Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane

Eldridge, Brittany N.; Xing, Fei; Fahrenholtz, Cale D.; Singh, Ravi

doi:10.1016/j.tiv.2017.03.002

Cited by 17 publications

(5 citation statements)

References 63 publications

(93 reference statements)

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“…48 Hence, surface functionalization enables a proper way to reduce the cytotoxicity of CNTs through effective cellular uptake processes. 49 In addition, functionalization of CNTs directly affects cellular uptake quality and the cellular internalization mechanisms mentioned above. In Table 4, functionalized CNTs and their effect on solubility, toxicity, effective cellular internalization mechanisms, etc.…”

Section: Functionalizationmentioning

confidence: 99%

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers

Zare

Ahmadi

Ghasemi

et al. 2021

IJN

200

115

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Section: Functionalizationmentioning

confidence: 99%

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers

Zare

Ahmadi

Ghasemi

et al. 2021

IJN

200

115

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“…An additional confounding factor in assessment of the toxic effects of nanomaterials, including AgNPs, is that they can interfere with assays reliant upon optical absorbance, fluorescence, or luminescence measurements [ 48 – 51 ]. Nanoparticles themselves could absorb or scatter light, fluoresce, or increase autofluorescence in cells.…”

Section: Discussionmentioning

confidence: 99%

“…The potential for nanoparticles to affect background absorbance or fluorescence measurements in part can be accounted for by subtracting background measurements taken from label-free, nanoparticle treated cells as we have done in the studies reported here. Nanoparticles also may increase or quench fluorescence from certain fluorophores, quench luminescence, or potentially affect the reaction rates for formation of substrates used to assess cell viability [ 48 – 51 ]. Because these types of interference are challenging to assess under experimental conditions used for cell-based assays, cell-free systems commonly are used.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of cell death induced by silver nanoparticles is distinct from silver cations

et al. 2021

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Background Precisely how silver nanoparticles (AgNPs) kill mammalian cells still is not fully understood. It is not clear if AgNP-induced damage differs from silver cation (Ag+), nor is it known how AgNP damage is transmitted from cell membranes, including endosomes, to other organelles. Cells can differ in relative sensitivity to AgNPs or Ag+, which adds another layer of complexity to identifying specific mechanisms of action. Therefore, we determined if there were specific effects of AgNPs that differed from Ag+ in cells with high or low sensitivity to either toxicant. Methods Cells were exposed to intact AgNPs, Ag+, or defined mixtures of AgNPs with Ag+, and viability was assessed. The level of dissolved Ag+ in AgNP suspensions was determined using inductively coupled plasma mass spectrometry. Changes in reactive oxygen species following AgNP or Ag+ exposure were quantified, and treatment with catalase, an enzyme that catalyzes the decomposition of H2O2 to water and oxygen, was used to determine selectively the contribution of H2O2 to AgNP and Ag+ induced cell death. Lipid peroxides, formation of 4-hydroxynonenol protein adducts, protein thiol oxidation, protein aggregation, and activation of the integrated stress response after AgNP or Ag+ exposure were quantified. Lastly, cell membrane integrity and indications of apoptosis or necrosis in AgNP and Ag+ treated cells were examined by flow cytometry. Results We identified AgNPs with negligible Ag+ contamination. We found that SUM159 cells, which are a triple-negative breast cancer cell line, were more sensitive to AgNP exposure less sensitive to Ag+ compared to iMECs, an immortalized, breast epithelial cell line. This indicates that high sensitivity to AgNPs was not predictive of similar sensitivity to Ag+. Exposure to AgNPs increased protein thiol oxidation, misfolded proteins, and activation of the integrated stress response in AgNP sensitive SUM159 cells but not in iMEC cells. In contrast, Ag+ cause similar damage in Ag+ sensitive iMEC cells but not in SUM159 cells. Both Ag+ and AgNP exposure increased H2O2 levels; however, treatment with catalase rescued cells from Ag+ cytotoxicity but not from AgNPs. Instead, our data support a mechanism by which damage from AgNP exposure propagates through cells by generation of lipid peroxides, subsequent lipid peroxide mediated oxidation of proteins, and via generation of 4-hydroxynonenal (4-HNE) protein adducts. Conclusions There are distinct differences in the responses of cells to AgNPs and Ag+. Specifically, AgNPs drive cell death through lipid peroxidation leading to proteotoxicity and necrotic cell death, whereas Ag+ increases H2O2, which drives oxidative stress and apoptotic cell death. This work identifies a previously unknown mechanism by which AgNPs kill mammalian cells that is not dependent upon the contribution of Ag+ released in extracellular media. Understanding precisely which factors drive the toxicity of AgNPs is essential for biomedical applications such as cancer therapy, and of importance to identifying consequences of unintended exposures.

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“…They report that oxidized soot was more cytotoxic than untreated, but did not differ in its induction of IL-8 secretion. In contrast, Eldridge et al evaluated toxicity by exposing the microvascular endothelial cells with short and thin MWCNT, with or without oxidation treatment and with or without phospholipid-polyethylene glycol (PL-PEG) coating [58]. They reported that coated MWCNT was cytotoxic, with greater toxicity from untreated MWCNT, whereas uncoated MWCNT was not cytotoxic with or without oxidation treatment.…”

Section: Discussionmentioning

confidence: 99%

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

et al. 2020

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One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs.

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Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane

Cited by 17 publications

References 63 publications

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers

Carbon Nanotubes: Smart Drug/Gene Delivery Carriers

The mechanism of cell death induced by silver nanoparticles is distinct from silver cations

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

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