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Modulation of apoptotic pathways of macrophages by surface-functionalized multi-walled carbon nanotubes.

Jiang Y, Zhang H, Wang Y, Chen M, Ye S, Hou Z, Ren L - PLoS ONE (2013)

Bottom Line: However, the potential adverse effects of surface-functionalized CNTs have not been well characterized.The less cytotoxic and apoptotic effect of MWCNTs-PEG compared with MWCNTs-COOH resulted from the lower cellular uptake of MWCNTs-PEG, which resulted in less activation of oxidative stress-responsive pathways, such as p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB.These results demonstrate that surface functionalization of CNTs may alter ROS-mediated cytotoxic and apoptotic response by modulating apoptotic signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, China.

ABSTRACT
Biomedical applications of carbon nanotubes (CNTs) often involve improving their hydrophilicity and dispersion in biological media by modifying them through noncovalent or covalent functionalization. However, the potential adverse effects of surface-functionalized CNTs have not been well characterized. In this study, we functionalized multi-walled CNTs (MWCNTs) via carboxylation, to produce MWCNTs-COOH, and via poly (ethylene glycol) linking, to produce MWCNTs-PEG. We used these functionalized MWCNTs to study the effect of surface functionalization on MWCNTs-induced toxicity to macrophages, and elucidate the underlying mechanisms of action. Our results revealed that MWCNTs-PEG were less cytotoxic and were associated with less apoptotic cell death of macrophages than MWCNTs-COOH. Additionally, MWCNTs-PEG induced less generation of reactive oxygen species (ROS) involving less activation of NADPH oxidase compared with MWCNTs-COOH, as evidenced by membrane translocation of p47(phox) and p67(phox) in macrophages. The less cytotoxic and apoptotic effect of MWCNTs-PEG compared with MWCNTs-COOH resulted from the lower cellular uptake of MWCNTs-PEG, which resulted in less activation of oxidative stress-responsive pathways, such as p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB. These results demonstrate that surface functionalization of CNTs may alter ROS-mediated cytotoxic and apoptotic response by modulating apoptotic signaling pathways. Our study thus provides new insights into the molecular basis for the surface properties affecting CNTs toxicity.

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Related in: MedlinePlus

Cytotoxic effects of MWCNTs-COOH and MWCNTs-PEG on macrophages.(A) RAW 264.7 cells and (B) primary rat peritoneal macrophages were incubated with or without indicated concentrations of f-MWCNTs samples for 24 h. At the end of the incubation period, the WST-1 assay was performed to evaluate the cytotoxicity. Data are representative of three independent experiments and are expressed as the mean ± SD of at least three experiments. *p<0.05 compared to control sample, #p<0.05 compared to MWCNTs-PEG.
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pone-0065756-g002: Cytotoxic effects of MWCNTs-COOH and MWCNTs-PEG on macrophages.(A) RAW 264.7 cells and (B) primary rat peritoneal macrophages were incubated with or without indicated concentrations of f-MWCNTs samples for 24 h. At the end of the incubation period, the WST-1 assay was performed to evaluate the cytotoxicity. Data are representative of three independent experiments and are expressed as the mean ± SD of at least three experiments. *p<0.05 compared to control sample, #p<0.05 compared to MWCNTs-PEG.

Mentions: In a primary screening test, we examined whether MWCNTs-COOH or MWCNTs-PEG were cytotoxic. RAW 264.7 cells were treated with various concentrations of MWCNTs-COOH and MWCNTs-PEG for 24 h, and cell viability was determined by the WST-1 assay. As shown in Figure 2A and B, both MWCNTs-COOH and MWCNTs-PEG at the concentration of 75 µg/mL significantly reduced the viability of RAW 264.7 cells after 24 h of incubation. MWCNTs-PEG was found to be less toxic than MWCNTs-COOH at the same concentration. Similarly, using primary rat peritoneal macrophages, MWCNTs-PEG was also found to be less toxic effect than MWCNTs-COOH. Carbon black is usually used as a negative control and exerted a very minimal effect against RAW 264.7 cells and peritoneal macrophages (Figure 2A, B).


