Jarosław Kaszewski

Biodegradation of the ZnO:Eu nanoparticles in the tissues of adult mouse after alimentary application

Biodegradable zinc oxide nanoparticles (ZnO NPs) are considered promising materials for future biomedical applications. To fulfil this potential, biodistribution and elimination patterns of ZnO NPs in the living organism need to be resolved. In order to investigate gastrointestinal absorption of ZnO NPs and their intra-organism distribution, water suspension of ZnO or fluorescent ZnO:Eu (Europium-doped zinc oxide) NPs (10mg/ml; 0.3ml/mouse) was alimentary-administered (IG: intra-gastric) to adult mice. Internal organs collected at key time-points after IG were evaluated by AAS for Zn concentration and analysed by cytometric techniques. We found that Zn-based NPs were readily absorbed and distributed (3 h post IG) in the nanoparticle form throughout the organism. Results suggest, that liver and kidneys were key organs responsible for NPs elimination, while accumulation was observed in the spleen and adipose tissues. We also showed that ZnO/ZnO:Eu NPs were able to cross majority of biological barriers in the organism (including blood-brain-barrier).

Impact of yttria stabilization on Tb3+ intra-shell luminescence efficiency in zirconium dioxide nanopowders

This paper reports the observation of Tb(3+) 4f-4f emission gain in ZrO2 nanocrystals stabilized by Y2O3 as the amount of stabilizer increases from 0% to 10% mol. The nanocrystals were obtained via microwave solvothermal technology. The photoluminescence properties of as-grown samples are investigated. The possibility of biological applications of the material is tested on living organisms (mice). The result indicates the potential use of the studied material as a luminescent nanomarker.

High Pressure Synthesis versus Calcination – Different Approaches to Crystallization of Zirconium Dioxide

Abstract Calcination and microwave-assisted hydrothermal processing of precipitated zirconium dioxide are compared. Characterization of synthesized products of these two technologies is presented. The infiuence of thermal treatment up to 1200oC on the structural and spectroscopic properties of the so-obtained zirconium dioxide is examined. It was found that initial crystallization of material inhibits the crystal growth up to the 800oC (by means of XRD and TEM techniques), while the material crystallized from amorphous hydroxide precursor at 400oC, exhibits 26 nm sized crystallites already. It was found using the TG technique that the temperature range 100–200oC during the calcination process is equivalent to a microwave hydrothermal process by means of water content. Mass loss is estimated to be about 18%. Based on X-ray investigations it was found that the initial hydroxide precursor is amorphous, however, its luminescence activity suggests the close range ordering in a material.

Reduction of Tb4+ ions in luminescent Y2O3:Tb nanorods prepared by microwave hydrothermal method

Abstract Terbium doped yttrium oxide was prepared with the microwave hydrothermal method. The Y 2 O 3 :Tb nanomaterial crystallized as needle-like grains. Bright luminescence in the green region was observed. Significant luminescence intensity increase was obtained after thermal treatment. Reduction of terbium ions was observed after heating in the air atmosphere. Tb 4+ ions were found to be stabilized by crystal impurities. Hydroxyl species were found to have impact on vacancies elimination. The terbium ions were used as optical and magnetic indicator of the material properties.

Rare earth doped nanoparticles of oxides for biomarkers applications

First generation of biomarkers (fluorescence labels) is based on organic dyes. To replace them nanoparticles (NPs)/quantum dots (QDs) of highly fluorescent CdTe-, CdS- and CdSe-based biomarkers were introduced. Despite the fact that these NPs show some advantageous properties, their use is limited by blinking, spectral diffusion of emission and use of cadmium, which should be avoided in the case of biological and medical applications. This fact motivated us to develop new generation of biomarkers using biocompatible oxides - ZnO, ZnAl2O4 and ZrO2. Their emission is activated by doping with rare earth (RE) ions.

Multimodal non-gadolinium oxide nanoparticles for MRI and fluorescence labelling

Magnetic Resonance Imaging (MRI) is considered a useful non-invasive method for cancer detection. However, MRI still has some limitations: low specificity for early-stage cancers as well as toxicity of Gadolinium ions, which were reported to accumulate in the nerve tissue and kidneys. Early cancer development and metastases monitoring are still difficult, because of the issues with permeability of contrasting agents through the blood-organ barriers. Nowadays, studies are being conducted to find the new contrasts with high magnetic moment, yet without gadolinium-induced toxicity. We propose an innovative, multimodal, high-k oxide-based contrasting nanoparticles (NPs), combining fluorescent properties of lanthanides with contrast in T1 and T2 spin relaxations. This material can facilitate both in-situ screening and visualization of tumour for fluorescence assisted biopsy or surgery. NPs used in our study were developed in the Institute of Physics, PAS. The NPs core was based on HfO2, doped with Eu ions, while Gd was used for positive control. Fluorescence was induced at 619nm, while emission was detectable at 630-650nm. The T1 and T2 relaxation times have been assessed using phantoms. Statistically significant changes were observed in T2 relaxation time. We used old rats, patients of the oncology clinic as an animal model. Prior to oral application of NPs (1mg/ml, 1ml/rat, LEC No 13/2015) the initial MRI screening of rats was performed. Weighted images T2 (3D FSE), SWI and SS-FSE were performed twice, 24 and 48 hours after IG. After imaging, tumours were surgically removed, for cytometric and pathomorphology evaluation.

