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

Content Provider	PubMed Central
Author	Li, Ruibin Wang, Xiang Ji, Zhaoxia Sun, Bingbing Zhang, Haiyuan Chang, Chong Hyun Lin, Sijie Meng, Huan Liao, Yu-pei Wang, Meiying Li, Zongxi Hwang, Angela Song, Tze-bin Xu, Run Yang, Yang Zink, Jeffrey I. Nel, André E. Xia, Tian
Abstract	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, and 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’ pro-inflammatory and pro-fibrogenic effects at cellular level to the development of pulmonary fibrosis. Carboxylated (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-1β, TGF-β1 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 towards 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 PEIMWCNTs 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-activity relationships that determine the pro-fibrogenic potential of f-CNTs in the lung.
Related Links	http://dx.doi.org/10.1021/nn305567s
Ending Page	2368
Page Count	17
Starting Page	2352
File Format	PDF
ISSN	19360851
e-ISSN	1936086X
Journal	ACS nano
Issue Number	3
Volume Number	7
Language	English
Publisher Date	2013-03-26
Access Restriction	Open
Subject Keyword	Engineering(all) Physics and Astronomy(all) Materials Science(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Physics and Astronomy Engineering

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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