Asbestos-like pathogenicity of long carbon nanotubes alleviated by chemical functionalization.

Carbon nanotubes (CNTs) are considered one of the most popular types of nanomaterials and in the last few years have gained tremendous interest in a wide range of applications due to their unique physical, chemical, and electronic properties. Multi-walled carbon nanotubes (MWNTs) consist of sheets of carbon atoms rolled up into multiple concentric hollow tubular structures. The lack of dispersibility of pristineMWNTs in most solvents is owing to strong inter-tube van der Waals forces and this has been an obstacle for their effective use in biological applications and material sciences (i.e. composites). This may be largely overcome by surface modification of the nanotube backbone, allowing application of CNTs in biomedical applications. Some types of chemically functionalized CNTs have shown great advantages for use as delivery systems because of their capacity to pierce cellular membranes and translocate directly into the cytoplasm, providing a method for effective drug and macromolecule intracellular transport. Moreover, chemical surface-functionalization strategies can improve the colloidal properties of the CNT dispersions and result in populations of individualized MWNTs in physiological environments that have the capacity for glomerular translocation, leading to rapid urinary excretion. Such biokinetic processes are also extremely important to determine the biopersistence and ultimately the potential risk from medical use of carbon nanotubes. The use of CNTs—particularly in mass-scale, industrial applications—is currently considered with apprehension owing to their yet undefined safety profile and their potential environmental and health risks, especially given their structural resemblance to asbestos fibers. Several research groups have attempted to determine the carcinogenic risks that may be associated with intended or unintentional exposure to CNTs using various in vivo models. The first study that highlighted the importance of carbon nanotube length characteristics was carried out by Poland et al. using pristine (non-functionalized), long CNTs in a structure– toxicity study, which was originally validated with asbestos fibers. According to this method, which relates length and biopersistence of asbestos fibers to the development of mesothelioma (cancer of the pleural membrane), non-functionalized MWNTs longer than 20 mm were found to trigger an inflammatory response and result in granuloma formation seven days after intra-peritoneal exposure, similar to long asbestos fibers (LFA, long fiber amosite). This was thought to be due to induction of a process termed “frustrated phagocytosis” as resident and recruited macrophages attempt unsuccessfully to remove the long fibers from the mesothelium. Similar conclusions regarding the risk of unwanted