Nanotoxicology

Toxicity of engineered nanoparticles

Nanosized particles have always been present in nature, but the accelerated penetration of engineered nanoparticles (ENP) in the market is raising serious concerns over their potential impact on the environment. A key aspect for the ecotoxicity assessment of ENP is the necessity of addressing their physicochemical behaviour in biologically-relevant media. The reason is that the environmental exposure is strongly dependent on adsorption and aggregation phenomena that may limit exposure but also promote local high concentrations in sediments or biofilms. Cerium oxide nanoparticles have a wide range of applications. They are used as additive in diesel fuel, but the commercial success of this application is limited, the main use of nanoceria being the formulation of slurries for the chemomechanical planarization (CMP) of silicon wafers in the production of integrated circuits. Their toxic effect has been linked to the production of harmful reactive oxygen species (ROS). Some works claim the effective uptake of nanoparticles by the cells but the toxicity of nanoceria is still not clear. Under similar conditions some authors report toxicity and other the absence of toxic effect or even a protection against oxidative processes. TEM images of algal cells exposed to 1.5 mg/L of CeO2 during 24 h clearly show damage in membrane (figure below). The disrupted cell wall appears separated from the cell membrane with plasma leaking into the vacuity. In parallel, a profusion of cytoplasmic vesicles can be observed as chloroplast and the rest of cell structures appear highly damaged. From Toxicol. Sci., 119, 135, 2011..

 

The redox chemistry of cerium oxide nanoparticles make them act also as inorganic antioxidant in biological systems. This behaviour depends on the presence of Ce3+ atoms accompanying oxygen vacancies on nanoparticle surface. Apart from the superoxidedismutase mimetic activity, catalase mimetic activity and the capacity to scavenge nitric oxide radicals, we have shown that cerium nanoparticles are capable scavenging the HOCl/ClO- system both in test tube and in vitro RAW cell culture model. The surface interaction involves the evolution of oxygen and the reduction of Ce4+ to Ce3+. The results are relevant because HOCl/ClO- is involved in tissue damage due to overstimulation of inflammatory processes. From RSD Adv., 5, 15613, 2016..

Toxicity and colloidal stability

The influence of aggregation on the bioactivity of engineered nanoparticles is as well-known fact. Despite the importance of the effects of aggregation in nanotoxicity, the influence of nanoparticles aggregation on the biological response remains unclear. Aggregation is a physical symptom of a more general physicochemical condition of colloidal particles, namely, colloidal stability. Colloidal stability is a global indicator of the tendency of a system to reduce its net surface energy, which may be achieved by homo- or hetero-aggregation, including location at bio-interfaces. Our reasearch on the role of colloidal stability as a driver of nanoparticle bioactivity explained the biological effect of nanoscaled zerovalent iron, nZVI. Colloidal stability is a fundamental driver of bioactivity, accounting for otherwise inexplicable differential biological effects. From Plos One, 9, e109645, 2014..

[The colloidal singularity prevents nZVI toxicity. Growth inhibition of P. subcapitata exposed to a linear nZVI dose gradient (0.025–5 mg/L). Typically, growth rate of control replicates was 1.4 d-1. The coefficient of variance for 72 h control cultures was 9%. Statistically significant differences (p,0.05) are marked by an asterisk. The concentration range in which the colloidal singularity occurred is shadowed.] From Plos One, 9, e109645, 2014..

Toxicity of polymeric nanoparticles

Dendrimers are hyperbranched polymeric, nanoscale molecules with exceptional properties that make them attractive for a variety of biomedical applications. They consist of a central core, from which radially branched monomers or dendrons grow in successive layers, called generations. Their nanostructure presents three main features from which their applications give raise. First, they are globular and highly symmetric as a result of which they possess an unusually low solution viscosity. Second, they have a large number of surface end-groups, which make them highly tunable in terms of solution chemistry. They also possess relatively large internal cavities allowing the encapsulation of smaller molecules. We have reported the toxic mechanisms of action of amine- and hydroxyl-terminated poly(amidoamine) dendrimers (PAMAM) towards a cyanobacterium of the genus Anabaena and the green alga Chlamydomonas reinhardtii. The cationic amino-terminated dendrimers significantly increased the formation of ROS in both organisms. Photosynthetic membranes and photosystem II photochemistry was not affected. Cell damage resulted in cytoplasm disorganization and cell deformities and was associated to an increase in ROS formation and lipid peroxidation in mitochondria in the green alga. Cell wall and membrane disruption with apparent loss of cytoplasmic contents was found in the cyanobacterium. We determined for the first time that cationic PAMAM dendrimers were quickly and largely internalized by both organisms. These results warn against the generalization of the use of dendrimers which may pose significant risk for the environment and particularly for primary producers which are determinant for the health of natural ecosystems. From Nanotoxicology, 9, 706, 2015..

[Representative confocal images of C. reinhardtii and Anabaena PCC7120 cells exposed to 1.5 mg/L of G2-NH2 PAMAM dendrimers showing cellular localization of BODIPY signal. Images are (left to right): bright field, chlorophyll fluorescence (red), BODIPY fluorescence (green) and overlay.] From Nanotoxicology, 9, 706, 2015.

Further reading

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Hypochlorite scavenging activity of cerium oxide nanoparticles, RSC Adv., 6, 62911-62915, 2016

Toxicological assessment of third generation (G3) poly(amidoamine) dendrimers using the Allium cepa test, Sci. Total Environ., 563–564, 899-903, 2016

Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states, Sci. Rep., 5, 15613, 2015

First evidences of PAMAM dendrimer internalization in microorganisms of environmental relevance: A linkage with toxicity and oxidative stress, Nanotoxicology, 9(6), 706-718, 2015

A colloidal singularity reveals the crucial role of colloidal stability for in vitro toxicity testing of nanomaterials, Plos One, 9(10) e109645, 2014

Fate and transformation products of amino terminated PAMAM dendrimers under ozonation and irradiation, J. Hazard. Mater., 266, 102–113, 2014

An insight into the mechanisms of nanoceria toxicity in photosynthetic organisms, Aquat. Toxicol., 122-123, 133-143, 2012

Physicochemical characterization and ecotoxicological assessment of CeO2 nanoparticles using two aquatic organisms, Toxicol. Sci., 119(1) 135-145, 2011