Biological Responses to Engineered Nanomaterials: Needs for the Next Decade.
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ABSTRACT:
SUBMITTER: Murphy CJ
PROVIDER: S-EPMC4827556 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
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Project description:The potential environmental impact of nanomaterials is a critical concern and the ability to assess these potential impacts is top priority for the progress of sustainable nanotechnology. Risk assessment tools are needed to enable decision makers to rapidly assess the potential risks that may be imposed by engineered nanomaterials (ENMs), particularly when confronted by the reality of limited hazard or exposure data. In this review, we examine a range of available risk assessment frameworks considering the contexts in which different stakeholders may need to assess the potential environmental impacts of ENMs. Assessment frameworks and tools that are suitable for the different decision analysis scenarios are then identified. In addition, we identify the gaps that currently exist between the needs of decision makers, for a range of decision scenarios, and the abilities of present frameworks and tools to meet those needs.
| S-EPMC5433198 | biostudies-literature
Project description:BACKGROUND:Engineered nanomaterials (ENM) are used extensively in food products to fulfill a number of roles, including enhancement of color and texture, for nutritional fortification, enhanced bioavailability, improved barrier properties of packaging, and enhanced food preservation. Safety assessment of ingested engineered nanomaterials (iENM) has gained interest in the nanotoxicology community in recent years. A variety of test systems and approaches have been used for such evaluations, with in vitro monoculture cell models being the most common test systems, owing to their low cost and ease-of-use. The goal of this review is to systematically assess the current state of science in toxicological testing of iENM, with particular emphasis on model test systems, their physiological relevance, methodological strengths and challenges, realistic doses (ranges and rates), and then to identify future research needs and priorities based on these assessments. METHODS:Extensive searches were conducted in Google Scholar, PubMed and Web of Science to identify peer-reviewed literature on safety assessment of iENM over the last decade, using keywords such as "nanoparticle", "food", "toxicity", and combinations thereof. Relevant literature was assessed based on a set of criteria that included the relevance of nanomaterials tested; ENM physicochemical and morphological characterization; dispersion and dosimetry in an in vitro system; dose ranges employed, the rationale and dose realism; dissolution behavior of iENM; endpoints tested, and the main findings of each study. Observations were entered into an excel spreadsheet, transferred to Origin, from where summary statistics were calculated to assess patterns, trends, and research gaps. RESULTS:A total of 650 peer-reviewed publications were identified from 2007 to 2017, of which 39 were deemed relevant. Only 21% of the studies used food grade nanomaterials for testing; adequate physicochemical and morphological characterization was performed in 53% of the studies. All in vitro studies lacked dosimetry and 60% of them did not provide a rationale for the doses tested and their relevance. Only 12% of the studies attempted to consider the dissolution kinetics of nanomaterials. Moreover, only 1 study attempted to prepare and characterize standardized nanoparticle dispersions. CONCLUSION:We identified 5 clusters of factors deemed relevant to nanotoxicology of food-grade iENM: (i) using food-grade nanomaterials for toxicity testing; (ii) performing comprehensive physicochemical and morphological characterization of iENM in the dry state, (iii) establishing standard NP dispersions and their characterization in cell culture medium, (iv) employing realistic dose ranges and standardized in vitro dosimetry models, and (v) investigating dissolution kinetics and biotransformation behavior of iENM in synthetic media representative of the gastrointestinal (GI) tract fluids, including analyses in a fasted state and in the presence of a food matrix. We discussed how these factors, when not considered thoughtfully, could influence the results and generalizability of in vitro and in vivo testing. We conclude with a set of recommendations to guide future iENM toxicity studies and to develop/adopt more relevant in vitro model systems representative of in vivo animal and human iENM exposure scenarios.
