Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism

Our plain-English summary of Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: shedding light on fiber entry mechanism, by H. Nagai, S. Toyokuni (Cancer Science, 2012).

The study

• Authors: H. Nagai, S. Toyokuni
• Journal: Cancer Science
• Published: 2012;103(8):1378-90
• Type of article: Review
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The emergence of nanotechnology represents an important milestone, as it opens the way to a broad spectrum of applications for nanomaterials in the fields of engineering, industry and medicine. One example of nanomaterials that have the potential for widespread use is carbon nanotubes, which have a tubular structure made of graphene sheets. However, there have been concerns that they may pose a potential health risk due to their similarities to asbestos, namely their high biopersistence and needle-like structure. We recently found that despite these similarities, carbon nanotubes and asbestos differ in certain aspects, such as their mechanism of entry into mesothelial cells. In the study, we showed that non-functionalized, multi-walled carbon nanotubes enter mesothelial cells by directly piercing through the cell membrane in a diameter- and rigidity-dependent manner, whereas asbestos mainly enters these cells through the process of endocytosis, which is independent of fiber diameter. In this review, we discuss the key differences, as well as similarities, between asbestos fibers and carbon nanotubes. We also summarize previous reports regarding the mechanism of carbon nanotube entry into non-phagocytic cells. As the entry of fibers into mesothelial cells is a crucial step in mesothelial carcinogenesis, we believe that a comprehensive study on the differences by which carbon nanotubes and asbestos fibers enter into non-phagocytic cells will provide important clues for the safer manufacture of carbon nanotubes through strict regulation on fiber characteristics, such as diameter, surface properties, length and rigidity.

© 2012 Japanese Cancer Association.

In plain English

This article was a review, not a new study. The authors summarized published laboratory research comparing carbon nanotubes with asbestos fibers in the development of mesothelial cancer, focusing on how each kind of fiber enters mesothelial and epithelial cells. They also tabulated earlier reports on how single-walled and multi-walled carbon nanotubes enter cells that are not phagocytes. They described their own earlier study, in which multi-walled carbon nanotubes coated with albumin were not endocytosed by two human mesothelial cell lines. Instead, the nanotubes entered the cells by piercing directly through the cell and nuclear membranes, depending on their diameter and rigidity. Asbestos fibers, in contrast, were actively endocytosed by the cells regardless of their diameter. The review reported that asbestos and carbon nanotubes appear to activate macrophages through similar mechanisms, noting that the nanotubes in those experiments were non-functionalized. It also reported that homozygous deletion of the Cdkn2a/2b genes is frequently observed in mesothelioma induced by either. The authors concluded that a positive surface charge and a thin diameter appear to help carbon nanotubes pierce membranes. They said further research is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published laboratory (mainly cell-culture) studies, including a table summarizing reports on carbon nanotube entry into non-phagocytic cells
• Who was studied: No human population; the authors reviewed the published literature on how asbestos fibers and carbon nanotubes enter non-phagocytic cells (mesothelial, epithelial and other cell lines)
• Exposure: Asbestos fibers (chrysotile and crocidolite are named), compared with single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT) of differing length, diameter and surface treatment
• Main results:
  • In the authors' earlier study, albumin-coated multi-walled carbon nanotubes were not endocytosed by two human mesothelial cell lines.
  • In that same earlier study, these nanotubes instead entered by directly piercing the plasma and nuclear membranes, depending on their diameter and rigidity.
  • In the authors' earlier study, asbestos fibers were actively endocytosed by mesothelial cells regardless of fiber diameter.
  • In the authors' previous study, asbestos fibers inside mesothelial cells were surrounded by Rab5a, a marker of early endosomes and phagosomes.
  • Other reviewed studies reported that the serum protein vitronectin, adsorbed onto chrysotile and crocidolite, enhanced asbestos uptake by mesothelial and epithelial cells.
  • The reviewed literature reported that homozygous deletion of the Cdkn2a/2b tumor suppressor genes is frequently observed in both asbestos-induced and carbon nanotube-induced mesothelioma.
  • Reviewed studies reported that uptake of either asbestos or carbon nanotubes by macrophages activates the NLRP3 inflammasome.
  • The authors said asbestos fibers and carbon nanotubes appear to activate macrophages through similar mechanisms, and noted that the carbon nanotubes used in those experiments were non-functionalized.
• The authors' conclusion: The authors concluded that, based on current evidence, a positive surface charge and a thin diameter appear to be two important factors in carbon nanotubes' ability to pierce membranes, and that specific surface ligands allow larger nanotubes to be taken in by endocytosis. They said further research on fiber entry is warranted.
• Limitations the authors state:
  • The authors noted that methods for preparing fiber suspensions and for characterizing fibers differ between laboratories, which could explain differing results.
  • The authors noted that the movement through the body and persistence of uncoated (pristine) carbon nanotubes still need to be investigated.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, biopersistence, Mesothelial Cells.

Related studies

• Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats — H. Nagai, Y. Okazaki, et al. (2013)
• Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences — K. Donaldson, C.A. Poland, et al. (2013)
• Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells — M. Pacurari, X.J. Yin, et al. (2008)
• Chronic exposure to carbon nanotubes induces invasion of human mesothelial cells through matrix metalloproteinase-2 — W. Lohcharoenkal, L. Wang, et al. (2013)
• Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro — S. Sridharan, A. Taylor-Just, et al. (2021)
• Neoplastic-like transformation effect of single-walled and multi-walled carbon nanotubes compared to asbestos on human lung small airway epithelial cells — L. Wang, T.A. Stueckle, et al. (2014)

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