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 p47phox and p67phox 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.
Highlights
Motivated by their various novel properties, engineered nanomaterials have been increasingly considered as biomaterials for biomedical and pharmaceutical applications [1]
We found that multi-walled CNTs (MWCNTs)-PEG were less cytotoxic and associated with less apoptotic cell death compared with MWCNTs-COOH, demonstrating the role of surface properties on carbon nanotubes (CNTs) toxicity
transmission electron microscope (TEM) images (Figure 1A, B) demonstrated that both of the fMWCNT samples were largely free from amorphous carbon and catalytic metals
Summary
Motivated by their various novel properties, engineered nanomaterials have been increasingly considered as biomaterials for biomedical and pharmaceutical applications [1]. Previous studies have indicated that pure multi-walled CNTs (MWCNTs) can injure the plasma membrane of human macrophages [9] and rat astrocytes [10]. These observations suggest that pure CNTs without surface modification are cytotoxic to certain mammalian cells. With a wide range of biomedical applications, different types of surface-modified CNTs should be systematically evaluated in terms of cellular uptake and cytotoxicity
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