Abstract
BackgroundNanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits.ResultsIn this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg/ml). Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass/pH and activation of transcription factor-2 (ATF-2) were evaluated utilizing quantitative high content screening (HCS) approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg/ml.ConclusionsThe present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the combined analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.
Highlights
Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development
Confirmation of fluorescently labelled SiO2NP (30 nm and 400 nm) uptake by both THP-1 and A549 cell lines was observed by confocal microscopy after 24 h (Figure 1A, 1B)
Transmission electron microscopy (TEM) imaging clearly show the absence of significant aggregated clusters of 40 nm size alumina coated particles (Figure 1C) where particle size measurements have been included for clarity
Summary
Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Nanoparticles have received increasing attention for their potential applications in biology and medicine in recent years [1,2,3] Atmospheric particulates, such as diesel exhaust derivatives, have been recognized to have harmful effects on human health, including systemic and cardiovascular effects [4]. Lin et al [30] demonstrated in an in vitro study that amorphous SiO2NP (15 and 46 nm) significantly reduced the viability of human alveolar epithelial cells A549 in a dose- and time- dependent manner. They found that nanometre-sized SiO2NP inhibited DNA replication, transcription, and cell proliferation. Yu et al reported that amorphous silica nanoparticles below 100 nm did not induce any cytotoxicity measured by the mitochondrial viability assay [33]
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