Bionanotechnology: From Self-Assembly to Cell Biology
Health effects of nanomaterials T.D. Tetley1 National Heart and Lung Institute, Imperial College London, London SW3 6LY, U.K.
Abstract With the rapid growth of nanotechnology and future bulk manufacture of nanomaterials comes the need to determine, understand and counteract any adverse health effects of these materials that may occur during manufacture, during use, or accidentally. Nanotechnology is expanding rapidly and will affect many aspects of everyday life; there are already hundreds of products that utilize nanoparticles. Paradoxically, the unique properties that are being exploited (e.g. high surface reactivity and ability to cross cell membranes) might have negative health impacts. The rapid progress in development and use of nanomaterials is not yet matched by toxicological investigations. Epidemiological studies implicate the ultrafine (nanosized) fraction of particulate air pollution in the exacerbation of cardiorespiratory disease and increased morbidity. Experimental animal studies suggest that the increased concentration of nanoparticles and higher reactive surface area per unit mass, alongside unique chemistry and functionality, is important in the acute inflammatory and chronic response. Some animal models have shown that nanoparticles which are deposited in one organ (e.g. lung and gut) may access the vasculature and target other organs (e.g. brain and liver). The exact relationship between the physicochemistry of a nanoparticle, its cellular reactivity, and its biological and systemic consequences cannot be predicted. It is important to understand such relationships to enjoy the benefits of nanotechnology without being exposed to the hazards.
The advent of nanotechnology opens up a wealth of opportunities across a broad spectrum of applications, including medicine, cosmetics, electronics, textiles and engineering. The number of consumer products that utilize nanotechnology is already in the hundreds and is, predictably, increasing (http://www.nanotechproject.org/consumerproducts). This reflects the unique and diverse properties of nanomaterials which, at the nanoscale, are quite different to those of the same compound on a larger scale. Thus nano-sized materials are being harnessed to improve existing products and to create new products. The rate of growth is exponential. However, with the exciting prospect that the nanosciences, nanotechnology and production of nanomaterials will improve many aspects of everyday life, the rapid advance in this area has not been matched by investigations into possible hazards and risks of working and living with these new materials. In the rush to exploit the potential of nanotechnology, the issues surrounding its safety are being left behind. This is despite the recommendations of The Royal Society and Royal Academy of Engineering in 2004 (Nanoscience and nanotechnologies: opportunities and uncertainties; http://www.nanotec.org.uk), and a number of other significant groups since then, including DEFRA (Department for Environment, Food and Rural Affairs) (Characterising the potential risks posed by engineered nanoparticles; a first U.K. Government research report; http://www.defra.gov.uk/environment/nanotech/ Key words: cardiovascular system, inflammation, lung, nanoparticle, nanotube, respiratory disease. Abbreviations used: CNT, carbon nanotube; PM, particulate matter. 1 email
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research/pdf/nanoparticles-riskreport.pdf) and the scientific community [1–3]. It is feared that there may be repercussions in the future, particularly with respect to effects on the environment and human health and safety, if these issues are insufficiently addressed.
Historical lessons Should we be concerned? Taking a historical perspective, the devastating effects of inhaled asbestos on the respiratory system, fibrosis and lung cancer, including mesothelioma (a rare, untreatable form of cancer), are now well known. However, even though the fibrotic effects of inhaled asbestos were described early in the 20th Century [4], and carcinogenic effects were first described in 1935 [5], while pleural mesothelioma was related to exposure to low levels of crocidolite in the early 1960s [6], the exceptional qualities and versatility of the material meant that it was widely, and increasingly, used for many more years before regulatory control was introduced in the U.K. in the 1980s and, ultimately, importation to the U.K. was prohibited in 1992 [Asbestos Licensing Regulations (1983); Control of Asbestos at Work Regulations (1987); Asbestos Prohibition Regulation (1992)]. Of significance to the future understanding of any unwanted health effects of nanoparticles is that the development and nature of the pulmonary effects of asbestos critically depend on its physicochemistry and exposure dose. It has been suggested that nanoparticles could become ‘the asbestos of the 21st Century’ [3]. The diversity and range of nanoparticle applications suggest that any environmental or health effects could be wide-ranging. C 2007
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Figure 1 Flow diagram highlighting the hypothetical effects of inhaled nanoparticles on the lungs and cardiovasculature
Lessons from air pollution studies The health effects of the particulate component of ambient air pollution have recently come under the spotlight. Elevated ambient particulate air pollution correlates with increased hospitalization, associated with increased morbidity and mortality, for respiratory and cardiovascular diseases [7– 11]. The presence of an existing respiratory disease, such as asthma, chronic obstructive pulmonary disease and lung cancer [8,12,13], renders individuals susceptible. An increase of only 10 µg/m3 of ambient PM (particulate matter) less than 10 microns (PM10 ) or less than 2.5 microns (PM2.5 ) in aerodynamic diameter has been associated with increased risk, and incidence of, myocardial infarct, independently of other risk factors [9,14,15]. Other cardiovascular effects include raised blood pressure [16] and reduced heart rate variability [17]. Furthermore, increased PM2.5 is associated with the development of atherosclerosis in individuals previously regarded as healthy [18]. While the respiratory effects of increased ambient particulate air pollution might have been anticipated, the striking cardiovascular effects are puzzling and there is currently no clear explanation. Significantly, the ultrafine, nano-sized component of particulate air pollution has been implicated.
The lungs as a target for nano-sized substances (Figure 1) Large particles of inhaled organic and inorganic matter are normally cleared after depositing in the conducting airways, where they are trapped in the mucus or phagocytosed by C 2007
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macrophages and transported to the throat, via the mucociliary escalator, and swallowed or expectorated. Smaller particles will be deposited in the small airways and respiratory units of the lungs where they are phagocytosed by macrophages, or, if too small, the particles escape phagocytosis and interact with the epithelium. For a given particulate mass, the number of nanoparticles (particles with a diameter of 100, being
