Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus?

Our plain-English summary of Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus?, by A.A. Shvedova, E.R. Kisin, D. Porter, et al (Pharmacology & Therapeutics, 2009).

The study

• Authors: A.A. Shvedova, E.R. Kisin, D. Porter, P. Schulte, V.E. Kagan, B. Fadeel, V. Castranova
• Journal: Pharmacology & Therapeutics
• Published: 2009;121(2):192-204
• Type of article: Review
• Cited by: 193 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Nanotechnology is an emerging science involving manipulation of materials at the nanometer scale. There are several exciting prospects for the application of engineered nanomaterials in medicine. However, concerns over adverse and unanticipated effects on human health have also been raised. In fact, the same properties that make engineered nanomaterials attractive from a technological and biomedical perspective could also make these novel materials harmful to human health and the environment. Carbon nanotubes are cylinders of one or several coaxial graphite layer(s) with a diameter in the order of nanometers, and serve as an instructive example of the Janus-like properties of nanomaterials. Numerous in vitro and in vivo studies have shown that carbon nanotubes and/or associated contaminants or catalytic materials that arise during the production process may induce oxidative stress and prominent pulmonary inflammation. Recent studies also suggest some similarities between the pathogenic properties of multi-walled carbon nanotubes and those of asbestos fibers. On the other hand, carbon nanotubes can be readily functionalized and several studies on the use of carbon nanotubes as versatile excipients for drug delivery and imaging of disease processes have been reported, suggesting that carbon nanotubes may have a place in the armamentarium for treatment and monitoring of cancer, infection, and other disease conditions. Nanomedicine is an emerging field that holds great promise; however, close attention to safety issues is required to ensure that the opportunities that carbon nanotubes and other engineered nanoparticles offer can be translated into feasible and safe constructs for the treatment of human disease.

In plain English

This article reviewed published laboratory and animal research on single-walled and multi-walled carbon nanotubes and their possible medical uses. It did not report a new study of people. The authors judged that well-dispersed, purified nanotubes showed relatively low toxicity to cultured cells. One reviewed mouse study found that inhaling non-purified single-walled nanotubes (5 mg/m3, 5 hours a day for 4 days) caused more inflammation, fibrosis and K-ras gene mutations than aspiration of the same nanotubes. Two studies injected multi-walled nanotubes into mouse abdomens. One reported mesothelioma after 6 months in nanotube-exposed and asbestos-exposed mice. The nanotube-exposed mice were heterozygous for the p53 tumor-suppressor gene, a type reported to be especially sensitive to asbestos-induced mesothelioma, and the study was criticized for its very high dose. The other found that long, but not short, nanotubes caused abdominal inflammation similar in magnitude to asbestos. The authors noted that animal studies of multi-walled nanotubes were very limited and inconsistent, and no evidence yet showed nanotubes reach the pleural space. They concluded that a balanced evaluation of risks and benefits is needed before medical use.

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: narrative review of published in vitro, animal and medical-application studies of carbon nanotubes
• Who was studied: published cell-culture and animal (mainly mouse and rat) studies of carbon nanotubes; no human study population
• Exposure: single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT), given by inhalation, aspiration, intratracheal instillation, abdominal injection or in cell culture, with some comparisons to asbestos
• Main results:
  • The authors judged that the cell-culture data favor the conclusion that well-dispersed, purified carbon nanotubes have relatively low cytotoxicity in vitro.
  • In a reviewed mouse study (Shvedova et al., 2008b), inhaling non-purified SWCNT (17.7% iron by weight) at 5 mg/m3, 5 h/day for 4 days was more effective than pharyngeal aspiration (5 to 20 µg/mouse) in causing inflammation, oxidative stress, collagen deposition and fibrosis, and K-ras mutations in C57BL/6 mice.
  • The inhalation exposure gave a calculated lung burden of 5 μg/mouse. The authors stated that workers would reach this burden in less than 1 year at the peak airborne concentrations measured in one occupational setting (data of Maynard et al., 2004).
  • A reviewed study (Takagi et al., 2008) reported mesothelioma 6 months after intraperitoneal injection in MWCNT-exposed and asbestos-exposed mice, but not in fullerene-exposed mice. The MWCNT were given to mice heterozygous for the p53 tumor suppressor, which have been reported to be especially sensitive to asbestos-induced mesothelioma. The study was criticized for its very high dose of 3 mg/mouse.
  • In another reviewed study (Poland et al., 2008), 50 μg/mouse of long, but not short, MWCNT injected into the abdomen caused inflammation of the abdominal wall at seven days. These responses were similar in magnitude to those caused by asbestos.
  • For medical uses, the authors noted that the surface chemistry of carbon nanotubes appears critical to how they behave and distribute in the body.
• The authors' conclusion: The authors concluded that the physico-chemical features driving nanotube toxicity need to be identified. They also concluded that a detailed understanding of nanotube pharmacology and toxicology, and a critical, balanced evaluation of risks and benefits, is required as medical applications are considered.
• Limitations the authors state:
  • Animal studies of MWCNT are very limited and their results are not consistent.
  • No evidence was available that carbon nanotubes can reach the pleural space, so the relevance of the mesothelial cell findings to humans is unknown.
  • Aspiration and intratracheal studies used relatively high bolus doses that may not reflect the chronic lower doses seen in occupational settings.

Topics

Medical terms in this study, explained in our Lexicon: Oxidative Stress, Inflammation.

Related studies

• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)
• Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences — K. Donaldson, C.A. Poland, et al. (2013)
• Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos — A.R. Murray, E.R. Kisin, et al. (2012)
• A critical review of the biological mechanisms underlying the in vivo and in vitro toxicity of carbon nanotubes: The contribution of physico-chemical characteristics — H.J. Johnston, G.R. Hutchison, et al. (2010)
• Multi-walled carbon nanotubes injure the plasma membrane of macrophages — S. Hirano, S. Kanno, et al. (2008)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)

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