Nanotechnology as a new field of science is broadly exploited in a plethora of commercial uses. Biocompatible nanomaterials are also attractive for medical applications. However, an exact processes related with their biodistribution within the body needs to be examined. This study deals with future perspectives for biodegradable nanoparticle on the example of fluorescent ZnO NPs (zinc oxide nanoparticles), doped with europium (Eu) ions. The aim of the study was to evaluate distribution processes of biodegradable ZnO:Eu NPs within the living organism. ZnO:Eu NPs were administered intra-gastric (IG) (10 mg/ml, 0.3 ml/mouse) to adult Balb-c mice (n=35) and following 3h, 24h, 7d, 14d and 1m mice were sacrificed and internal organs were collected, as was described before [1]. For determination the excretion patterns of these nanostructure, ZnO NPs were orally administered to mice (n=24) with further measurement of zinc content in the feces of tested animals. All procedures were conducted according to local and EU regulations and approved by the LEC 44/2012. No pathological/behavioral changes were observed in mice. Biodegradable ZnO:Eu NPs revealed ability to overcome majority of physiological barriers in the organism, which renders them invaluable tool for biomedical applications. After 3h the presence of fluorescent NPs was already observed in key tissues and the peak of NPs distribution was observed at 24 h after IG in majority of tissues, including brain. Moreover, obtained results revealed fast and efficient clearance of ZnO NPs from the living organism, even following multiple administration of nanostructures (up to 4d after IG).
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.
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.
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.
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.
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