Modulation of apoptotic pathways of macrophages by surface-functionalized multi-walled carbon nanotubes.

Jiang Y, Zhang H, Wang Y, Chen M, Ye S, Hou Z, Ren L - PLoS ONE (2013)

Cytotoxic effects of MWCNTs-COOH and MWCNTs-PEG on macrophages.(A) RAW 264.7 cells and (B) primary rat peritoneal macrophages were incubated with or without indicated concentrations of f-MWCNTs samples for 24 h. At the end of the incubation period, the WST-1 assay was performed to evaluate the cytotoxicity. Data are representative of three independent experiments and are expressed as the mean ± SD of at least three experiments. *p<0.05 compared to control sample, #p<0.05 compared to MWCNTs-PEG.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675050&req=5

pone-0065756-g002: Cytotoxic effects of MWCNTs-COOH and MWCNTs-PEG on macrophages.(A) RAW 264.7 cells and (B) primary rat peritoneal macrophages were incubated with or without indicated concentrations of f-MWCNTs samples for 24 h. At the end of the incubation period, the WST-1 assay was performed to evaluate the cytotoxicity. Data are representative of three independent experiments and are expressed as the mean ± SD of at least three experiments. *p<0.05 compared to control sample, #p<0.05 compared to MWCNTs-PEG.
Mentions: In a primary screening test, we examined whether MWCNTs-COOH or MWCNTs-PEG were cytotoxic. RAW 264.7 cells were treated with various concentrations of MWCNTs-COOH and MWCNTs-PEG for 24 h, and cell viability was determined by the WST-1 assay. As shown in Figure 2A and B, both MWCNTs-COOH and MWCNTs-PEG at the concentration of 75 µg/mL significantly reduced the viability of RAW 264.7 cells after 24 h of incubation. MWCNTs-PEG was found to be less toxic than MWCNTs-COOH at the same concentration. Similarly, using primary rat peritoneal macrophages, MWCNTs-PEG was also found to be less toxic effect than MWCNTs-COOH. Carbon black is usually used as a negative control and exerted a very minimal effect against RAW 264.7 cells and peritoneal macrophages (Figure 2A, B).

Bottom Line: However, the potential adverse effects of surface-functionalized CNTs have not been well characterized.The less cytotoxic and apoptotic effect of MWCNTs-PEG compared with MWCNTs-COOH resulted from the lower cellular uptake of MWCNTs-PEG, which resulted in less activation of oxidative stress-responsive pathways, such as p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB.These results demonstrate that surface functionalization of CNTs may alter ROS-mediated cytotoxic and apoptotic response by modulating apoptotic signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, China.

ABSTRACT
Biomedical applications of carbon nanotubes (CNTs) often involve improving their hydrophilicity and dispersion in biological media by modifying them through noncovalent or covalent functionalization. However, the potential adverse effects of surface-functionalized CNTs have not been well characterized. In this study, we functionalized multi-walled CNTs (MWCNTs) via carboxylation, to produce MWCNTs-COOH, and via poly (ethylene glycol) linking, to produce MWCNTs-PEG. We used these functionalized MWCNTs to study the effect of surface functionalization on MWCNTs-induced toxicity to macrophages, and elucidate the underlying mechanisms of action. Our results revealed that MWCNTs-PEG were less cytotoxic and were associated with less apoptotic cell death of macrophages than MWCNTs-COOH. Additionally, MWCNTs-PEG induced less generation of reactive oxygen species (ROS) involving less activation of NADPH oxidase compared with MWCNTs-COOH, as evidenced by membrane translocation of p47(phox) and p67(phox) in macrophages. The less cytotoxic and apoptotic effect of MWCNTs-PEG compared with MWCNTs-COOH resulted from the lower cellular uptake of MWCNTs-PEG, which resulted in less activation of oxidative stress-responsive pathways, such as p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB. These results demonstrate that surface functionalization of CNTs may alter ROS-mediated cytotoxic and apoptotic response by modulating apoptotic signaling pathways. Our study thus provides new insights into the molecular basis for the surface properties affecting CNTs toxicity.

Show MeSH
Related in: MedlinePlus