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Diffusely dispersed metal and metal oxide nanoparticles (NPs) can adversely affect living organisms through various mechanisms and exposure routes. One mechanism behind their toxic potency is their ability to generate reactive oxygen species (ROS) directly or indirectly to an extent that depends on the dose, metal speciation, and exposure route. This review provides an overview of the mechanisms of ROS formation associated with metal and metal oxide NPs and proposes a possible way forward for their future categorization. Metal and metal oxide NPs can form ROS via processes related to corrosion, photochemistry, and surface defects, as well as via Fenton, Fenton-like, and Haber–Weiss reactions. Regular ligands such as biomolecules can interact with metallic NP surfaces and influence their properties and thus their capabilities of generating ROS by changing characteristics such as surface charge, surface composition, dissolution behavior, and colloidal stability. Interactions between metallic NPs and cells and their organelles can indirectly induce ROS formation via different biological responses. H2O2 can also be generated by a cell due to inflammation, induced by interactions with metallic NPs or released metal species that can initiate Fenton(-like) and Haber–Weiss reactions forming various radicals. This review discusses these different pathways and, in addition, nano-specific aspects such as shifts in the band gaps of metal oxides and how these shifts at biologically relevant energies (similar to activation energies of biological reactions) can be linked to ROS production and indicate which radical species forms. The influences of kinetic aspects, interactions with biomolecules, solution chemistry (e.g., Cl− and pH), and NP characteristics (e.g., size and surface defects) on ROS mechanisms and formation are discussed. Categorization via four tiers is suggested as a way forward to group metal and metal oxide NPs based on the ROS reaction pathways that they may undergo, an approach that does not include kinetics or environmental variations. The criteria for the four tiers are based on the ability of the metallic NPs to induce Fenton(-like) and Haber–Weiss reactions, corrode, and interact with biomolecules and their surface catalytic properties. The importance of considering kinetic data to improve the proposed categorization is highlighted. [ABSTRACT FROM AUTHOR]

Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1β release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale® system, and NPs were deposited on the co-culture using XposeALI®. No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1) were observed after exposure of the co-culture in ALI (max 5 µg/cm2) or submerged (max 22 µg/cm2) conditions. In contrast, CeO2 NPs cause clear IL-1β release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions. [ABSTRACT FROM AUTHOR]

The increased use of nanoparticles (NPs) requires efficient testing of their potential toxic effects. A promising approach is to use reporter cell lines to quickly assess the activation of cellular stress response pathways. This study aimed to use the ToxTracker reporter cell lines to investigate (geno)toxicity of various metal- or metal oxide NPs and draw general conclusions on NP-induced effects, in combination with our previous findings. The NPs tested in this study (n = 18) also included quantum dots (QDs) in different sizes. The results showed a large variation in cytotoxicity of the NPs tested. Furthermore, whereas many induced oxidative stress only few activated reporters related to DNA damage. NPs of manganese (Mn and Mn3O4) induced the most remarkable ToxTracker response with activation of reporters for oxidative stress, DNA damage, protein unfolding and p53-related stress. The QDs (CdTe) were highly toxic showing clearly size-dependent effects and calculations suggest surface area as the most relevant dose metric. Of all NPs investigated in this and previous studies the following induce the DNA damage reporter; CuO, Co, CoO, CdTe QDs, Mn, Mn3O4, V2O5, and welding NPs. We suggest that these NPs are of particular concern when considering genotoxicity induced by metal- and metal oxide NPs. [ABSTRACT FROM AUTHOR]