February 21, 2006
Making Nanotubes Water-Soluble, Perhaps Safer
While there is some question about the ultimate biocompatibility of carbon nanotubes, investigators have found that chemical modifications that render carbon nanotubes soluble in water also appear to increase the biocompatibility of these promising nanomaterials. Two new reports, one describing a facile method for making water-soluble nanotubes, the other investigating how water-soluble nanotubes behave in mice, provide further impetus to the development of carbon nanotubes for biomedical use.
In the first paper, published in the Journal of the American Chemical Society, a team led by Somenath Mitra, Ph.D., at the New Jersey Institute of Technology, described a quick, simple, and reproducible method to produce water-soluble carbon nanotubes. The resulting carbon nanotubes are 125 times more water-soluble than existing ones. In addition, the new nanotubes, following a short heat treatment, can conduct electricity as well as the non-soluble ones do, which could prove important in microfluidics and biosensing applications.
To achieve these results the researchers added carbon nanotubes to a mixture of nitric acid and sulfuric acid. They then heated the mixture in a microwave oven for a mere three minutes, triggering chemical modifications of the tubes that resulted in their being covered with negatively-charged carboxylate and sulfonate groups, similar to those present in acetic acid or salts of sulfuric acid, respectively. The high negative charge of the resulting tubes increases their water solubility from around 0.08 milligrams of nanotube per milliliter of water to as high as 10 milligrams of nanotube per milliliter of water.
Further analysis of the new nanotubes showed that approximately one in three carbon atoms in the nanotubes contained a carboxylate group, while one in ten had a sulfonate group. Having both carboxylate and sulfonate groups present provides an opportunity to add multiple functionality to the surfaces of these nanotubes. For example, it might be possible to attach a tumor targeting group to sulfonate groups and an antitumor drug to the carboxylate groups.
The second paper, which appears in the Proceedings of the National Academy of Science USA, alleviates some concerns over the safety of using water-soluble carbon nanotubes in biomedical applications. An international team led by Kostas Kostarelos Ph.D., at the University of London, began its study using carbon nanotubes with one of two different modifications designed to render the nanotubes soluble in water; this team used different methods to prepare the tubes for this study compared to the one developed by the New Jersey Institute of Technology group.
One of the modifications enabled the researchers to complex the nanotubes with the radioactive element indium-111, which is widely used to study biodistribution of potential therapeutic agents. After adding this radioisotope to the nanotubes, the investigators were able to trace the transit of intravenously administered carbon nanotubes through the bloodstream using the technique of gamma scintigraphy. They found that whilst the modified carbon nanotubes were detected in organs soon after administration, the tubes were also quickly eliminated from the organs. Moreover, urine excretion analysis revealed that the nanotubes were eventually eliminated intact. These results indicating the safety of modified carbon nanotubes provide great promise for their further development as medical tools.
“The field of nanotechnology has been struggling in the last few years to demonstrate that carbon nanotubes can be made safe, which would allow for their beneficial use in a variety of applications,” said Kostarelos. “We hope that our results will provide hope in the search for a new generation of safe and effective medical therapies. The next stage of our work will be to investigate ways of controlling the length of time that these nanotubes remain in the body, to allow them to carry out their work before they are excreted.”
The work on synthesizing water-soluble carbon nanotubes is detailed in a paper titled, “Rapidly functionalized, water-dispersed carbon nanotubes at high concentration.” An abstract is available through PubMed.
The work on biodistribution of water-soluble carbon nanotubes is detailed in a paper titled, “Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers.” Investigators from the Centre National de al Recherche Scientifique (CNRS) in Strasbourg, France, and the University of Trieste in Italy, participated in this study.