Length, but Not Reactive Edges, of Cup-stack MWCNT Is Responsible for Toxicity and Acute Lung Inflammation

Raymond F. Hamilton, Shuji Tsuruoka, Nianqiang Wu, Michael Wolfarth, Dale W. Porter, Melisa Bunderson-Schelvan, Andrij Holian

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Multiwalled carbon nanotube (MWCNT) toxicity after inhalation has been associated with size, aspect ratio, rigidity, surface modification, and reactive oxygen species production. In this study, we investigated a series of cup-stacked MWCNT prepared as variants of the Creos 24PS. Mechanical chopping produced a short version (AR10) and graphitization to remove active reaction sites by extreme heat (2,800°C; Creos 24HT) to test the contribution of length and alteration of potential reaction sites to toxicity. The 3 MWCNT variants were tested in vitro in a human macrophage–like cell model and with C57BL/6 alveolar macrophages for dose-dependent toxicity and NLRP3 inflammasome activation. The 24PS and 24HT variants showed significant dose-dependent toxicity and inflammasome activation. In contrast, the AR10 variant showed no toxicity or bioactivity at any concentration tested. The in vivo results reflected those observed in vitro, with the 24PS and 24HT variants resulting in acute inflammation, including elevated polymorphonuclear counts, Interleukin (IL)-18, cathepsin B, and lactate dehydrogenase in isolated lung lavage fluid from mice exposed to 40 µg MWCNT. Taken together, these data indicate that length, but not the absence of proposed reaction sites, on the MWCNT influences particle bioactivity.

Original languageEnglish
Pages (from-to)62-74
Number of pages13
JournalToxicologic Pathology
Issue number1
StatePublished - Jan 1 2018


The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Shuji Tsur-uoka was supported by the Center of Innovation Program, “Global Aqua Innovation Center for Improving Living Standards and Water-sustainability” from Japan Science and Technology Agency, JST.

FundersFunder number
Japan Science and Technology Agency


    • MWCNT
    • NLRP3 inflammasome
    • ROS
    • macrophage
    • nanomaterials


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