Nanorobot Kills Cancer Cells in Mice with Hidden Weapon

Researchers at Karolinska Institutet in Sweden have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is only exposed in the tumor microenvironment, sparing healthy cells. The study is published in the journal Natural nanotechnology.

The research group at Karolinska Institutet has already developed structures that can organize cell death receptors on the surface of cells, which leads to cell death. These structures feature six peptides (chains of amino acids) assembled in a hexagonal pattern.

“This hexagonal nanopattern of peptides becomes a lethal weapon,” says Professor Björn Högberg from the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, who led the study.

“If you were to administer it as a drug, it would start indiscriminately killing cells in the body, which would not be a good thing. To get around this problem, we hid the weapon in a nanostructure built from DNA.”

Creating a “kill switch”

The art of building nanoscale structures using DNA as a building material is called DNA origami, and Högberg's research team has been working on it for many years. They have now used this technique to create a “circuit breaker” that activates under the right conditions.

“We managed to hide the weapon in such a way that it could only be exposed in the environment in and around a solid tumor,” he explains. “This means we have created a type of nanorobot that can specifically target and kill cancer cells.”

The key lies in the low pH, or acidic microenvironment that typically surrounds cancer cells, which activates the nanorobot's weapon. During cell analyzes in test tubes, the researchers were able to show that the peptide weapon is hidden inside the nanostructure at a normal pH of 7.4, but has a drastic cell killing effect when the pH drops to 6.5.

Reduced tumor growth

They then tested injecting the nanorobot into mice with breast cancer tumors. This resulted in a 70 percent reduction in tumor growth compared to mice given an inactive version of the nanorobot.

“We now need to check whether this works in more advanced cancer models that more closely resemble the real human disease,” says Yang Wang, first author of the study and a researcher at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. “We also need to find out what the side effects of the method are before we can test it on humans.”

The researchers also plan to study whether it is possible to make the nanorobot more targeted by placing proteins or peptides on its surface that bind specifically to certain types of cancer.