Editorial Article
Monday November 30, 2009
by Caitlin Smith
Nanotechnology: the science of small. Can you imagine nanocars that drive with rotating buckyball wheels, delivering drugs or other reagents to specific parts of your brain? Though this isn’t possible yet, it is a scenario whose time will come. Already, nanotechnology researchers can design roadmaps on a DNA scale, and particles that can circulate in blood and hunt down cancer cells. Nanotechnology’s applications are only just emerging: here are some recent advances in the world of the small but mighty.
Three-dimensional creations
While DNA is primarily thought of as information to be decoded, some researchers at Caltech saw it also as a physical support structure on which they could hang tiny things like carbon nanotubes. Si-ping Han, senior graduate student in the lab of William Goddard at Caltech, is investigating the use of DNA as a scaffold structure upon which devices can self-assemble. “I work at the intersection between structural DNA nanotechnology and nanoelectronic device self-assembly,” he says. The rich information content of DNA molecules makes it particularly attractive as a scaffold for synthetic materials such as carbon nanotubes, which are rolls of a hexagonal mesh of carbon atoms. Carbon nanotubes are notoriously difficult to arrange. Han and members of three other labs at Caltech applied the new technique of DNA origami to the arrangement of carbon nanotubes, showing promise for the construction of nanoscale electronic devices.1 In DNA origami, longer single strands of viral DNA are mixed with different short synthetic strands used to bind the longer DNA into nearly any shape. The work of Han and others showed the ability of carbon nanotubes to stick to the “maps” constructed with DNA origami.
Han notes some other recent advances in three-dimensional nanoscale work. William Hsieh’s lab at Harvard University has advanced DNA origami technology to create complex three-dimensional objects, and made engineering the objects easier with new design software and TEM methodology. Decades of work in Ned Seeman’s lab at New York University have resulted in the ability to design and grow crystals of a nanoscopic-sized three-dimensional triangular DNA lattice. “This is an amazing achievement because any minor structural flaw or distortion tends to get propagated and amplified during crystal growth,” says Han. “The perfection of these new crystals represents a new level of understanding and control over the properties of DNA nanostructures.”
A role in energy conservation
In the world of tiny volumes of fluids, nanofluidic devices have miniaturized experiments, reduced reagents needed, and minimized sample loss and errors. Wouter Sparreboom, a post-doc in the BIOS Lab-on-a-Chip group at the University of Twente in the Netherlands, studies the “nanofluidic devices with integrated electrodes for flow control and sensing purposes.” Besides the benefits of nanofluidic devices already enjoyed by researchers today, Sparreboom says that they are investigating the use of nanofluidics in energy conservation. An exciting development in this field, he says, is “energy generation via streaming potential in systems with liquid slip, since a possible advent of an energy crisis requires the development of new sources of energy. Here, nanotechnology might offer a very space-efficient solution because of its small footprint, and therefore high power density.”
According to Sparreboom, the biggest challenge facing nanofluidics is the inherent problems introduced by the enormous surface-to-volume ratios in nanofluidic systems, such as “understanding and control of adsorption of molecules to the surface, which may lead to large losses and a change in surface properties,” he says. “Precise control in surface properties becomes important, which [can, for example, be accomplished] by coating or chemical modification of the surface.” Sparreboom predicts that future developments will include better control of surface properties, in addition to more applications in energy conversion, biochemistry and analytical chemistry.
Nanotechnology in medical applications
The use of nanotechnology in medical applications is emerging with exciting new developments barely imaginable a few decades ago. NanoString Technologies will soon enter the field of molecular diagnostics with their digital barcoding system that directly detects and counts single molecules in biological samples. Their nCounter Analysis System can profile individual molecules in multiplexed reactions without amplification. “While gene expression profiling is our first commercially supported application, the underlying NanoString technology can support a wide range of direct digital molecule profiling applications,” says Lianne McLean, vice president of marketing. “We are now in the process of developing the technology for miRNA profiling and Copy Number Variation detection.”
The National Cancer Institute core labs have recently adopted NanoString’s technology, and the Broad Institute has entered a three-year research collaboration with NanoString. “We are excited about the ability of our technology to revolutionize molecular diagnostics by making it fast, simple and cost effective to survey the expression of hundreds of genes in a single tube at one time,” says McLean. “Molecular diagnostics is the fastest growing segment of the diagnostics market, and we believe nanotechnology has an important role to play in making personalized medicine a reality.”
The use of nanoparticles in anti-cancer applications is showing great promise. Vladimir Zharov, professor of biomedical engineering at the University of Arkansas for Medical Sciences, and director of the Phillips Classic Laser and Nanomedicine Laboratories in the the Winthrop P. Rockefeller Cancer Institute, has developed nanoparticles that absorb strongly in the near-infrared region (to which most tissues are transparent). “Targeting of tumor cells with strongly near-infrared absorbing nanoparticles could allow both highly sensitive diagnosis and targeted killing of individual tumor cells noninvasively in deep tissue (using deeper laser penetration with minimal attenuation), which is safe for surrounding healthy tissue,” says Zharov.
In a recent paper,2 Zharov’s group showed that they can magnetically capture tumor cells circulating in blood vessels (a common indicator of metastasis) using magnetic nanoparticles in the bloodstream, “followed by rapid photoacoustic detection using dual magnetic-photoacoustic flow cytometry technology,” says Zharov. “The use of the golden carbon nanotubes as a second contrast agent for photoacoustic imaging substantially improved detection sensitivity and specificity. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification, and multicolor recognition, our approach allows circulating tumor cells to be concentrated from a large volume of blood in the vessels of tumor-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans.” In another paper,3 Zharov’s group showed “molecular detection of lymphatic endothelial cells and targeted destruction of lymphatic wall in vivo using bioconjugated golden carbon nanotubes. This holds promise for mapping and destruction of intra- or/and peri-tumor lymph vessels that provide initial dissemination of detached tumor cells to metastatic sites,” says Zharov.
Zharov’s technology has been approved for pilot studies in humans ex vivo, and is now under investigation for use in vivo. He hopes to expand his investigations to include further research into the biology of lymphatics. “Many questions on lymphatic functions remain unanswered, including in vivo control of lymphangiogenesis and ways to track and eradicate metastatic cells in prenodal lymphatics and the sentinel lymph nodes,” he says. “Novel nanoparticles and their various hybrids may be used for a variety of biomedical applications including non-invasive and highly target-specific lymphatic diagnosis and therapy as well as treatment of tumors and infections.” In addition to cancer treatments, nanoparticles may also one day be used for detecting and treating cardiovascular problems or bacterial infections. It seems fitting that one day we may be able to counter-attack tiny agents such as harmful bacteria or tumor cells with our own nanodefenses—small but mightier and smarter.
References
1 Nature Nanotechnology (2009) Nov 8 Epub ahead of print.
2 Nature Nanotechnology (2009) Nov 15 Epub ahead of print.
3 Nature Nanotechnology (2009) 4: 688-694.