GC patients, extracellular vesicles (EVs) were isolated from 250 µL of plasma. The total RNA was isolated with TRIZOL. The total RNA amount and the relative mRNA levels of CD44, PTEN, and FASN were measured by qRT-PCR. The isolation of EVs and their contained mRNA was possible in all 87 samples investigated. The relative mRNA levels of PTEN were higher in patients already treated by chemotherapy than in chemo-naïve patients. In patients who had undergone neoadjuvant chemotherapy followed by gastrectomy, a decrease in the total RNA amount was observed after neoadjuvant chemotherapy and gastrectomy, while FASN and CD44 mRNA levels decreased only after gastrectomy. The amount of RNA and the relative mRNA levels of FASN and CD44 in EVs were affected more significantly by chemotherapy and gastrectomy than by chemotherapy alone. Therefore, they are a potential biomarker for monitoring treatment response. Future analyses are needed to identify GC-specific key RNAs in EVs, which could be used for the diagnosis of gastric cancer patients in order to determine their molecular subtype and to accompany the therapeutic response.

Useful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper.

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]) with hydrodynamic diameter of 37.8 0.5 nm, core diameter of 19.2 1.4 nm and -potential of 18.0 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4] could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]. Conclusions