Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO 2 -PDA have excellent colloidal stability in serum-supplemented culture media, even after long-term (24 h) exposure, showing no cytotoxic or genotoxic effects in vitro and ex vivo. Physiological responses, evaluated in vivo using Caenorhabditis elegans as the animal model, showed no impact on fertility and embryonic viability, induction of an oxidative stress response, and a mild impact on animal locomotion. These tests indicate that the synergistic combination of the silica matrix and PDA coating we developed effectively protects the SPIONs, providing enhanced colloidal stability and excellent biocompatibility.
The prevalence of allergic diseases is constantly increasing since few decades.Anthropogenic ultrafine particles (UFPs) and allergenic aerosols is highly involved in this increase; however, the underlying cellular mechanisms are not yet understood.Studies observing these effects focused mainly on singular in vivo or in vitro exposures of single particle sources, while there is only limited evidence on their subsequent or combined effects. Our study aimed at evaluating the effect of subsequent exposures to allergy-related anthropogenic and biogenic aerosols on cellular mechanism exposed at air-liquid interface (ALI) conditions. Bronchial epithelial BEAS-2B cells were exposed to UFP-rich combustion aerosols for 2 h with or without allergen pre-exposure to birch pollen extract (BPE) or house dust mite extract (HDME). The physicochemical properties of the generated particles were characterized by stateof-the-art analytical instrumentation. We evaluated the cellular response in terms of cytotoxicity, oxidative stress, genotoxicity, and in-depth gene expression profiling.We observed that single exposures with UFP, BPE, and HDME cause genotoxicity.Exposure to UFP induced pro-inflammatory canonical pathways, shifting to a more xenobiotic-related response with longer preincubation time. With additional allergen exposure, the modulation of pro-inflammatory and xenobiotic signaling was more pronounced and appeared faster. Moreover, aryl hydrocarbon receptor (AhR) signaling activation showed to be an important feature of UFP toxicity, which was especially pronounced upon pre-exposure. In summary, we were able to demonstrate the importance of subsequent exposure studies to understand realistic exposure situations and to identify possible adjuvant allergic effects and the underlying molecular mechanisms.
Especially through the release from anthropogenic sources, there is growing concern about human exposure to ultrafine particulate matter (UFP). Inhalation of UFP is associated with respiratory diseases such as asthma, pulmonary fibrosis and lung cancer, but their mechanisms of action are still vastly unknown. In this study we aimed to address the question whether the physical characteristics of UFP contribute most to their toxicity or whether the particles primarily act as carriers of toxic chemicals. For this scope, two distinct UFP aerosols with low or high content of semi-volatile organic compounds (SVOC) but comparable sizes were produced by a combustion aerosol standard soot generator and investigated regarding their acute (geno)-toxic potential in a cell model consisting of alveolar epithelial cells, macrophages, and fibroblasts at the air-liquid interface. Low SVOC UFP induced an increased cytotoxicity accompanied by a reduced cell number of epithelial cells and a decreased metabolic activity of fibroblasts. Furthermore, an increased intracellular release of reactive oxygen species (ROS) was observed after low SVOC UFP treatment, which resulted in a depletion of intracellular glutathione. The increased ROS release could be causative for the observed secondary genotoxicity in fibroblasts exclusively detected after exposure to low organic content UFP. High SVOC UFP did not impact cell viability, but an increased DNA damage could be detected in epithelial cells. All in all, UFP with low organic content seem to induce a stronger acute cytotoxic and oxidative stress response in epithelial cells, which might cause secondary effects in fibroblasts.
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