Sirs
We read with great interest and appreciated very much the article by Ferrari1 on the fascinating opportunities and challenges of nanotechnology in providing breakthroughs in the therapy against cancer. We, obviously, agree that nanomaterials provide realistic benefits in diagnosis, imaging and drug delivery. However, as 'nanotoxicologists', we would like to comment on the possible adverse health effects of these new materials.
Ferrari fears that regulatory approval will have to be issued for each agent, and then for their combination. It is important to point out that the potential toxicity of nanoparticles might not be detected by conventional toxicity tests. Thus, we have recently shown that intravenous or intratracheal instillation of amine-modified polystyrene nanoparticles (60 nm) to hamsters enhance peripheral vascular thrombosis when an endothelial lesion has been produced2,3. This thrombosis model offers the advantage that it studies 'compromised' individuals (that is, it mimics people with pre-existing diseases such as thrombosis-prone cancer patients) and, therefore, it reflects a realistic experimental set-up for the human situation. Moreover, in contrast to amine-modified polystyrene nanoparticles, we found no increase of thrombosis with unmodified or carboxylate-modified nanoparticles of similar diameter (60 nm). This demonstrates the need of performing testing for each type of nanoparticle.
It has also been shown that pulmonary exposure to nanoparticles might cause lung inflammation3,4. Recent studies have reported that inhaled nanoparticles are not only able translocate into the blood5,6,7 and affect the cardiovascular system, but they can also reach the olfactory bulbs and then migrate throughout the brain8.
In conclusion, we believe that these observations illustrate the need to perform appropriate evaluation of the health risk of nanoparticles to different organs (for example, heart, brain, lung and blood) and in different conditions (health and diseases). Consequently, the necessary time must be taken to ensure that careful and appropriate toxicity testings have been performed for ascertaining the suitability of each agent for clinical use.
Finally, the phenomenal promise of nanotechnology for medical purposes (where the benefits for the patients might justifiably outweigh the risk of side effects) should not obscure the potential health risks of occupational or environmental exposure to engineered nanomaterials produced for other purposes9.
References
Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nature Rev. Cancer 5, 161–171 (2005).
Nemmar, A. et al. Ultrafine particles affect experimental thrombosis in an in vivo hamster model. Am. J. Respir. Crit. Care Med. 166, 998–1004 (2002).
Nemmar, A., Hoylaerts, M., Hoet, P. H., Vermylen, J. & Nemery, B. Size effect of intratracheally instilled ultrafine particles on pulmonary inflammation and vascular thrombosis. Toxicol. Appl. Pharmacol. 186, 38–45 (2003).
Oberdörster, G. Pulmonary effects of inhaled ultrafine particles. Int. Arch. Occup. Environ. Health 74, 1–8 (2001).
Nemmar, A. et al. Passage of inhaled particles into the blood circulation in humans. Circulation 105, 411–414 (2002).
Nemmar, A. et al. Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am. J. Respir. Crit. Care Med. 164, 1665–1668 (2001).
Oberdörster, G. et al. Extrapulmonary translocation of ultrafine carbon particle following whole-body inhalation exposure of rats. J. Toxicol. Environ. Health A 65, 1531–1543 (2002).
Oberdörster, G. et al. Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 16, 437–445 (2004).
Hoet, P. H., Bruske-Hohlfeld, I. & Salata, O. V. Nanoparticles — known and unknown health risks. J. Nanobiotechnology 2, 12 (2004).
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Nemmar, A., Hoet, P., Nemery, B. et al. Comment. Nat Rev Cancer 5, 580 (2005). https://doi.org/10.1038/nrc1566-c1
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DOI: https://doi.org/10.1038/nrc1566-c1
