Physical interactions of nanoparticles with biological membranes: The observation of nanoscale hole formation

Many classes of nanoparticles have been synthesized and characterized over the last several decades. Interesting examples include gold,¹ metal and metal oxide,^2,3 semiconductor,⁴ and organic nanoparticles.⁵ Considerable effort has also been expended in the area of surface functionalization.⁶ These materials show great promise for many kinds of applications including catalysis,⁷ medical diagnosis and therapy,^8,9 sensors,^10-14 cosmetics,¹⁵ and coatings.¹⁶ The opportunity for revolutionary improvement in important technologies has led to considerable excitement and spawned the National Nanotechnology Initiative (www.nano.gov). Further, substantial international efforts are underway with at least 30 countries having initiated national activities in this field.¹⁷. As has frequently been the case with new technologies, our ability to create has outstripped our understanding of the impact of the creation. This is a particular concern with synthetic nanoparticles because they are similar in size to the major classes of biologically active materials used to effect chemical change (proteins), store information (DNA and RNA), and provide structure and transport (membranes, actin, microtubules). Thus, the toxicology of synthetic nanoparticles has become a pressing question. In particular, is the toxicological database developed for ultrafine particles (20-100 nm) sufficient to explain and predict the behavior anticipated for these newly synthesized particles? Or, viewed from another perspective, what can we learn about the mechanism of toxicity of ultrafine particles by employing well-characterized nanoparticles. A flurry of reviews has appeared in the literature over the last year^18-20 and a new field of "nanotoxicology" appears to be forming, complete with a new journal launched in January of 2005 of the same name. A variety of studies are underway in the United States of America such as those led by the Environmental Protection Agency,²⁰ the National Toxicology Program of the National Institute for Environmental Health and Safety (NIEHS) (ntp-server.niehs.nih.gov) and the Nanotechnology and Health and Safety Research Program led by the National Institute for Occupational Safety and Health (NIOSH) (www.cdc.gov/niosh/topics/nanotech/). In addition to the US-based efforts, significant reports have arisen from the English Royal Society (www.nanotec.org.uk/finalReport.htm). Lastly, an international industrial/governmental/academic consortium has been formed, the International Council on Nanotechnology or ICON (icon.rice.edu) to provide information and address issues of nanomaterials standards.