Perhaps they are not the robots that come to mind when thinking of Isaac Asimov’s three laws of robotics. But they are designed to follow orders: prevent the blood supply to tumours from stopping their growth. So we are talking about the DNA nanorobots developed against cancer by researchers from the Chinese Academy of Sciences and Arizona State University.

Why use nanorobots against cancer?

In recent years, nanomedicine, or nanotechnology application to health sciences, has become one of the most emerging areas of medicine. Nanomedicine aims to prevent, diagnose and treat diseases through, for example, the development of nanoparticles programmed to detect the presence of pathology or designed to transport drugs to the affected tissue.

Within the field of oncology, for some time, researchers have considered how to develop nanoparticles that would track and destroy tumour cells without attacking normal cells in the body. As in any war, “tracking and destroying the enemy” or “fighting the enemy” are comprehensive to carry out practical actions. However, it may be more beneficial to define a concrete action strategy.

In this case, the researchers proposed a simple and concrete objective to attack cancer: block the supply of nutrients and “starve” the tumour. How? Inducing blood coagulation in the tumour’s blood vessels utilising DNA-based nanoparticles that carry coagulating agents to that area. If the blood, responsible among other functions for transporting nutrients and oxygen to the cells, cannot access the tumour, it does not receive reinforcements to carry out its metabolism. In military terms, it would be something like starting a siege on the city to be conquered and preventing any arrival of reinforcements from outside.

How to use nanotechnology to besiege a tumour

To carry out a siege at the microscopic level, the researchers needed to design nanoparticles that fulfilled two main characteristics:

  1. They had to recognise the blood vessels that feed the tumour and differentiate its cells from normal cells.
  2. Second, the nanoparticles had to be able to release a coagulating agent once at their destination.
  3. Third, the DNA-based nanorobots that the researchers have developed meet both conditions.

DNA is made up of units that allow it to create diverse shapes with the ability to fold. The creation of these nanoscopic shapes is called DNA origami by researchers. And its properties can be used to design structures with therapeutic agents that unfold and release these agents when they reach their target.

In this case, the team developed a type of nanorobot made up of a rectangular sheet of DNA measuring 90 nanometers by 60 nanometers with four molecules of thrombin, a clotting enzyme, attached to its surface. This DNA sheet also had the characteristic of folding autonomously into a tube so that the thrombin molecules remained inside. 

The researchers added molecules called DNA aptamers to the DNA sheet to ensure that the nanorobots would perform their function only in tumours. These molecules recognise the protein nucleolin, produced in large quantities by the endothelial cells of tumours. Furthermore, the recognition between DNA aptamers and nucleolin is an activation switch for the nanorobots.

Thus, the mechanism is as follows: first, the researchers inject DNA nanorobots loaded with thrombin into the bloodstream of animal models for cancer; when the blood vessels that nourish the tumour arrive, the nanorobots detect the presence of nucleolin thanks to the DNA aptamers and are activated, passing from the cylindrical shape to the unfolded condition that exposes the thrombin molecules; Finally, thrombin initiates a coagulation process that ends up blocking blood flow to the tumour. 

Promising results in animal models

The nanorobot treatment showed no signs of toxicity in the treated model animals. After injection, the concentration of nanorobots in the body decreased, which meant that the nanoparticles could be degraded or eliminated by the body. The safety of the nanorobots was confirmed in Bama pigs, which show more remarkable similarity to humans than mice in anatomy and physiology.

Furthermore, to assess their efficacy against tumours in vivo, the researchers treated various animal models of cancer with DNA nanorobots. In just 24 hours after treatment, the team observed the production of thrombosis in the tumour blood vessels, and in three days, all the blood vessels of the analysed tumours had been blocked.

The coagulation of blood vessels as an antitumor treatment showed greater effectiveness in tumours with a high degree of vascularisation, as in melanoma. Three of the eight model mice for this type of cancer showed complete regression of the tumours. In these animals, treatment with nanorobots also slowed down metastasis. Furthermore, DNA-based nanorobots slowed tumour growth in other types of cancer, such as lung cancer.

The future of nanorobots in oncology

The performance of DNA-based nanorobots as a tool to fight cancer shows how advanced the field of nanomedicine is. In light of the results obtained, published in the latest issue of Nature Biotechnology, the responsible researchers are looking for clinical partners with whom they can advance the technology.

“We have developed the first fully autonomous DNA robotic system to design an exact drug and targeted cancer therapy,” says Hao Yan, a researcher at Arizona State University and one of the project leaders. “Also, this technology is a strategy that can be used in many types of cancer, since all the blood vessels that feed solid tumours are essentially the same.”

As the article’s authors point out, the promising results of DNA nanorobots could inspire the design of new cancer treatments using different modified molecules to mediate the administration of therapeutic agents. Combining different designer nanorobots carrying various agents could help eradicate solid tumours and derived metastases. And even the researchers point out that the strategy could be modified as a treatment delivery platform for other diseases.