Tiny treatments promise big results
In the future, diagnosing and treating cancers could be much more specific and effective if the predicted benefits of nanotechnology are realized. Nanotechnology, which deals with materials that are of the order of a few billionths of a meter in size, promises to help image specific parts of the human body more effectively or enable physicians to deliver drugs more precisely to the places where they are needed.
All around the world, research teams are busy developing and testing these tiny particles -- whether based on carbon nanotubes, polymers, inorganic semiconductors or metals -- for a wide range of applications.
This range is reflected in the conference programs of SPIE's BiOS 2008 symposium, part of Photonics West. Research presented at this meeting included imaging, laser therapy and photo-induced drug delivery - all at the nanoscale. And the range of potential applications for these techniques is wide. Tagging particular parts of the body with nanoparticles could help with anything from basic understanding of the behavior of protein membranes to adjusting temperatures in the body to help with laser therapy or radiation treatment. There is also plenty of research going on into how to fabricate quantum dots and other nanoparticles and how to functionalize them to be compatible with the human body.
Much of the current work in bionanophotonics focuses on imaging. Nanoparticles offer huge potential benefits to imaging tissue in humans, as well as to monitoring the effects of medical trials on animals, for example, without having to kill the animal.
Techniques such as optical coherence tomography (OCT) work by looking for contrast in the way that light is scattered but, inevitably, the scattering from a piece of healthy tissue is not very different from that of another piece of tissue that might be diseased. Dirk Faber, one of the speakers at BiOS, believes that nanoparticles hold the key to improving this contrast and increasing the resolution of the technique so that tissue can be imaged at the cellular or even molecular level. "Adding molecular information would make OCT a very powerful technique," he pointed out.
Faber and his colleagues at the University of Amsterdam and Massachusetts General Hospital, are researching nanoparticle-assisted optical molecular imaging (NAOMI) using biodegradable nanoparticles as well as systems containing gold nanoparticles. "The advantages of nanoparticles are that you can bind them to anything you want to and they can be designed to have really good contrast. You can't do this with fluorophores, for example. They just fluoresce at certain wavelengths," Faber explained.
He added that the scale is also important because nanoparticles are big enough to be imaged by the technique. "It has to have some size. If you could use OCT to look at the molecular level then you could image cells directly," he said.
The potential applications of using nanoparticles to enhance imaging are already being investigated. For example, Amy Oldenburg and colleagues at the University of Illinois at Urbana-Champaign and Purdue University, have found that plasmon-resonant gold nanorods provide spectroscopic OCT contrast in removed human breast tumors. This has future application toward in vivo molecular imaging using surface-functionalized nanorods, believe the researchers, who presented this research at BiOS.
A similar idea promises to help in the early detection of prostate cancer, according to a recent paper in the Journal of Appied Physics Researchers at University of Michigan have reported using plasmon-resonant gold nanorods to enhance the contrast in photoacoustic imaging.
But nanoparticle-assisted imaging is not only expected to help understand diseases better. It could also help to study nanoparticles themselves. "The reality is that we don't know much about nanoparticles in biology yet. One of the reasons is that we don't have the tools to image them," pointed out the University of Amsterdam's Faber.
Another speaker at BiOS, Dennis Matthews, who is director of the NSF Center for Biophotonics and a professor in the Department of Neurological surgery at University of California, Davis, agrees about the importance of this. Research at his center includes imaging biomolecules by X-ray diffraction and studying drugs in the body using surface-enhanced Raman spectroscopy. "It is very important to have these sorts of techniques to study quantum dots and other nanoparticles," he said.
Being able to study such materials is important because many research groups around the world are looking to nanoparticles to not just for monitoring but also for treating diseases. Matthews believes that nanoparticles could be particularly useful where a specific part of the body needs to be targeted in treating an inflammatory disease, for example. "They can be made extremely specific," he said. "They can be designed to be activated by heating, ultrasound, RF radiation or light to, for example, break apart and release drugs. They can also be used to both apply and monitor treatment."
Such characteristics could also help in cancer treatment, for example after a brain tumor has been removed. "After neurosurgeons remove a tumor from the brain the areas around where the tumor was removed from are more susceptible to developing further cancers," said Matthews. "If we can inject suitable nanoparticles into the area surrounding the site of the tumor then we can monitor them and administer treatment if required. This could reduce the need for further surgery or more general treatments such as chemotherapy or radiotheraphy. More specific therapy improves the outcome for the patient."
It's not just research groups that are looking at the biological applications of nanoparticles. It's big business too. According to a recent study by BCC Research, biomedical applications of nanotechnology were worth an estimated $129.5 million in 2007 and this market is expected to grow to $519.5 million in 2012. There are hundreds of products on the market that claim to be based on nanotechnology, and this includes medical products.
Fixed and permeabilized HeLa cells were labeled with mouse anti-α-tubulin primary antibody and 20nM Qdot 625 goat anti-mouse IgG. Photo: Invitrogen Corporation.
One example is US-based Invitrogen, which two years ago complemented its fluorescence-based labeling and detection product base by acquiring quantum-dot technology. According toSteve Chamberlain, the company's senior product manager for labeling and detection,"Our Qdot nanocrystals provide several advantages compared to traditional dyes." The biggest of these advantages are "their exceptional photostability, which means that the signal can be detected for very long periods of time under continuous illumination without fading," and "their ability to perform multispectral analysis with a single excitation source due to the unique light-absorbing characteristics of the quantum dots." He added that the company can make chemically stable, water-soluble quantum dots that have an extremely long shelf life, and are biofunctionalized by covalently conjugating to them biomolecules.
However, despite the considerable research activity, both in labs and in commercial companies, there are still questions to be answered before nanotechnology can really take off, especially in medical applications. The biggest of these concerns a lack of knowledge about whether nanoparticles are toxic. And, unlike many new technologies, such fears are actually being driven by scientists more than by the general public. A recent report in the journal Nature Nanotechnology revealed that more than 30 percent of the 363 leading US nanotechnology scientists and engineers polled expressed concern that human health may be at risk from the technology. In contrast, only 20 percent of the public held such fears. Similarly, concerns over possible nanotechnology pollution were greater among the scientists than the public.
Such uncertainties arise because the properties of materials can drastically change when they are very small compared with those of a bulk material: most of the reactions occur on the surfaces of materials so the effect of increasing the surface-to-volume ratio could be dramatic. In a paper in Nature last year, nanotechnology expert Andrew Maynard set the industry five challenges to investigate these concerns and "stimulate research that is imaginative, innovative and above all relevant to the safety of nanotechnology." These challenges include developing instrumentation to assess exposure to nanoparticles; developing methods to evaluate their toxicity and environmental impact; and developing models to predict such risks.
Government organizations do seem to be heeding such concerns and warnings, though critics might argue that more is required. In the US last year, for example, it was estimated that the agencies making up the National Nanotechnology Initiative collectively funded $67 million of research into improving understanding of the potential impacts of human health, the environment and work-based exposure to nanoparticles.
Research in this area is also going on commercially. "The questions being raised are valid ones. We are devoting considerable resources to gain a better understanding of the toxicity potential of these materials," said Invitrogen'sChamberlain. "We engage independent testing agencies to perform both in-vitro and in-vivo testing to help determine what impacts such materials may have on living systems."
There are huge benefits for the whole industry to gain from answering such questions. If more nanoparticles are approved for use in humans then we could see dramatic improvements in the ways that very serious diseases are diagnosed and treated -- provided that the nanoparticles do not bring fresh problems with them.
