Nanoparticles

Toxicity studies of new nanomaterials designed for nanomedicine or other industrial applications

In recent year a large number of new nanomaterials for a wide range of applications have been introduced in the market. In the medicine, for example, nanoparticles are suggested as new diagnostic and therapeutic tools. At the same time, concerns exist about possible adverse health effects following human exposure to those nanomaterials. This research is focused on potential toxicity of several nanomaterials as amorphous and mesoporous silica, carbon soot, titanium oxide. Specifically, the damage to cells, DNA, proteins and lipid will be evaluated by in vitro citotoxicity screening, DNA single/double strand breaks, 8-OHdG (a biomarker of the oxidative stress of DNA) formation, denaturation, aggregation, fragmentation and oxidation of proteins, peroxidation of lipids.

 

Inorganic nanoparticles as enancher/carrier of active molecules

Nanoparticles of inorganic mesoporous materials, such as MCM-41 silica, represent new promising carriers for drug delivery, because they possess favourable characteristics and biocompatibility. Moreover the surface, both external and internal, can be functionalized by different organic groups to allow better control on drug loading and site-specific release.

The obtained host-guest complexes are tested about their physico-chemical properties and the activity of the included molecules is investigated by in vitro experiments, especially in order to verify the release and the skin accumulation.

 

Our bibliography on the subject

Peira et al., 2013 Influence of silica nanoparticles (SiO2-NP) on drug permeation (more...)

Peria et al., 2014 (doi: j.ijpharm.2014.03.052)

 

 

Role of soil fungi in the environmental fate of Engineered Nanoparticles

Engineered Nanoparticles (ENPs) may be released in the environment, either intentionally (i.e. as delivery systems in agriculture) or accidentally (i.e. erosion of ENPs-containing materials during use). Plants represent one of the routes of entrance of the ENPs in the food chain, increasing the risk of exposure of animals and humans. The majority of the higher plants, including many edible plants, can form mychorrizal symbiosis with fungi. These microorganisms are able to secrete different molecules, such as proteins and chelating acids, that may influence ENPs structure, chemistry and thus mobility in the soil and possible up-take by higher plants.
Research activities include a) investigation of whether and how mycorrhizal fungi can influence physico-chemical properties of some ENPs (ZnO, CuO, CdO, CdS, CdSO4), b) evaluation of the ENPs distribution in an in vitro culture with fungi, where they could remain in the extracellular compartment or be adsorbed onto or adsorbed into the hyphae, and c) evaluation of potential toxicity of ENPs on fungi, d) investigation of possible NPs absorption and translocation to the plant roots (by using an  in vitro mycorrhizal system).

 

Understanding the interaction between nano-TiO2 and skin

Extensive interdisciplinar research has been carried out to understand at the molecular level the interaction between nanometric TiO2 and skin. TiO2 is largely employed in cosmetics, but in vitro toxic effects have been reported when nano-TiO2 is exposed to UV light. A set of different TiO2 sample differentiated by crystal phase (rutile and anatase) or surface coating (naked, hydrophilic, hydrophobic) were employed. Our results suggest that positively charged anatase nano-TiO2, but not negatively charged rutile—, is strongly held on skin and able to promote a structural rearrangement of the lipid bilayer in the uppermost skin layer (stratum corneum). We observed that low amount of UV light (< 1 mW/m2) is sufficient to photoactivate the ROS production in anatase, but not in rutile, nano-TiO2 and induced oxidative damage on skin exposed to it. The present findings strongly encourage the use of rutile to produce safer TiO2-based cosmetic and pharmaceutical.

 

our bibliography on the subject

 

Turci et al., 2013 (DOI: 10.1021/tx400285j)

 

Embriotoxicity of nanoparticles

Studies focusing on the effects of nanoparticles exposure on reproductive system are still at the early stages. Recently Pietroiusti and coworkers reported that very low doses (from 10 ng to 30 μg/animal) of single walled carbon nanotubes (SWCNTs) administered to female mice soon after implantation caused miscarriages and fetal malformations. Simultaneously, Yamashita and coworkers published a study reporting that silica and titanium dioxide nanoparticles with diameters of 70 nm and 35 nm respectively, can cross the placenta barrier and cause pregnancy complications when injected intravenously (0.8 mg/mouse) into pregnant mice.

These studies suggest that the exposure to SWCNTs may represent a potential risk for pregnant women, especially in the occupational setting.

