Oct 28, 2004

Tumbleweeds in the Bloodstream


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Molecule-size sensors inside astronauts' cells could warn of health impacts from space radiation.





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October 28, 2004: Wouldn't it be nice if the cells in your body would simply tell you when you're starting to get sick, long before symptoms appear? Or alert you when a tumor is growing, while it's still microscopic and harmless?


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The ability to detect changes inside of individual cells while those cells are still inside your body would be a boon to medicine. NASA-supported scientists are developing a technology right now that could, if it works, do exactly that.


The scientists don't actually coax the cells into talking, of course. The idea is to place "nanoparticles" inside the cells to function as molecule-size sensors. Whenever these sensors encounter certain signs of trouble -- a fragment of an invading virus perhaps -- they would begin to glow, signaling the outside world that something is wrong.

Right: Computer-generated images of nanoparticles. Image courtesy Center for Biologic Nanotechnology, University of Michigan-Ann Arbor. [More]

It's an elegant technology, and because it can be customized to target many combinations of specific cell types and specific problems, it's also a very potent one. Research on nanoparticles has blossomed in recent years, with scientists exploring how they can be used to treat everything from cancer to genetic diseases such as cystic fibrosis.




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NASA is interested in how this technology might help tackle another health issue: radiation exposure.

One of the main hurdles for a mission to Mars is the radiation dose that astronauts would receive during their 6-month journey there. The spaceship would be shielded, but the best radiation shields NASA has now might not fully protect the astronauts. (See: "Can People Go to Mars?")

So scientists are looking for medical ways to monitor, prevent, and repair the ill effects of radiation. To make the challenge even harder, these solutions must work well in space, where astronauts must be able to treat themselves, and where there's little spare room for bulky medical equipment.

James Baker, director of the Center for Biologic Nanotechnology at the University of Michigan, believes that nanoparticles can help. His research group has received a grant from NASA to look into it. "Nanoparticles let us monitor the actual biological impact of radiation on the astronauts' bodies, which is more meaningful than simply measuring the radiation itself," Baker explains.


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Above: Nanoparticles are larger than typical molecules but smaller than viruses. (They're labeled "nanoscopic" in this diagram). They're similar in size to many proteins, which is part of the reason the can operate well inside of cells. Image courtesy University of Michigan-Ann Arbor.

Picture this: Before a space mission, an astronaut uses a hypodermic needle to inject a clear fluid, laced with nanoparticles, into his bloodstream. During flight, he puts a small device in his ear. This device, shaped like a hearing aide, uses a tiny laser to count glowing cells as they flow through capillaries in the eardrum. A wireless link relays those data to the spaceship's main computer for processing.

This sci-fi scenario is still at least 5 to 10 years away, but a lot of the necessary pieces are already taking shape in the laboratory.

That clear fluid injected into the astronaut's bloodstream would contain millions of microscopic nanoparticles. The nanoparticles themselves are nothing new: Scientists have been using them in the laboratory for at least 5 years, and they have employed them safely in lab animals.

The particular kind of nanoparticle that Baker uses resembles tumbleweed: a little ball-shaped bundle of branching "twigs" growing out from a central point.


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By itself, this tumbleweed is inert. (That's good: it means it's not toxic.) It only serves as a generic platform upon which to build. All the useful functions of the nanoparticle -- seeking out the right kind of cells, detecting signs of radiation damage, offering up a fluorescent "red flag" -- come from molecules attached onto this scaffolding. The free ends of the twigs provide lots of binding points where these molecules can be attached (128 locations with the nanoparticles Baker's group uses).


Right: The nanoparticles that Baker's group uses are called "dendrimers," and are built up by adding branching segments around a central core. Image courtesy University of Michigan-Ann Arbor. [More]

Choosing which molecules to attach is how scientists customize the nanoparticle to do their bidding. For example, Baker's group wants to tweak their nanoparticles to enter a kind of white blood cell called a lymphocyte, which is especially sensitive to radiation.

"How do we specifically target lymphocytes?" asks Thommey Thomas, a research assistant professor on Baker's team. "Because once you inject nanoparticles into the bloodstream they can go anywhere, right?"

"We had to find some specific targeting molecules on the surface of these lymphocytes," he explains.

All of the body's cells naturally have "receptor" molecules embedded on their outer surfaces. These receptors control which chemicals can enter the cell: for example, a kidney hormone in the bloodstream only enters kidney cells. By attaching a molecule to their nanoparticles that matches up with a specific receptor on lymphocytes, the researchers assure that these roaming nanoparticles wind up inside only the right cells.


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Left: James Baker, director of the Center for Biologic Nanotechnology at the University of Michigan. [More]


Once inside the lymphocytes, nanoparticles need a way to detect radiation damage. One way is to watch for signs that the cell is about to self-destruct. Lymphocytes commit cellular suicide (called "apoptosis") when they've been damaged by radiation. This is a genetically programmed behavior carried out by special "suicide" enzymes. Baker's group has discovered how to attach to the nanoparticles a fluorescent dye molecule that reacts to these suicide enzymes. Lymphocytes beginning to self-destruct due to radiation damage would glow.

The research group has also developed a laser system to count the glowing cells. They've already shown that it can count cells in a mouse's bloodstream as those cells pass through the capillaries in its ear, but Baker says it's still too early to know what form this laser system would take for a space mission--maybe a micro-laser integrated into a hearing-aide-like device, he speculates.

The net result: continuous, real-time monitoring of radiation damage to the cells in an astronaut's bloodstream -- no bulky medical equipment required.