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Still in its infancy in Minnesota, nanobiotechnology has already taken more than its first few steps.
Quantum dots. Stealth liposomes. Nanogold. The terms have the ring of science fiction.
But they’re quickly becoming part of the lexicon of a growing number of biomedical researchers at the University of Minnesota and Mayo Clinic who are attempting to make the state a player in the burgeoning field of nanobiotechnology.
The university’s efforts are headed by Stephen Ekker, Ph.D., an associate professor in the department of genetics, cell biology and development, who is trying to capitalize on the university’s already well-established capabilities in both medicine and nanotechnology—the May/June 2006 issue of Small Times magazine ranked the university ninth in the nation for research.
The U’s Big Leap
Ekker became interested in nanotechnology, the design and production of atomic-, molecular-, or macromolecular-scale particles, while working on a problem in his own lab—trying to find a new method for delivering genes to cells. That led him to talks with colleagues in chemistry and engineering. And those meetings broadened to a series of discussions about the biomedical applications of nanotechnology that included people from throughout the university who worked in information technology, the health sciences, and the biological and physical sciences.
Ekker quickly saw the potential for harnessing his colleagues’ brainpower for nanobiotechnology. And because he holds degrees in electrical engineering as well as molecular biology, he knew that he had a role to play in making it happen. “I was able to serve an important function,” he says now, “as translator.”
The conversations came into focus during the last couple of years as the university applied for National Institutes of Health (NIH) funding to establish a nanotherapy cancer center. “It got things going in terms of people sitting down and saying, ‘Is this possible or not? Is this science fiction or not?’” Ekker says.
One of the projects that surfaced during that process is development of an artificial antigen. “That actually evolved,” he says, “because you put an immunologist, a clinician, a chemist, and an electrical engineer in the same room together to talk about a common problem.” Their challenge was to find a way to make a cancer vaccine from scratch. Ideas that seemed far-fetched to one researcher in one discipline suddenly were thrust into the realm of the possible by another from a different field.
Although the university did not get the NIH dollars to start a nanotherapy cancer center, it did end up with a set of five well-developed projects (see “Nanobiotech at the U,” p. 10) that were lauded by NIH reviewers for their innovation and collaborative nature. On July 1, 2006, the university officially launched its NanoBiotechnology Initiative, which provides seed money and administrative support for research.
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Nanobiotech at the U
Five nanobiotechnology research projects are underway at the University of Minnesota as a result of recent efforts to blend the university’s strengths in IT, the basic sciences, and medicine.
1. Multivalent, antigen- presenting nanoparticles. Investigators from chemistry and immunology are attempting to create an artificial vaccine.
2. Nanoparticle-mediated transposon delivery for colorectal cancer. Investigators from genetics, cell biology and development, and chemical engineering are attempting to make “stealth liposomes” that can be used to deliver therapeutic genes for colorectal cancer.
3. Immunotherapeutic nanorings. Researchers from medicinal chemistry and therapeutic radiology are developing a protein-based nano-scale scaffold for delivering imaging or therapeutic agents.
4. MRI tracking of cell therapy with magnetic nanoparticles. Investigators from medicine and the Center for Magnetic Resonance Research are exploring the use of magnetic core nanoparticles to track the cells introduced in therapies such as stem cell transplants.
5. Nanostructured contrast agent for breast imaging. Investigators from mechanical engineering and medicine are exploring the use of fluorescent nanocrystals called quantum dots as contrast agents in imaging.
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Ekker, who is at the helm of the initiative and describes himself as its “chief cheerleader,” says the exciting thing is that the initiative is up and running at all. Working out the administrative and bureaucratic bugs was a multi-year process that involved getting the blessing of four deans, two provosts, and one vice president.
Ekker believes that if the university is going to be a player in nanobiotechnology it will have to maintain that sort of cooperation. He’s particularly concerned about supporting the community of faculty who have come together around the initiative in recent years. “It’s not often you have engineers that understand problems in cancer,” he says. “That set of scientists is going to be invaluable in the 21st century.”
And he believes the university’s first “deliverables” will likely be imaging agents. For example, one group of researchers is exploring the use of nanocrystals called “quantum dots” as a contrast agent for imaging breast tumors. The particles are nanometer-scale fluorescent semiconductors that can be used to track cells because they fluoresce as a function of their size, producing different colors on images. Another group is exploring whether nanoparticles produced with a magnetic core could be used to track cells in the body via magnetic resonance imaging.
Although it has been a struggle to assemble the disparate participants in the initiative, and although he’s cautious about overstating the promise of nanobiotechnology, Ekker is optimistic that it can thrive at the University of Minnesota. “If we can’t do it here, where you have a world-class cancer center and world-class engineers in IT, and you have units like the Stem Cell Institute … If you can’t do it where everybody is physically within walking distance from one another, where are you going to do it?”
Mayo’s Small Steps
While the University of Minnesota has attempted to leap into nanobiotechnology, researchers at Mayo Clinic have taken smaller steps into the field, with research coming primarily out of one lab and focusing on a few types of nanoparticles.
“This is a bottom-up approach,” says Debabrata Mukhopadhyay, Ph.D., professor of biochemistry and molecular biology and project leader of the tumor angiogenesis, vascular biology, and nanotechnology laboratory, which is examining the potential of gold and other nanoparticles for drug delivery and gene therapy for cancer and cardiovascular diseases.
The lab is staffed by a dozen or so Harvard transplants who have come to Mayo in the last three years to work on vascular modeling. Among them is Priyabrata Mukherjee, Ph.D., an assistant professor of biomedical engineering, who Mukhopadhyay describes as the resident proponent of nanotechnology and the “master” at making different nanoparticles, including nanogold particles that have been shown to inhibit neoangiogenesis by blocking heparin-binding proteins.
Mukhopadhyay says they also have used gold nanoparticles to deliver drugs and other biomolecules to targeted cells in animal models. His group is currently studying their potential in humans with chronic lymphocytic leukemia and other forms of cancer. He says there is “excellent data” that has not yet been published, and the group is exploring the possibility of developing clinical trial–grade nanomaterials with several companies.
Mukhopadhyay acknowledges that Mayo Clinic does not have the nanotech infrastructure that the university does and thus is seeking funding through the Minnesota Partnership for Biotechnology and Medical Genomics for collaboration on several projects. One in the works that clearly blends the two institutions’ separate research capabilities involves tracking gold-coated magnetic-core nanoparticles via imaging.
Like Ekker, Mukhopadhyay is confident about the potential for the new field. “We can do something good,” he says. “I believe strongly that we are heading in the right direction.”—Carmen Peota