Surface Charge and Cellular Processing of Covalently Functionalized Multiwall Carbon Nanotubes Determine Pulmonary Toxicity

详细信息    查看全文

• 作者：Ruibin Li ; Xiang Wang ; Zhaoxia Ji ; Bingbing Sun ; Haiyuan Zhang ; Chong Hyun Chang ; Sijie Lin ; Huan Meng ; Yu-Pei Liao ; Meiying Wang ; Zongxi Li ; Angela A. Hwang ; Tze-Bin Song ; Run Xu ; Yang Yang ; Jeffrey I. Zink ; Andr茅 E. Nel ; Tian Xia
• 刊名：ACS Nano
• 出版年：2013
• 出版时间：March 26, 2013
• 年：2013
• 卷：7
• 期：3
• 页码：2352-2368
• 全文大小：1167K
• 年卷期：v.7,no.3(March 26, 2013)
• ISSN：1936-086X

文摘

Functionalized carbon nanotubes (f-CNTs) are being produced in increased volume because of the ease of dispersion and maintenance of the pristine material physicochemical properties when used in composite materials as well as for other commercial applications. However, the potential adverse effects of f-CNTs have not been quantitatively or systematically explored. In this study, we used a library of covalently functionalized multiwall carbon nanotubes (f-MWCNTs), established from the same starting material, to assess the impact of surface charge in a predictive toxicological model that relates the tubes鈥?pro-inflammatory and pro-fibrogenic effects at cellular level to the development of pulmonary fibrosis. Carboxylate (COOH), polyethylene glycol (PEG), amine (NH₂), sidewall amine (sw-NH₂), and polyetherimide (PEI)-modified MWCNTs were successfully established from raw or as-prepared (AP-) MWCNTs and comprehensively characterized by TEM, XPS, FTIR, and DLS to obtain information about morphology, length, degree of functionalization, hydrodynamic size, and surface charge. Cellular screening in BEAS-2B and THP-1 cells showed that, compared to AP-MWCNTs, anionic functionalization (COOH and PEG) decreased the production of pro-fibrogenic cytokines and growth factors (including IL-1尾, TGF-尾1, and PDGF-AA), while neutral and weak cationic functionalization (NH₂ and sw-NH₂) showed intermediary effects. In contrast, the strongly cationic PEI-functionalized tubes induced robust biological effects. These differences could be attributed to differences in cellular uptake and NLRP3 inflammasome activation, which depends on the propensity toward lysosomal damage and cathepsin B release in macrophages. Moreover, the in vitro hazard ranking was validated by the pro-fibrogenic potential of the tubes in vivo. Compared to pristine MWCNTs, strong cationic PEI-MWCNTs induced significant lung fibrosis, while carboxylation significantly decreased the extent of pulmonary fibrosis. These results demonstrate that surface charge plays an important role in the structure鈥揳ctivity relationships that determine the pro-fibrogenic potential of f-CNTs in the lung.

Keywords:

multiwall carbon nanotube; surface functionalization; charge; NLRP3 inflammasome; lung fibrosis