Nanoworms detect and fight cancer inside the body

Scientists in the United States have developed 'nanoworms' on a nanometer scale, which are able to swim in the bloodstream, target tumors and evade the body's immune system

One of the great visions of nanotechnology is that the day will come when we can inject nanosubmarines into the bloodstream. The nano-submarines, which will be one-tenth or one-hundredth the size of a human cell, will be able to locate cancer cells and kill them effectively. In the science fiction films and the imaginative paintings about the age of nanotechnology, the artists always imagine the nanosubmarines as sophisticated machines reminiscent of the satellites in outer space. They have a defined geometric shape, and are usually equipped with radar, rake paws, propellers, a cell phone and any other mechanical gadget that the artist aspires to add to the image. The biologists and chemists who have to invent and work with the nanosubmarines that exist today like to scoff at the wild imagination of those craftsmen. The most sophisticated nano-submarines to date were made of liposomes - a kind of tiny soap bubbles that change their shape from moment to moment, and are not at all similar to the nano-submarines described in science fiction and art.

But it is possible that it was the artists who scored this time. Scientists from the University of San Diego, the University of Santa Barbara and the Massachusetts Institute of Technology have developed a new version of nanosubmarines that resemble tiny worms that wriggle through the bloodstream. But why worms?

"The body's defense mechanisms recognize most nanoparticles, capture them and remove them from the bloodstream within a few minutes," explains Michael Saylor, head of the study and professor of chemistry and biochemistry at the University of San Diego. "The reason these worms manage to work so well is as a result of the combination of their shape and a polymer coating on their surface, which allows them to evade the automatic natural elimination processes. As a result, our nanoworms can move around a mouse's body for many hours."

The researchers assembled the nanoworms from spherical nanoparticles of iron oxide, which are able to connect to each other similar to segments of diarrhea. Together they form tiny worm-like structures, 30 nanometers long. These worms are about three million times smaller than normal worms. Since they are made of iron-oxide, they are easy to distinguish in medical imaging devices, and especially in the MRI device, which is used, among other things, to find tumors.

How do the nanoworms target tumors in the body? In order to make sure that the worms will mainly reach the tumors, the researchers coated the worms with a unique molecule capable of binding to cancer cells - a protein called F3. This protein was developed in the laboratory of Arki Ruoslati, a professor and biologist at the University of Santa Barbara. This protein ensures that the nanoworms can bind specifically to the tumor area.

"Because of their elongated shape, the nanoworms can carry many F3 molecules that stick to the surface of the tumor," Saylor says. "This effect, of cooperation between the molecules, improves the ability of the nanoworms to adhere to the tumor."

In order to verify the ability of the nanoworms to identify and adhere to tumors, the scientists injected the worms into the bloodstream of mice with tumors, and followed their movement in the body. They found that the nanoworms do accumulate in the tumors and are even able to stay inside the tumors for up to 48 hours. The accumulation of worms in the mouse's body allowed the researchers to clearly see the location of the tumors. The worms even managed to remain in the bloodstream for many hours, while spherical nanoparticles of a similar diameter were removed from the body by the immune system.

"This is an important feature, because the longer the nanoworms stay in the blood, the more likely they are to hit their targets - the tumors," says Ji-Ho Park, a San Diego State University graduate student in materials engineering who works in Saylor's lab. It was Park who accidentally discovered that the nanoworms are able to stay in the bloodstream for hours, despite their size.

Although the researchers are still not sure why the nanoworms are able to remain in the blood while the nanospheres are removed from it, Park believes that, "the flexible, one-dimensional structure of the nanoworm may be one of the reasons for its long lifetime in the bloodstream."

Despite the good results, it is clear that there is still room for improvement in the existing planning. The nanoworms also tend to accumulate to a large extent in the liver, and because of this they cannot be optimal carriers for anti-cancer toxins at this stage of the research. In order to deal with this problem, among other things, researchers are currently working on new ways to attach different molecules to nanoworms, which will allow them to be more selective about the organs they 'choose' to reach.

"We are now using nanoworms to assemble the next generation of smart nanodevices that are able to focus on tumors," Ruoslati summarizes the research and adds that, "we hope that these devices will improve the diagnostic imaging of cancer, and enable targeted and precise treatment of cancerous tumors."

Other researchers who were involved in the research and development of the nanoworms are Michael Schwartz of the University of San Diego, Sangeeta Bhatia, a physician, bioengineer and professor of health sciences and Geoffrey von Maltzan of the Massachusetts Institute of Technology and Lianglin Zhang of the University of Santa Barbara.

For information on the website of the University of California at San Diego