 

Our bibliography on the subject

 

Pietroiusti et al. 2012 DOI: 10.1039/c2nr11688j

 Pietroiusti et al. 2011 DOI: 10.1021/nn200372g

Yamashita et al. 2011  DOI: 10.1038/NNANO.2011.41 

 

 

Nanoparticles emitted by incinerator

Combustion process in incinerators usually generates fly ashes mainly made up by metal oxides, silica and carbon-based particles, often associated to metals. Physicochemical properties of the particles are influenced by many incinerator parameters. In collaboration with other Universities the Centre could prepare model solids of well defined chemical composition and particle size resembling the NP present in the emission of incinerators to evaluate their potential toxicity. Furthermore a study on the presence of nanoparticles in the environment and in some body compartments in the normal population may help to understand occupational and individual exposure to emitted NP.

 

Interaction between proteins and nanoparticles

The rapid development of nanotechnology has raised some concerns about the effects of engineered nanoparticles on human health and the environment. At the same time, NPs have attracted intense interest because of their potential applications in biomedicine. Hence, the requirement of a detailed knowledge of what takes place at the molecular level when nanoparticles get inside living organisms is a necessary step in assessing and likely predicting the nanoparticles toxicity/biocompatibility.

The elicited effects strongly depend on the early events occurring when NPs reach biological fluids, where the interaction with proteins is the primary process. Whereas the adsorption of proteins on biomaterials has been thoroughly investigated, the mechanisms underlying the interaction of proteins with nanoparticles are still largely unexplored.
A complete  picture of the proteins/nanoparticle interaction, taking into account  both thermodynamic and kinetic aspects, may be obtained only by integrating  different  techniques.

 

Our bibliography on the subject

 

Marucco et al 2013 (doi:10.1016/j.jcis.2013.12.025)

Fenoglio et al., 2011 (doi:10.1016/j.addr.2011.08.001)

Turci et al., 2010 (doi:10.1021/la904758j)

Fubini et al., 2010 (doi:10.3109/17435390.2010.509519)

 

 

 

Aggregation of silica nanoparticles and effect on silica toxicity

A well-defined silica nanoparticle model system was developed to study the effect of the size and structure of aggregates on their membranolytic activity. The aggregates were stable and characterized using transmission electron microscopy, dynamic light scattering, nitrogen adsorption, small-angle X-ray scattering, infrared spectroscopy, and electron paramagnetic resonance. Human red blood cells were used for assessing the membranolytic activity of aggregates. We found a decreasing hemolytic activity for increasing hydrodynamic diameter of the nanoparticle aggregates, in contrast to trends observed for isolated particles. We propose here a qualitative model that considers the fractal structure of the aggregates and its influence on membrane deformation to explain these observations. The open structure of the aggregates means that only a limited number of primary particles, from which the aggregates are built up, are in contact with the cell membrane. The adhesion energy is thus expected to decrease resulting in an overall lowered driving force for membrane deformation. Hence, the hemolytic activity of aggregates, following an excessive deformation of the cell membrane, decreases as the aggregate size increases. Our results indicate that the aggregate size and structure determine the hemolytic activity of silica nanoparticle aggregates.

 

Our bibliography on the subject

 

Thomassen et al, 2011 (doi:10.1021/tx2002178)

Translocation of titanium nanoparticles through the nervous system

Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health.

There are several pioneer studies reporting translocation of inhaled particulates to the brain trough a potential neuronal uptake mediated by the olfactory nerve. However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system (CNS) trough extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium and in the brain. To this purpose we used two different kind of nanoparticles: 1) titanium dioxide conjugated with the fluorescein isothiocyanate (FITC) and 2) carboxyl quantum dots as a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology. Intranasal treatments with nanoparticles were performed both subcronically for 5 days and acutely on adult CD1 mice. The olfactory epithelium and olfactory bulb were collected and analysed by confocal microscopy and ICP-AES at different survival time after treatment. Our results indicate that titanium dioxide nanoparticles delivered in the nose enter the brain. In vitro experiments on primary cultures of olfactory bulb neurons suggest that these cells are able to internalize nanoparticles, and ongoing studies are trying to characterize a possible toxic effects of these nanoparticles on olfactory neurons. We are also analysing their localization in the different cellular compartments of the olfactory epithelium. Data obtained following intranasal irrigation of quantum dots indicate that non neuronal compartments of the olfactory mucosa are preferentially involved in nanoparticles uptake, thus supporting the extracellular pathways as the most likely route to access the CNS. The possible selection of different penetration routes may be ascribed either at the different surface chemistry of the two kind of nanoparticles employed or to their difference in size and aggregation.

our bibliography on the subject

Garzotto et al. Symposium on Breakthroughs in Nanoparticles for Bio-Imaging. Roma-Avril 2010