Nearly 1.7 million new cases of cancer are detected in the United States each year, and each year cancer claims almost 600,000 lives in the U.S. alone, making it the second-leading cause of death nationally. Treatment is sometimes worse than the illness, as invasive surgeries can be traumatic, and chemotherapy can cause off-target effects that wreak havoc on the entire body. But a new technique described in Nature Biotechnology, which uses nanorobots — literally microscopic robots — to specifically target tumors and cut off their blood supply has the potential to change treatment forever.

In the paper, published in February, an international team of scientists demonstrated the effectiveness of using DNA nanorobots to attack tumors in mice and pigs with cancer. These nanometer-sized robots are made of DNA that unfolds itself at precisely the right time and place to deliver a drug to only the exact target in the body. The DNA, folded up like an origami package, held molecules of thrombin, an enzyme that makes blood clot.

DNA origami nanorobot
When this DNA origami nanorobot detects blood vessels associated with tumors, it opens up to deliver thrombin, a clotting factor that chokes off the blood supply to the tumor.

To test whether this novel drug delivery system works, the team of scientists from Arizona State University and the National Center for Nanoscience and Technology of the Chinese Academy of Sciences injected the nanorobots into the bloodstreams of mice with tumors. They found that the treatment effectively targeted tumors, stopping their growth and even initiating tumor death.

Stopping tumor growth isn’t enough to prove the drug works, though, as it must also prove itself safe. So, the researchers also injected the nanorobots into the bloodstreams of Bama miniature pigs, which have been shown to be good models for testing preliminary drug safety for humans. One major concern with nanorobots is that they could get into the brain and cause strokes, but this did not happen with the test subject animals.

The nanorobots open up to deliver thrombin to the blood vessels that feed the tumor.
When they detect proteins associated with cancer cells, the nanorobots open up to deliver thrombin to the blood vessels that feed the tumor.

The precision of the nanorobots, which is what makes their potential for safe cancer treatment so great, is due to their meticulously crafted structure. The drug-holding “package” is made up of DNA sheets, measuring 60 by 90 nanometers, that wrap around thrombin molecules. On the outside of the folded sheets are molecules that zero in on nucleolin, a protein that’s present in the lining of blood vessels associated with growing tumors.

These molecules, called aptamers, both target the proper spot to deliver drugs and actually open up the DNA sheet up to expose the thrombin when the nanorobot finds the right spot. In theory, when the thrombin is released, it clots the blood entering the tumor, thereby starving it of the oxygen it needs to grow. This method, which essentially strangles the tumor, is reminiscent of the class of cancer drugs known as angiogenesis inhibitors, which help inhibit the growth of blood vessels that feed tumors.

These nanorobots show great promise, but they aren’t ready for humans yet. To get there, the researchers are seeking out clinical partners to further develop this treatment pathway. Still, the fact that it seems to work in mice and pigs makes it likely that nanorobots like these will be available as cancer treatments within our lifetimes.

Abstract: Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.