| S-EPMC6029122 | biostudies-literature
Project description:Traditional tissue regeneration approaches to activate cell behaviors on biomaterials rely on the use of extracellular-matrix-based or soluble growth-factor cues. In this article, a novel approach is highlighted to dynamically steer cellular phenomena such as cell motility based on nanoscale substratum features of biological ligands. Albumin-derived nanocarriers (ANCs) with variable nanoscale-size features are functionalized with fibronectin III9-10 matrix ligands, and their effects on primary human keratinocyte activation are investigated. The presentation of fibronectin fragments from ANCs significantly enhances cell migration as compared to free ligands at equivalent concentrations. Notably, cell migration is influenced by the size of the underlying ANCs even for variably sized ANCs covered in comparable levels of fibronectin fragment. For equivalent ligand concentrations, cell migration on the smaller-sized ANCs (30 and 50 nm) is significantly enhanced as compared to that on larger-sized ANCs (75 and 100 nm). In contrast, the enhancement of cell migration on nanocarriers is abolished by the use of immobilized, biofunctionalized ANCs, indicating that "dynamic" nanocarrier internalization events underlie the role of nanocarrier geometry on the differential regulation of cell migration kinetics. Uptake studies using fluorescent ANCs indicate that larger-sized ANCs cause delayed endocytic kinetics and hence could present barriers for internalization during the cell adhesion and motility processes. Motile cells exhibit diminished migration upon exposure to clathrin inhibitors, but not caveolin inhibitors, suggesting the role of clathrin-mediated endocytosis in facilitating cell migratory responsiveness to the nanocarriers. Overall, a monotonic relationship is found between the nanocarrier cytointernalization rate and the cell migration rate, suggesting the possibility of designing biointerfacial features for the dynamic control of cell migration. Thus, the functionalization of a mobile nanocarrier by a biorelevant ligand can be used to sensitize cellular motility activation to the adhesion ligands, and such nanocarrier interfaces can dynamically attune cell migration kinetics by modulating the uptake of the ligand-nanocarrier complex via nanocarrier size.
| S-EPMC3335745 | biostudies-literature
Project description:C57BL/6 mice were exposed by oropharyngeal aspiration to 28 nanomaterials including different surface functionalizations on 4 concecutive days with the dose of 10ug/day. Total RNA was collected from the mice lung biopsies after sacrificing.
2021-05-26 | GSE157266 | GEO
Project description:BackgroundEngineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity.MethodsFour laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment.ResultsTiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice.ConclusionsENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.
| S-EPMC3672912 | biostudies-literature
Project description:Traditionally engineered genetic circuits have almost exclusively used naturally occurring transcriptional repressors. Recently, non-natural transcription factors (repressors) have been engineered and employed in synthetic biology with great success. However, transcriptional anti-repressors have largely been absent with regard to the regulation of genes in engineered genetic circuits. Here, we present a workflow for engineering systems of non-natural anti-repressors. In this study, we create 41 inducible anti-repressors. This collection of transcription factors respond to two distinct ligands, fructose (anti-FruR) or D-ribose (anti-RbsR); and were complemented by 14 additional engineered anti-repressors that respond to the ligand isopropyl β-d-1-thiogalactopyranoside (anti-LacI). In turn, we use this collection of anti-repressors and complementary genetic architectures to confer logical control over gene expression. Here, we achieved all NOT oriented logical controls (i.e., NOT, NOR, NAND, and XNOR). The engineered transcription factors and corresponding series, parallel, and series-parallel genetic architectures represent a nascent anti-repressor based transcriptional programming structure.
