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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

Representative TEM and SEM images of (A, C) MWCNTs-COOH and (B, D) MWCNTs-PEG.(E) FT-IR spectra of MWCNTs-COOH and MWCNTs-PEG.
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pone-0065756-g001: Representative TEM and SEM images of (A, C) MWCNTs-COOH and (B, D) MWCNTs-PEG.(E) FT-IR spectra of MWCNTs-COOH and MWCNTs-PEG.

Mentions: TEM images (Figure 1A, B) demonstrated that both of the f-MWCNT samples were largely free from amorphous carbon and catalytic metals. SEM images (Figure 1C, D) showed a uniform surface coating of PEG on MWCNTs after functionalization, which resulted in an increase of the average diameter of the MWCNTs-PEG to 27.3±12.5 nm (Table 1). XPS analysis suggested that the surface of the MWCNTs was significantly modified with carboxylic acid groups (-COOH) after acid treatment, as well as successively functionalized with PEG (Table S1). The chemical compositions of MWCNTs-COOH and MWCNTs-PEG were further confirmed by FT-IR spectra (Figure 1E). TGA analysis showed that the amount of carboxylic acid groups and PEG bound to the MWCNTs was about 11.3 wt% and 27.4 wt%, respectively. ICP-MS data showed that the iron impurity of MWCNTs-COOH and MWCNTs-PEG was less than 0.0074% and 0.0042% by weight, respectively (Table 1). The zeta potential of the MWCNTs-COOH and MWCNTs-PEG in RPMI1640 medium was −20.2 mV and −35.6 mV, respectively, indicating that MWCNTs-PEG are possibly more stable in medium compared with the MWCNTs-COOH.


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)

Representative TEM and SEM images of (A, C) MWCNTs-COOH and (B, D) MWCNTs-PEG.(E) FT-IR spectra of MWCNTs-COOH and MWCNTs-PEG.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065756-g001: Representative TEM and SEM images of (A, C) MWCNTs-COOH and (B, D) MWCNTs-PEG.(E) FT-IR spectra of MWCNTs-COOH and MWCNTs-PEG.
Mentions: TEM images (Figure 1A, B) demonstrated that both of the f-MWCNT samples were largely free from amorphous carbon and catalytic metals. SEM images (Figure 1C, D) showed a uniform surface coating of PEG on MWCNTs after functionalization, which resulted in an increase of the average diameter of the MWCNTs-PEG to 27.3±12.5 nm (Table 1). XPS analysis suggested that the surface of the MWCNTs was significantly modified with carboxylic acid groups (-COOH) after acid treatment, as well as successively functionalized with PEG (Table S1). The chemical compositions of MWCNTs-COOH and MWCNTs-PEG were further confirmed by FT-IR spectra (Figure 1E). TGA analysis showed that the amount of carboxylic acid groups and PEG bound to the MWCNTs was about 11.3 wt% and 27.4 wt%, respectively. ICP-MS data showed that the iron impurity of MWCNTs-COOH and MWCNTs-PEG was less than 0.0074% and 0.0042% by weight, respectively (Table 1). The zeta potential of the MWCNTs-COOH and MWCNTs-PEG in RPMI1640 medium was −20.2 mV and −35.6 mV, respectively, indicating that MWCNTs-PEG are possibly more stable in medium compared with the MWCNTs-COOH.

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