Last updated April 18, 2018 at 9:21 am
Like a microscopic Rambo, they hunt down and attack tumours
It sounds like science fiction, but scientists from the US and China have built nanorobots 1,000 times smaller than a human hair, that move around the body on a cancer seek and destroy mission.
Completely autonomously, they travel through blood vessels looking for tumours, and then cut off their blood supply, effectively choking them to death.
This genius approach has been used in mammals for the first time to shrink breast cancer, melanoma, ovarian and lung cancers in mice. However, the researchers say it could be used for nearly any type of solid-tumour cancers.
This is potentially a huge development.
Seek and destroy
“We have developed the first fully autonomous, DNA robotic system for … targeted cancer therapy,” said Hao Yan, who led the research team at Arizona State University.
The DNA sheet with thrombin attached. Credit: Jason Drees, Arizona State University
The secret lies in the use of DNA origami. Just like Japanese paper folding creating intricate shapes, the researchers created tiny structures out of DNA which can be fold into complex shapes one thousand times smaller than a human hair.
The researchers first created tiny sheets of DNA measuring only 90 nanometres by 60 nanometres in size. To this flat sheet they attached thrombin, a molecule which causes blood clots to form.
The DNA sheet was then rolled up into a tube with the thrombin protected on the inside. These tubes could then be injected into the blood stream of the mouse.
The rolled nanorobot, containing thrombin inside and DNA aptamers on the surface. The DNA aptamer could specifically target a protein, called nucleolin. Credit: Jason Drees, Arizona State University
As the DNA origami tubes travelled through the mouse’s blood they were on the lookout for nucleolin, a protein that is made in high amounts only on the surface of blood vessels leading to tumours – and importantly not found on the surface of normal blood vessels or healthy cells.
When the DNA origami tube located nucleolin, it locked onto it using a special structure called a DNA aptamer. Once secured, the tube unrolled itself, releasing the thrombin like a cancer-killing trojan horse.
The freed thrombin then set to work creating a blood clot leading to the tumour, quickly cutting off its blood supply and starving the tumour to death.
Working in numbers, the nanorobots could quickly surround the tumour just hours after injection – all without any outside assistance.
Safe killing machines
“These nanorobots can be programmed to transport molecular payloads and cause on-site tumour blood supply blockages, which can lead to tissue death and shrink the tumour,” said Baoquan Ding, from the Chinese Academy of Sciences, who was also involved in the research.
During experiments in mice tumours began being affected within 24 hours of injection with nanorobots, and within 3 days all the tumour types had blood clots surrounding them.
When used to treat mice with human melanoma, 3 out of 8 the mice receiving the nanorobot therapy showed complete regression of the tumours. The life expectancy of the mice also more than doubled, from 20.5 days to 45.
The clots in the blood vessels created by the nanorobots also prevented the melanoma from metastasizing, or spreading to other locations the body.
The researches also tried their system in a test of a mouse lung cancer model, which mimics the progression of lung cancer in humans. After 2 weeks of treatment they found the tumours had shrunk.
One of the difficulties of cancer treatments is specificity – attacking the cancerous cells without affecting normal cells in the body.
The nanorobots however were completely safe to non-cancerous cells. They weren’t recognised by the immune system as foreign, and so avoided causing an immune reaction. They also didn’t affect normal calls, or increase blood clotting anywhere else in the body.
Most importantly, the nanorobots didn’t spread into the brain where they could cause unwanted side effects, such as a stroke.
After attacking tumours, most of the nanorobots were cleared and degraded from the body after 24 hours.
The path to making small, big
Nanomedicine is a new branch of medicine that uses nanotechnology to open up new ways to treat disease.
This project began around 5 years ago when the Chinese researchers at the National Center for Nanoscience and Technology wanted to specifically cut-off of tumour blood supply by inducing blood coagulation. The Arizona State University team were experts in making nanostructures “programmable”, by adding the structures which allowed the nanorobot to perform missions entirely on its own.
“The thrombin delivery DNA nanorobot constitutes a major advance in the application of DNA nanotechnology for cancer therapy,” said Yan, leader of the Arizona team. “In a melanoma mouse model, the nanorobot not only affected the primary tumour but also prevented the formation of metastasis, showing promising therapeutic potential.”
The study so far was carried out in mice and miniature pigs, so it will need to be studied for efficacy and safety in humans before being available to the general public.
“I think we are much closer to real, practical medical applications of the technology,” said Yan. “Combinations of different rationally designed nanorobots carrying various agents may help to accomplish the ultimate goal of cancer research: the eradication of solid tumours and vascularized metastases.”
However, they also see the strategy as useful for more than just cancer treatment. “Furthermore, the current strategy may be developed as a drug delivery platform for the treatment of other diseases by modification of the geometry of the nanostructures, the targeting groups and the loaded cargoes,” Yan added.
The study has been published in Nature Biotechnology
Video animation by Jason Drees, Arizona State University
