Nanoengineered silica: Properties, applications and toxicity

Mebert, Andrea Mathilde; Baglole, Carolyn J.; Desimone, Martín Federico; Maysinger, Dušica

doi:10.1016/j.fct.2017.05.054

Cited by 157 publications

(86 citation statements)

References 237 publications

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“…Nowadays, nanotechnology environmental health and safety is required to have better understanding of toxicological responses of engineered nanomaterials in living organisms, since it is beneficial for the design strategy of safe nanotechnique-based diagnostics or therapeutics. 23 This study was built on our previous work to elaborate on hepatic lipid metabolism disturbed by SiNPs in vivo and in vitro. For the first time, we reveal that the TLR5-signaling pathway is responsible for impaired hepatic lipid metabolism induced by SiNPs.…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

Duan¹,

Liang²,

Lin³

et al. 2018

IJN

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BackgroundAs a promising nanocarrier in biomedical fields, silica nanoparticles (SiNPs) could transfer from the circulatory system to multiple organs. Among these, blood–liver molecular exchange is a critical factor in biological response to NPs. However, the potential effect of SiNPs on hepatic lipid metabolism is unclear. In this study, we employed three models to attempt discover whether and how SiNPs disturb hepatic lipid metabolism in vivo and in vitro.MethodsFirstly we used ICR mice models to evaulated the effects of SiNPs on the serum and hepatic lipid levels through repeated intravenous administration, meanwhile, the protein expressions of protein markers of lipogenesis (ACC1 and FAS), the key enzyme of fatty acid β-oxidation, CPT1A,and leptin levels in liver were detected by western blot. For verification studies, the model organism zebrafish and cultured hepatic L02 cells were further performed. The TLR5 and adipocytokine-signaling pathway were verified.ResultsInflammatory cell infiltration and mild steatosis induced by SiNPs were observed in the liver. Cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were elevated significantly in both blood serum and liver tissue, whereas the ratio of high-density:low-density lipoprotein cholesterol was markedly decreased. Protein markers of lipogenesis (ACC1 and FAS) were elevated significantly in liver tissue, whereas the key enzyme of fatty acid β-oxidation, CPT1A, was decreased significantly. Interestingly, leptin levels in the SiNP-treated group were also elevated markedly. In addition, SiNPs caused hepatic damage and steatosis in zebrafish and enhanced hyperlipemia in high-cholesterol diet zebrafish. Similarly, SiNPs increased the release of inflammatory cytokines (IL1β, IL6, IL8, and TNFα) and activated the TLR5-signaling pathway in hepatic L02 cells.ConclusionIn summary, our study found that SiNPs triggered hyperlipemia and hepatic steatosis via the TLR5-signaling pathway. This suggests that regulation of TLR5 could be a novel therapeutic target to reduce side effects of NPs in living organisms.

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Section: Discussionmentioning

confidence: 99%

Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

Duan¹,

Liang²,

Lin³

et al. 2018

IJN

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“…In recent decades, the use of nanotechnology has increased in many industrial applications [ 1 ]. Among different nanomaterials (i.e., materials with any external dimensions in the nanoscale, 1–100 nm) [ 2 ], silica (SiO 2 ) nanoparticles (NPs) have attracted considerable attention in various applications due to their appealing physicochemical properties [ 3 , 4 ]. Based on the structure defined by X-ray-diffraction spectroscopy [ 5 ], there are two main forms of silica: amorphous and crystalline.…”

Section: Introductionmentioning

confidence: 99%

Increased Uptake of Silica Nanoparticles in Inflamed Macrophages but Not upon Co-Exposure to Micron-Sized Particles

Sušnik

Taladriz‐Blanco

Drašler

et al. 2020

Cells

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Silica nanoparticles (NPs) are widely used in various industrial and biomedical applications. Little is known about the cellular uptake of co-exposed silica particles, as can be expected in our daily life. In addition, an inflamed microenvironment might affect a NP’s uptake and a cell’s physiological response. Herein, prestimulated mouse J774A.1 macrophages with bacterial lipopolysaccharide were post-exposed to micron- and nanosized silica particles, either alone or together, i.e., simultaneously or sequentially, for different time points. The results indicated a morphological change and increased expression of tumor necrosis factor alpha in lipopolysaccharide prestimulated cells, suggesting a M1-polarization phenotype. Confocal laser scanning microscopy revealed the intracellular accumulation and uptake of both particle types for all exposure conditions. A flow cytometry analysis showed an increased particle uptake in lipopolysaccharide prestimulated macrophages. However, no differences were observed in particle uptakes between single- and co-exposure conditions. We did not observe any colocalization between the two silica (SiO2) particles. However, there was a positive colocalization between lysosomes and nanosized silica but only a few colocalized events with micro-sized silica particles. This suggests differential intracellular localizations of silica particles in macrophages and a possible activation of distinct endocytic pathways. The results demonstrate that the cellular uptake of NPs is modulated in inflamed macrophages but not in the presence of micron-sized particles.

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“…Silica nanoparticles (SiNPs) are one of the most widely used engineered nanomaterials. SiNPs with favorable properties (biocompatibility and biodegradability) have been widely exploited in the cosmetics, food, and pharmaceutical industries and in the biomedical fields [15][16][17][18]. With the widespread prevalence of SiNPs, potential dermal, oral, or intranasal exposure chances have increased.…”

Section: Introductionmentioning

confidence: 99%

Silica nanoparticles induce autophagosome accumulation via activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes

Duan

et al. 2018

Autophagy

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Autophagy dysfunction is a potential toxic effect of nanoparticles. Previous studies have indicated that silica nanoparticles (SiNPs) induce macroautophagy/autophagy dysfunction, while the precise mechanisms remain uncertain. Hence, the present study investigated the molecular mechanisms by which SiNPs enhanced autophagosome synthesis, which then contributed to autophagy dysfunction. First, the effects of SiNPs on autophagy and autophagic flux were verified using transmission electron microscopy, laser scanning confocal microscopy, and western blot assays. Then, the activation of endoplasmic reticular (ER) stress was validated to be through the EIF2AK3 and ATF6 UPR pathways but not the ERN1-XBP1 pathway, along with the upregulation of downstream ATF4 and DDIT3. Thereafter, the ER stress inhibitor 4-phenylbutyrate (4-PBA) was used to verify that SiNP-induced autophagy could be influenced by ER stress. Furthermore, specialized lentiviral shRNA were employed to determine that autophagy was induced via specific activation of the EIF2AK3 and ATF6 UPR pathways. Finally, the 2 autophagic genes LC3B and ATG12 were found to be transcriptionally upregulated by downstream ATF4 and DDIT3 in ER stress, which contributed to the SiNP-enhanced autophagosome synthesis. Taken together, these data suggest that SiNPs induced autophagosome accumulation via the activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes, which offers a new insight into detailed molecular mechanisms underlying SiNP-induced autophagy dysfunction, and specifically how UPR pathways regulate key autophagic genes. This work provides novel evidence for the study of toxic effects and risk assessment of SiNPs.

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Nanoengineered silica: Properties, applications and toxicity

Cited by 157 publications

References 237 publications

Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro

Increased Uptake of Silica Nanoparticles in Inflamed Macrophages but Not upon Co-Exposure to Micron-Sized Particles

Silica nanoparticles induce autophagosome accumulation via activation of the EIF2AK3 and ATF6 UPR pathways in hepatocytes

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