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Fantastic Voyage - Nanotechnology

Scientists are crafting microscopic vessels that can venture into the human body and repair problems €“ one cell at a time.

by Patrick Barry

It's like a scene from the movie Fantastic Voyage. A tiny vessel - far smaller than a human cell - tumbles through a patient's bloodstream, hunting down diseased cells and penetrating their membranes to deliver precise doses of medicines. 

Only this isn't Hollywood. This is real science.

Researchers funded by a grant from NASA recently began a project to make this futuristic scenario a reality. If successful, the "vessels" developed by these scientists - called nanoparticles or nanocapsules - could help make another science fiction story come true: human exploration of Mars and other long-term habitation of space.

While space applications will be the researchers' primary focus, nanoparticles also hold great potential for many fields of medicine, particularly cancer treatment. The tantalizing promise of delivering tumor-killing poisons directly to cancerous cells, thus averting the ravaging side-effects of chemotherapy, has generated a lot of interest in nanoparticles among the medical community.

"The purpose of these nanoparticles is to introduce a new type of therapy - to actually go inside individual cells ... and repair them, or, if there's a lot of damage, to get rid of those cells," explains James Leary of the University of Texas Medical Branch. Leary is leading the research along with Stephen Lloyd, and Massoud Motamedi, also from the University of Texas; Nicholas Kotov of Oklahoma State University; and Yuri Lvov of Louisiana Tech University.

Copyright 1999, Daniel Higgins, University of Illinois at Chicago.

Tiny capsules much smaller than these blood cells may someday be injected into people's bloodstreams to treat conditions ranging from cancer to radiation damage.

Their project will focus on a problem related to cancer - the high radiation doses experienced by astronauts in space, especially on journeys to the Moon or to Mars, which require leaving the protective umbrella of the giant magnetic field surrounding the Earth.

Image courtesy NASA/OBPR.

High-energy cosmic radiation can cause damage DNA and make cells behave erratically.

Even the advanced materials used for radiation shielding on spacecraft can't fully insulate astronauts from the high-energy radiation of space. These photons and particles pierce the astronauts' bodies like infinitesimal bullets, blasting apart molecules in their path. When DNA is damaged by this radiation, cells can behave erratically, sometimes leading to cancers.

"This is an important problem," Leary says. "If humans are going to live in space, we have to figure out how to protect them from radiation better."

Because shielding alone probably won't solve the problem, scientists must find some way to make the astronauts themselves more resistant to radiation damage.

Nanoparticles offer an elegant solution. These drug-delivery capsules are tiny - only a few hundred nanometers, which is smaller than a bacterium and smaller even than the wavelengths of visible light. (A nanometer is one-millionth of a millimeter.)

A simple injection with a hypodermic needle can release thousands or millions of these capsules into a person's bloodstream. Once there, nanoparticles will take advantage of the body's natural cellular signaling system to find radiation-damaged cells.

The trillions of cells in a human body identify themselves and communicate with each other via complex molecules embedded in their outer membranes. These molecules act as chemical "flags" for communicating to other cells or as chemical "gates" that control entrance to the cell for molecules in the bloodstream (such as hormones).

Image copyright Scott Barrows, University of Illinois at Chicago.

A two-layered membrane separates the cell interior in the bottom-right of this image from the surrounding environment. Complex molecules in this outer membrane control how the underlying cell interacts with its surroundings.

When cells become damaged by radiation, they produce markers in a particular class of proteins called "CD-95" and place these on their outer surfaces.

"It's how the cell speaks to other cells and says, 'Hey, I'm injured,'" Leary says.

By implanting molecules in the outer surface of the nanoparticles that bind to these CD-95 markers, scientists can "program" the nanoparticles to seek out these radiation-damaged cells.

If the radiation damage is very bad, nanoparticles can enter the damaged cells and release enzymes that initiate the cell's "auto-destruct sequence," known as apoptosis. Otherwise, they can release DNA-repair enzymes to try to fix the cell and return it to normal functioning. 

Humans and other organisms have natural enzymes that tend to DNA and repair mistakes, but some do a better job than others. "There are organisms that can [absorb high] radiation doses and do just fine," Leary says. By studying such species, scientists have already fashioned DNA-repairing enzymes that could be delivered by nanoparticles.

Leary's team is also studying ways to attach fluorescent molecules to the nanoparticles. These could be designed to light up at certain stages of the process, even employing different colors for different stages. These fluorescent tags would provide a way to monitor the nanoparticles within the body.

"To assess the degree of radiation damage, an astronaut would put on something like a pair of glasses, but those glasses peer inward onto the retina," Leary explains. "And you use the flowing of [fluorescent] nanoparticles on cells through the retina as sort of an in vivo assessment instrument." (In vivo means "within the organism.")

Related technology already exists - it's used to measure blood flow changes in the retina due to various diseases. NASA is interested in such non-invasive ways to monitor health because astronauts might need to act as their own doctors on extended missions.

Courtesy Yuri Lvov, Louisiana Tech University.

In this illustration nanocapsule walls are partially dissolved, then allowed to reform, trapping fluorescent-tagged drug molecules inside. Such vessels can be made of self-assembling polymers or of semiconductor materials such as cadmium telluride.

"Eventually, astronauts might wear these glasses to sample what's going on in their bloodstream. And then if they need treatment, they have a hypodermic needle with the appropriate nanoparticles for the job," he says.

Nanoparticles are a radically new approach to biosensing and medicine delivery, and as such the technology will require many more years to become mature and dependable. But it's not a pie-in-the-sky fantasy. All the elements of this idea have already been demonstrated separately - the DNA-repair enzymes, the nanoparticles, the fluorescent tags. The trick is getting them all to work together reliably.

"This is a very difficult problem, and we're not going to be able to do it all in three years," which is the duration of the grant. "We're trying to do some pretty innovative science here - it's a bit of a jump," says Leary. "But that's why it's a lot of fun to work on."


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First Science 2014