title: Modulation of apoptotic pathways of macrophages by surface-functionalized multi-walled carbon nanotubes.
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.
authors.affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, China.
authors.forename: Yuanqin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhang
authors.forename: Yange
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Shefang
authors.initials: S
authors.lastname: Ye
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D008264:Macrophages / Q000187:drug effects* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000009:adverse effects* / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D037742:Nanotubes, Carbon