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Nanorobots Kill Cancer in A New DNA Origami Study

S u m m a r y :
Nanorobots designed to identfy and kill cancer cells have successfully shrunk tumours. The findings are published in the journal Nature Biotechnology.

Nanorobots Seek & Destroy

Seek and destroy: such was the task of nanorobots designed to get rid of tumours. The brains behind the nanomedicine feat, scientists from Arizona State University, the National Center for Nanoscience and Technology (NCNST), and the Chinese Academy of Sciences, created them to cut off the blood supply to the cancerous cells, a technique that has reaped its fruits.

Furthermore, it is hoped to be as effective on many forms of cancer.

“We have developed the first fully autonomous, DNA robotic system for a very precise drug design and targeted cancer therapy,” says study author Hao Yan.

“Moreover, this technology is a strategy that can be used for many types of cancer, since all solid tumour-feeding blood vessels are essentially the same.”

Yan and his colleagues, thus, successfully demonstrated the world’s very first cancer-killing nanorobot system in mammals, mouse models with breast cancer, melanoma, ovarian, and lung cancer.

DNA nanorobots using blood-clotting agent thrombin to cut the blood supply of tumour cells. The latter underwent a tumour mini heart attack leading to their death. The DNA scaffold pictured above had 4 thrombin molecules attached to it, after which the sheet folded onto itself to form a tube. Photo Credits: Jason Drees, Arizona State University.

DNA-Based System

The system is based on DNA: the latter was used to create structures that could self-fold into a variety of shapes and sizes, down to widths a thousand times smaller than that of a human hair. This process of folding, known as DNA origami, has become a great tool in nanomedicine, a field of study that exploits nanotechnology to diagnose and treat diseases like cancer. Yan himself is an expert in DNA origami, and together with his colleagues, he has gone past the usual challenges and obstacles of manipulating nanorobots that can destroy tumours without harming healthy cells. The end result is a fully programmable robotic system (consisting of DNA-based nanocarriers) that can independently do its job of cutting off the blood supply of tumours by effectively triggering blood coagulation.

“These nanorobots can be programmed to transport molecular payloads and cause on-site tumor blood supply blockages, which can lead to tissue death and shrink the tumor,” says study author Baoquan Ding.

The nanorobot system rolled into a hollow tube. It attacks only cancer cells thanks to its passengers: when bound to a tumour blood vessel, it delivers its cargo into the tumour, exposing the thrombin that does the blood clotting. Picture Credits: ASU Biodesign Institute.

The DNA Origami Folds Itself Into Tube

The nanorobots were used on a mouse tumour model, a mouse with injected human cancer cells which had, then, experienced aggressive tumour growth.

Each nanorobot bears a flat, rectangular DNA origami sheet of 90 nanometers in length and 60 nm in width, which had blood-clotting enzyme thrombin adhered to its surface. Initially, 4 thrombin molecules attached themselves onto the DNA sheet; the latter then folded onto itself to form a hollow tube. When introduced into the mice, they travelled in the blood, and sought to identify and kill cancers.

Only hours following injection, the nanorobots had already surrounded the tumour in the mice; they worked rapidly and effectively. More importantly, they appeared to be safe to use, and did not propagate into the brain of the mice.

“The nanorobot proved to be safe and immunologically inert for use in normal mice and, also in Bama miniature pigs, showing no detectable changes in normal blood coagulation or cell morphology,” says lead investigator Yuliang Zhao.

“The nanorobots are decidedly safe in the normal tissues of mice and large animals,” says study author Guangjun Nie.

Nanorobots With Therapeutic Potential

The researchers are positive that their DNA nanorobots are extremely effective in getting rid of tumours.

“The thrombin delivery DNA nanorobot constitutes a major advance in the application of DNA nanotechnology for cancer therapy,” said Yan. “In a melanoma mouse model, the nanorobot not only affected the primary tumor but also prevented the formation of metastasis, showing promising therapeutic potential.”

Tumor blood supply was cut off, leading to damage of the tumour tissues within 24 hours while healthy tissues remain unaffected. Image courtesy of ASU Biodesign Institute.

Medical Applications in the Future

This technology will now be refined, bringing it closer to be used medically.

“I think we are much closer to real, practical medical applications of the technology,” says 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 vascularised metastases. 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.”

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