Fate and health impact of inorganic manufactured nanoparticles

Abstract

Inorganic nanoparticles (NPs) either based on metal oxides (iron oxide, cerium oxide, titanium dioxide, silicon dioxide, etc.) or metals (gold and silver) have now wide applications. Consequently it increases the probability of unintended exposure that could affect workers as well as the general population including susceptible people. Inhalation, ingestion, and dermal contact are the main routes of exposure. Before reaching the epithelial barrier lining the respiratory tract, the digestive tract, or the skin, NPs get in contact with biological fluids and become covered by molecules present in these fluids forming the so-called corona. The fate and the effects of NPs may be different according to the corona composition as the cell membrane does not interact directly with the NPs surface but with the NP surrounded by its corona. Endocytosis has been shown to be an important route of NPs uptake. However, the rate and mechanism of uptake seem to be cell-type dependent, cell density-dependent and vary for NPs of different size, charge, and other surface properties. Uptake is mostly an energy-dependent process, dependent on NPs size, shape, and charge. There is also some evidence of NPs exocytosis allowing NPs to cross epithelial barrier and enter systemic circulation. Different in vitro models have been proposed showing potential of different NPs to translocate. NPs biodistribution have been studied in different in vivo models after intravenous injection, oral ingestion, intratracheal instillation, or inhalation showing that smaller NPs can be better eliminated, but are also more widespread in secondary organs. Inhalation studies underline that NPs mainly remain at the site of exposure and only a low amount translocates. NPs health effects are widely studied. Toxicological studies performed on animals by intratracheal instillation have underlined that the most predominant effect of NPs is the induction of lung inflammation characterized by the increase of immune cells, frequently macrophages and neutrophils, in the bronchoalveolar lavage and the increased release of pro-inflammatory mediators (cytokines and chemokines), and all this effects are dependent on dose, size, surface reactivity, and NPs composition. There is also evidence of some cardiovascular and neurologic effects of NPs. NPs toxicity mainly results from their ability to induce an oxidative stress resulting from the ability of NPs to directly or indirectly generate reactive oxygen species (ROS). Some studies have shown the role of specific interactions between NPs and proteins in cell activation or cell metabolism suggesting potential additional pathways of toxicity independent of oxidative stress. A better knowledge about the NPs properties involved in their toxicity is expected in order to propose NPs safe by design.