Novel fluorescent oxides provide insight into the dynamics of nanoparticle mediated drug uptake from the gastro-intestinal tract

In recent years nanotechnology gathered much attention due to promising applications in biomedicine. Using nanoparticles as drug carriers could allow for more effective and efficient therapy in treating cancer or neurological diseases. This is due to their unique properties such as enhancement of drug bioavailability or the ability to protect the drug from degradation. In this study we performed in vivo (BALB-c mice) and in vitro (Caco-2 cell line) experiments with Y2O3:Tb_lectin conjugates as well as pure lectin to characterize the dynamics of nanoparticles mediated drug uptake from gastro-intestinal tract. Mice were given 0.3ml of Y2O3:Tb_lectin conjugates or pure lectin suspension and were sacrificed after 3h, 24h and 1 week (Y2O3:Tb_lectin conjugates) or 3h and 24h (pure lectin). Cell cultures were incubated for 24h with increasing concentration (0.001mg/ml; 0.01mg/ml; 0.1mg/ml; 1mg/ml) of Y2O3:Tb_lectin or pure lectin. After analysing gathered data we concluded that our nanoparticles successfully conjugated with lectin and allowed for its transport through physiological barriers. NPs_Lectin conjugates undergo absorption, distribution and redistribution similarly as free nanoparticles do, although it decreased the efficiency of absorption compared to free nanoparticles. Lastly after reaching the tissue conjugates dissolved leading to lectin deposition in the tissue.

Novel nanomaterials for applications in cancer imaging

Enormous potential of nanoparticles in medicine is a rapidly growing research field. Hereby, we focused on the applications of biocompatible oxide nanoparticles in the field of cancer diagnosis and therapy. This work was focused on the development of fluorescent Tb-doped ZrO2 nanoparticles (NPs) for application in lung cancer diagnostics. Obtained, hydrothermally created NPs were below 100 nm with very low influence of Tb concentration on size. Mice received suspension of nanoparticles (10 mg/ml, 0.3 ml/mouse) via gastric gavage. All protocols were according to the EU guidelines and approved by LEC agreements No 2/2012 and 13/2015. At 3h and 24h mice were sacrificed and all tissues collected for analyses under confocal microscope and scanning cytometry. Following oral administration, ZrO2:Tb nanoparticles were passively targeted to all tumour loci via the enhanced permeation and retention (EPR) effect. Due to the very tight endothelial barrier in the lungs NPs in this organ were targeted specifically to the areas of metastases rendering them a highly specific diagnostic tool for cancer diseases with high potential applications as a carrier of therapeutic factors.

Oxide-based materials by atomic layer deposition

Thin films of wide band-gap oxides grown by Atomic Layer Deposition (ALD) are suitable for a range of applications. Some of these applications will be presented. First of all, ALD-grown high-k HfO2 is used as a gate oxide in the electronic devices. Moreover, ALD-grown oxides can be used in memory devices, in transparent transistors, or as elements of solar cells. Regarding photovoltaics (PV), ALD-grown thin films of Al2O3 are already used as anti-reflection layers. In addition, thin films of ZnO are tested as replacement of ITO in PV devices. New applications in organic photovoltaics, electronics and optoelectronics are also demonstrated Considering new applications, the same layers, as used in electronics, can also find applications in biology, medicine and in a food industry. This is because layers of high-k oxides show antibacterial activity, as discussed in this work.

Imaging methods provide crucial understanding of the uptake and distribution processes of biodegradable ZnO doped Eu 3+ nanoparticles in living organism.

Oxide nanoparticles (NPs) doped with rare-earth ions are tested for applications as nanomarkers in biology. The aim of this study was to investigate the intra-organism distribution of ZnO nanoparticles doped with europium following gastric gavage (IG) in mice. The study is an example of the innovative and comprehensive methodology in research on biodistribution of nanomaterials in the body. We used quantitative (AAS) and imaging (scanning cytometry, confocal microscope) methods of assessing the distribution of rare-earth doped ZnO nanoparticles in the living organism. Visualization of these processes in the body was possible because of high fluorescence yield of europium. Imaging methods applied in this study (scanning cytometry and confocal microscopy) seem to be crucial for understanding the uptake and distribution patterns of nanoparticles within the living organism.