| S-EPMC7477573 | biostudies-literature
Project description:BACKGROUND:The increasing use of engineered nanomaterials (ENMs) of varying physical and chemical characteristics poses a great challenge for screening and assessing the potential pathology induced by these materials, necessitating novel toxicological approaches. Toxicogenomics measures changes in mRNA levels in cells and tissues following exposure to toxic substances. The resulting information on altered gene expression profiles, associated pathways, and the doses at which these changes occur, are used to identify the underlying mechanisms of toxicity and to predict disease outcomes. We evaluated the applicability of toxicogenomics data in identifying potential lung-specific (genomic datasets are currently available from experiments where mice have been exposed to various ENMs through this common route of exposure) disease outcomes following exposure to ENMs. METHODS:Seven toxicogenomics studies describing mouse pulmonary responses over time following intra-tracheal exposure to increasing doses of carbon nanotubes (CNTs), carbon black, and titanium dioxide (TiO2) nanoparticles of varying properties were examined to understand underlying mechanisms of toxicity. mRNA profiles from these studies were compared to the publicly available datasets of 15 other mouse models of lung injury/diseases induced by various agents including bleomycin, ovalbumin, TNF?, lipopolysaccharide, bacterial infection, and welding fumes to delineate the implications of ENM-perturbed biological processes to disease pathogenesis in lungs. RESULTS:The meta-analysis revealed two distinct clusters-one driven by TiO2 and the other by CNTs. Unsupervised clustering of the genes showing significant expression changes revealed that CNT response clustered with bleomycin injury and bacterial infection models, both of which are known to induce lung fibrosis, in a post-exposure-time dependent manner, irrespective of the CNT's physical-chemical properties. TiO2 samples clustered separately from CNTs and disease models. CONCLUSIONS:These results indicate that in the absence of apical toxicity data, a tiered strategy beginning with short term, in vivo tissue transcriptomics profiling can effectively and efficiently screen new ENMs that have a higher probability of inducing pulmonary pathogenesis.
| S-EPMC4865099 | biostudies-literature
Project description:The mononuclear phagocyte system in the liver is a frequent target for nanoparticles (NPs). A toxicological profiling of metal-based NPs is performed in Kupffer cell (KC) and hepatocyte cell lines. Sixteen NPs are provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences to study the toxicological effects in KUP5 (KC) and Hepa 1-6 cells. Five NPs (Ag, CuO, ZnO, SiO2 , and V2 O5 ) exhibit cytotoxicity in both cell types, while SiO2 and V2 O5 induce IL-1β production in KC. Ag, CuO, and ZnO induced caspase 3 generated apoptosis in both cell types is accompanied by ion shedding and generation of mitochondrial reactive oxygen species (ROS) in both cell types. However, the cell death response to SiO2 in KC differs by inducing pyroptosis as a result of potassium efflux, caspase 1 activation, NLRP3 inflammasome assembly, IL-1β release, and cleavage of gasdermin-D. This releases pore-performing peptide fragments responsible for pyroptotic cell swelling. Interestingly, although V2 O5 induces IL-1β release and delays caspase 1 activation by vanadium ion interference in membrane Na+ /K+ adenosine triphosphate (ATP)ase activity, the major cell death mechanism in KC (and Hepa 1-6) is caspase 3 mediated apoptosis. These findings improve the understanding of the mechanisms of metal-based engineered nanomaterial (ENM) toxicity in liver cells toward comprehensive safety evaluation.
| S-EPMC7263057 | biostudies-literature
Project description:BackgroundDifferences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity.ObjectivesGrantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability.MethodsConsortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells.ResultsThe overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μg/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β.ConclusionsThe results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity.
| S-EPMC3672931 | biostudies-literature
Project description:Proteomic data from engineered nanomaterial- treated THP-1 cells. Time points at 12 hours; 4 biological replicates for each treatment. Human THP-1 cells were either mock-treated (control) or treated with engineered nanomaterials (ENMs). Four biological replicates were used for each sample group (Control, or ENM treatment at either the low or high dosage). In the block design scheme for LC-MS analysis, samples treated with two different ENMs were assign into an analytical block (2 ENM X 2 dosages/ENM X 4 replicates = 16 samples). Four control samples were also included in each block, yielding 20 samples per block. Blocks of samples were divided into two processing batches. Samples in each batch were processed simultaneously from cell culture, to treatment with ENMs, and finally to proteomic sample preparation for LC-MS analysis (including trypsin digestion).
2020-02-05 | MSV000084903 | MassIVE