Researchers have created tiny DNA nanorobots that can deliver a protein payload that cuts off the blood supply to tumors in mice.

DNA Origami

According to a new study, the research team was able to create DNA nanorobots that can travel through the bloodstream, locate tumors, and deliver a protein that induces blood clotting, thus blocking the supply of blood to these tumors and causing them to die.

The researchers began by creating a self-assembling, rectangular DNA-origami sheet. They then linked thrombin, one of the enzymes responsible for blood clotting, to this sheet. Next, they formed the sheet into a tube and pinned it using DNA fasteners to join the edges; this resulted in a tubular nanorobot carrying a payload of thrombin within.

Perhaps the most impressive was how they designed the DNA fasteners, which were made to disconnect when encountering nucleolin, a protein unique to the surface of tumor blood vessel cells. Once this happens, the tube pops open and delivers the blood-clotting payload to the blood vessel of the tumor.







Cutting off the blood supply

Finally, the researchers injected these nanorobots into mice with human breast cancer tumors. As hoped, when the nanorobots encountered tumor blood vessel cells, they deployed their payloads and caused extensive blood clots within a 48-hour period. Even better, they caused no blood clotting elsewhere in the mice, so they were only reacting to tumor blood vessel cells as planned.

The blood clots caused necrosis in the tumors as they were starved of blood and the nutrients it carries. The result was that the treated mice had a higher survival rate than the control mice. They also found similarly increased survival in a mouse model of melanoma and in mice with xenografts of human ovarian cancer cells.

They also tested the therapy on micro pigs to see if any clotting was caused; none was observed, which is good news for potential translation of the technique to humans.

Conclusion







More studies are needed to ensure that there are no unwanted side effects, such as clotting elsewhere or immune responses created by this technique. However, taking this therapy from mice to humans will be a hugely challenging step, as it is not yet clear that targeting nucleolin to deliver thrombin will be effective in humans.

That said, the study is certainly a breakthrough because this technique serves as a platform that could potentially be used to deliver other useful proteins to target cells. It is not hard, for example, to see their potential for delivering an apoptosis-inducing protein to senescent cells if a suitable and unique surface marker can be identified on those cells.

Literature

[1] Zhang, Q., Jiang, Q., Li, N., Dai, L., Liu, Q., Song, L., … & Du, Y. (2014). DNA origami as an in vivo drug delivery vehicle for cancer therapy. Acs Nano, 8(7), 6633-6643.