In what can be termed a promising avenue in cancer treatment, researchers have developed nanobots that have showcased their abilities to kill cancer cells in mice.

Previously, researchers at Karolinska Institutet developed structures that organize death receptors on the surface of cells, inducing cell death. These structures are composed of six peptides (amino acid chains) arranged in a hexagonal pattern.

Death receptors are like switches on cell surfaces that, when turned on by specific signals like tumor necrosis factor (TNF), start a process leading to cell self-destruction, known as apoptosis. They help control cell survival and death in living things.

The hexagonal nanopattern of peptides acts as a lethal weapon. Administering it as a drug would indiscriminately kill cells throughout the body, posing a significant risk. The team claims that to solve this problem, the weapon has to be hidden inside a DNA nanostructure.

DNA origami ‘kill switch’

The research team has been practicing DNA origami, the technique of creating nanoscale structures out of DNA. The process lets the team design very small shapes with high accuracy.

According to researchers, it allows them to place DNA pieces exactly where we want them and attach proteins to create precise patterns and structures at the molecular level. They have since applied this technology to develop a “kill switch” that, when triggered, acts as intended.

“We have managed to hide the weapon in such a way that it can only be exposed in the environment found in and around a solid tumor. This means that we have created a type of nanorobot that can specifically target and kill cancer cells,” said Björn Högberg, a professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, in a statement.

The nanorobot’s weapon is activated by the acidic microenvironment, characterized by a low pH, which typically surrounds cancer cells.

In test tube cell analyses, researchers demonstrated that the peptide weapon remains concealed within the nanostructure at a normal pH of 7.4. However, when the pH drops to 6.5, the weapon becomes exposed and exhibits a significant cell-killing effect.

Targeted cancer treatment

The nanorobot was tested for its efficacy by being introduced into animals with tumors related to breast cancer. Compared to mice that received an inactive version of the nanorobot, this led to a 70 percent decrease in the growth of tumors.

“We now need to investigate whether this works in more advanced cancer models that more closely resemble the real human disease,” said Yang Wang, a researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.

The team now needs to determine the method’s potential side effects before it can be tested on humans. According to researchers, potential side effects include the risk of killing healthy cells outside of tumors if the conditions are met.

“These results are an early proof of concept and are in no way a real treatment today. Our plan to investigate this includes moving to more realistic animal models that incorporate, for example, mice with humanized death receptors,” Högberg told Interesting Engineering.

In addition, the researchers plan to explore the possibility of enhancing the nanorobot’s targeting capabilities by attaching proteins or peptides to its surface that bind specifically to certain types of cancer.

The details of the team’s research were published in the journal Nature Nanotechnology.