Abstract:Toxicogenomics of iron oxide nanoparticles in the nematode C. elegansWe present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in C. elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposu… Show more
“…In fact, it is known that cytochrome P450 plays a role in the generation of oxidative stress . Furthermore, studies have shown the involvement of cytochrome P450 in the promotion of oxidative stress by NPs, including TiO 2 NPs . These findings suggest that there is possible increased oxidative stress in hESCs after TiO 2 NPs exposure.…”
The increasing number of nanoparticles (NPs) being used in various industries has led to growing concerns of potential hazards that NP exposure can incur on human health. However, its global effects on humans and the underlying mechanisms are not systemically studied. Human embryonic stem cells (hESCs), with the ability to differentiate to any cell types, provide a unique system to assess cellular, developmental, and functional toxicity in vitro within a single system highly relevant to human physiology. Here, the quantitative proteomics approach is adopted to evaluate the molecular consequences of titanium dioxide NPs (TiO NPs) exposure in hESCs. The study identifies ≈328 unique proteins significantly affected by TiO NPs exposure. Proteomics analysis highlights that TiO NPs can induce DNA damage, elevated oxidative stress, apoptotic responses, and cellular differentiation. Furthermore, in vivo analysis demonstrates remarkable reduction in the ability of hESCs in teratoma formation after TiO NPs exposure, suggesting impaired pluripotency. Subsequently, it is found that TiO NPs can disrupt hESC mesoderm differentiation into cardiomyocytes. The study unveils comprehensive changes in the molecular landscape of hESCs by TiO NPs and identifies the impact which TiO NPs can have on the pluripotency and differentiation properties of human stem cells.
“…In fact, it is known that cytochrome P450 plays a role in the generation of oxidative stress . Furthermore, studies have shown the involvement of cytochrome P450 in the promotion of oxidative stress by NPs, including TiO 2 NPs . These findings suggest that there is possible increased oxidative stress in hESCs after TiO 2 NPs exposure.…”
The increasing number of nanoparticles (NPs) being used in various industries has led to growing concerns of potential hazards that NP exposure can incur on human health. However, its global effects on humans and the underlying mechanisms are not systemically studied. Human embryonic stem cells (hESCs), with the ability to differentiate to any cell types, provide a unique system to assess cellular, developmental, and functional toxicity in vitro within a single system highly relevant to human physiology. Here, the quantitative proteomics approach is adopted to evaluate the molecular consequences of titanium dioxide NPs (TiO NPs) exposure in hESCs. The study identifies ≈328 unique proteins significantly affected by TiO NPs exposure. Proteomics analysis highlights that TiO NPs can induce DNA damage, elevated oxidative stress, apoptotic responses, and cellular differentiation. Furthermore, in vivo analysis demonstrates remarkable reduction in the ability of hESCs in teratoma formation after TiO NPs exposure, suggesting impaired pluripotency. Subsequently, it is found that TiO NPs can disrupt hESC mesoderm differentiation into cardiomyocytes. The study unveils comprehensive changes in the molecular landscape of hESCs by TiO NPs and identifies the impact which TiO NPs can have on the pluripotency and differentiation properties of human stem cells.
“…Due to sensitivity to environmental toxicants or stresses 4–6 , C . elegans has been widely used in toxicity assessment and toxicological study of various engineered nanomaterials (ENMs) 7–9 . Moreover, certain amount of miRNAs in response to ENMs, such as carbon-based ENMs, have been identified in nematodes 10,11 .…”
Exposure to graphene oxide (GO) induced some dysregulated microRNAs (miRNAs), such as the increase in
mir-247
, in nematode
Caenorhabditis elegans
. We here further identified
goa-1
encoding a Gαo and
pkc-1
encoding a serine/threonine protein kinase as the targets of neuronal
mir-247
in the regulation of GO toxicity. GO exposure increased the expressions of both GOA-1 and PKC-1. Mutation of
goa-1
or
pkc-1
induced a susceptibility to GO toxicity, and suppressed the resistance of
mir-247
mutant to GO toxicity. GOA-1 and PKC-1 could also act in the neurons to regulate the GO toxicity, and neuronal overexpression of
mir-247
could not affect the resistance of nematodes overexpressing neuronal
goa-1
or
pkc-1
lacking 3′-UTR to GO toxicity. In the neurons, GOA-1 acted upstream of diacylglycerol kinase/DGK-1 and PKC-1 to regulate the GO toxicity. Moreover, DGK-1 and GOA-1 functioned synergistically in the regulation of GO toxicity. Our results highlight the crucial role of neuronal Gαo signaling in response to GO in nematodes.
“…Figure 5E illustrates that both nanoformulations are capable to decrease the amount of executioner procaspase-3. Despite both, Dox and Elli are capable to induce oxidative stress and IONs presence could plausibly lead to a deregulation of metal homeostasis,30–32 no effect on the expression of MT-1/2 or MT-3 was found. Moreover, similar to free Dox, Dox@IONs-POES and Elli@IONs-PVP caused slight enhancement of p53 expression.Figure 5( A ) Representative micrographs of wound-healing assay showing the marked effect of Dox/Elli-tethered surface-modified IONs on a migration of tested cell lines.…”
BackgroundIron oxide nanoparticles (IONs) have been increasingly utilized in a wide spectrum of biomedical applications. Surface coatings of IONs can bestow a number of exceptional properties, including enhanced stability of IONs, increased loading of drugs or their controlled release.MethodsUsing two-step sonochemical protocol, IONs were surface-coated with polyoxyethylene stearate, polyvinylpyrrolidone or chitosan for a loading of two distinct topo II poisons (doxorubicin and ellipticine). The cytotoxic behavior was tested in vitro against breast cancer (MDA-MB-231) and healthy epithelial cells (HEK-293 and HBL-100). In addition, biocompatibility studies (hemotoxicity, protein corona formation, binding of third complement component) were performed.ResultsNotably, despite surface-coated IONs exhibited only negligible cytotoxicity, upon tethering with topo II poisons, synergistic or additional enhancement of cytotoxicity was found in MDA-MB-231 cells. Pronounced anti-migratory activity, DNA fragmentation, decrease in expression of procaspase-3 and enhancement of p53 expression were further identified upon exposure to surface-coated IONs with tethered doxorubicin and ellipticine. Moreover, surface-coated IONs nanoformulations of topo II poisons exhibited exceptional stability in human plasma with no protein corona and complement 3 binding, and only a mild induction of hemolysis in human red blood cells.ConclusionThe results imply a high potential of an efficient ultrasound-mediated surface functionalization of IONs as delivery vehicles to improve therapeutic efficiency of topo II poisons.
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