Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis
Open accessAbstract
Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameter-dependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2–20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health.
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Multi-walled carbon nanotube of ∼50-nm diameter is also a risk for malignant mesothelioma.
“As an example, multi-walled carbon nanotube of ∼50-nm diameter is also a risk for malignant mesothelioma [42,43].”
From Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin (2021) · cites this paper as [42]
For individual thin fibres of low flexural rigidity, macrophages may compactify such fibres during internalization.
“For individual thin fibres of low flexural rigidity, a term shortened to ‘rigidity’ subsequently, it was suggested that macrophages may compactify such fibres during internalization [19].”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [19]
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- Authors
- Nagai, H., Okazaki, Y., Chew, S. H., Misawa, N., Yamashita, Y., Akatsuka, S., Ishihara, T., Yamashita, K., Yoshikawa, Y., Yasui, H., Jiang, L., Ohara, H., Takahashi, T., Ichihara, G., Kostarelos, K., Miyata, Y., Shinohara, H., & Toyokuni, S.
- Affiliations
- Kyoto University (JP)
- Nagoya University (JP)
- Kyoto Pharmaceutical University (JP)
- Departments of dMolecular Carcinogenesis and
- University of London (GB)
- Nagoya University Institute for Advanced Research (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-11-14
- Volume
- 108
- Issue
- 49
- Pages
- E1330-8
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3241783
- OpenAlex
- W2112844455
- Cited by
- 535
- References
- 52
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 21 · 2023: 37 · 2022: 38 · 2021: 43 · 2020: 53 · 2019: 32 · 2018: 28 · 2017: 34 · 2016: 43 · 2015: 55 · 2014: 38 · 2013: 44 · 2012: 38
- FWCI
- 33.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Verband der Chemischen Industrie
- Ministry of Education, Culture, Sports, Science and Technology
- Princess Takamatsu Cancer Research Fund (10-24213)
- Japan Society for the Promotion of Science (23590394, 23659326, 22390120)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Keywords
- multi-walled carbon nanotubes, nanotube diameter, nanotube crystallinity, mesothelial cells, mesothelioma, cytotoxicity, macrophages, inflammation, tumor suppressor, nanoparticle toxicity, carbon nanomaterials
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Epithelial Cells, Epithelium, Humans, Macrophages, Mesothelioma, Microscopy, Electron, Scanning, Mutation, Gene Expression, Cytokines, Gene Deletion, Cyclin-Dependent Kinase Inhibitor p16, Reverse Transcriptase Polymerase Chain Reaction, Nanotubes, Carbon, Microscopy, Electron, Transmission, Cyclin-Dependent Kinase Inhibitor p15, Rats, Comparative Genomic Hybridization
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