HINAMOX

"Health Impact of Engineered Metal and Metal Oxide Nanoparticles: Response, Bioimaging and Distribution at Cellular and Body Level"

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 Obiettivo del progetto (Objective)

'Metal oxide and metal NPs are particularly dangerous for two reasons: their special catalytic activity coming from the properties of their nanointerface may interfere with numerous intracellular biochemical processes and the decomposition of NPs and the ion leakage could heavily interfere with the intracellular free metal ion homeostasis, which is essential for cell metabolism. A very specific problem is the difficulty of localizing and quantifying them in cells. Obtaining dose effect relationships is not simple, because of the unknown amount of material present in affected cells. The following main points will be addressed in this proposal:1) Design and synthesis of metal oxide and metal NPs, which can be traced by SPECT, PET, and fluorescence techniques and the appropriate characterization of these NPs.2) Application of label-free techniques, such as IBM and EM to ensure that the radioactive and fluorescent constituents do not modify the cytological and organismic response by themselves.3) Characterization of the uptake, distribution kinetics and NP release at the level of the organism.4) Study of the interaction of NPs with plasma components forming complexes with NPs and the assessment of their possible impact on the uptake compared with that of bare or capped particles.5) Quantification and localization of metallic NPs in immune competent cells is a key task for the establishment of proper dose-response correlations. A technique applicable with living cells as ultimate control will be IBM, capable of detecting single metal NPs in cells at different depths.6) Development of sophisticated cell physiological approaches focusing on the determination of oxidative activity, cytokine production and adaptive processes concerning signalling pathways beyond standard vitality tests. The research project will indicate toxic levels of various NPs and sub-toxic effects will be investigated by analysing the signalling response of immune cells'

Introduzione (Teaser)

Metal oxide and metal nanoparticles are used in various industrial processes and commonly used products, from sun creams to electronic devices and fuels. A European study investigated the health effects on exposure to a range of nanoparticles.

Descrizione progetto (Article)

Scientists fear that metal and metal oxide nanoparticles may be potentially hazardous due to the special catalytic activity arising as a result of the properties at the nano interface. Additionally, their decomposition may lead to an increase in intracellular ion concentration and interfere with cell metabolism.

A very specific problem in dealing with the toxicological evaluation of nanomaterials, and in particular with metal oxide nanoparticles, is the difficulty of localising and quantifying them in cells and organs. To this end, the EU-funded HINAMOX project synthesised specifically labelled nanoparticles for use in in vitro cell assays to trace their biodistribution.

Radiolabelled metal and metal oxide nanoparticles were generated that could be traced by positron emission tomography (PET) and single photon emission computed tomography (SPECT). Fluorescently labelled particles were also designed and used for uptake studies in vitro.

The intracellular fate of these particles is dependent on their characteristics, surface chemistry, and interaction with proteins and other biologically relevant molecules. To study nanoparticle processing within cells, partners applied confocal Raman microscopy, transmission electron microscopy (TEM), ion beam microscopy (IBM) and confocal laser scanning microscopy.

In vitro culture of nanoparticles with cells revealed that internalisation required at least 12 hours. Uptake was hindered by the presence of protein coronas on the nanoparticle surface and confocal microscopy of fluorescently labelled nanoparticles showed an internalisation pattern that correlated with endosome/lysosome uptake.

Scientists also studied the cytotoxicity, immunological impact and oxidative stress effect of metal nanoparticles on macrophages, alveolar epithelial type two (ATII) cells and lung epithelial cells. This analysis was of high physiological relevance as lung inhalation constitutes the most likely route of nanoparticle exposure.

In vivo biodistribution PET analysis following intravenous administration of nanoparticles unveiled a strong size dependency of the distribution and accumulation of nanoparticles in all organs. However, a negligible accumulation of nanoparticles was observed in the brain irrespective of size.

The results of the HINAMOX study, combined with field measurements to assess nanoparticle emission during powder production, attest to health hazards posed by these novel materials. The outcomes of the study should provide a basis for the formulation of new health and safety procedures to minimise exposure to nanoparticles.