Scientists at Karolinska Institutet in Sweden have created a DNA robotic switch capable of targeting and destroying cancer cells.
This innovation represents a significant advancement in the development of future cancer treatments.
The nanorobots activate the cell’s ‘death receptors’ – essential in tumour shrinkage.
The major challenge has been ensuring that these nanorobots selectively target cancer cells without harming healthy cells, as death receptors are present in all cell types.
Professor Björn Högberg led the team that discovered how to create nanoscale robots made of amino acids that could trigger these receptors.
He explained that his hexagonal nanopattern of peptides became a lethal weapon. ‘If administered as a drug, it would indiscriminately kill cells in the body, which would be catastrophic. We have concealed the weapon within a nanostructure built from DNA.’
The technique, DNA origami, has been a focal point of Professor Högberg’s research for years. Combining DNA and peptides, the team created a crucial ‘kill switch’, ensuring the nanorobots exclusively target cancerous cells.
The key lies in the pH levels. While most of the human body has a neutral pH of around 7.4, tumour environments are slightly acidic. The nanorobots remain inactive at pH 7.4 but activate and kill cells at pH 6.5.
Professor Högberg added: ‘We have managed to hide the weapon so that it can only be exposed in the environment found in and around a solid tumour.’
This innovation means the nanorobots can specifically target and eliminate cancer cells.
In laboratory tests, the nanorobots demonstrated their effectiveness, shrinking breast cancer tumours in mice by up to 70% compared to those given an inactive version.
First author Yang Wang emphasised the need for further investigation. "We now need to investigate whether this works in more advanced cancer models that more closely resemble real human disease. We must also determine the method’s side effects before it can be tested on humans.’
Additionally, the team aims to make the nanorobots even more specific to target various cancer types.
The DNA-based robotic switch autonomously displays or hides cytotoxic ligand nanopatterns based on environmental pH levels.
This is achieved through DNA origami techniques, creating a dynamic system where ligands remain hidden but can be exposed in acidic environments like those around tumours.
The core technology involves precise DNA engineering to control ligand exposure. Molecular dynamics simulations confirmed that these ligands stay hidden within the DNA structure, only becoming exposed under specific conditions. Stabilised using ultraviolet cross-linking, the DNA origami structures maintain integrity in biological environments.
This switch mechanism holds substantial potential for targeted cancer therapies. It ensures that cytotoxic ligands are displayed only in acidic tumour environments, thereby minimising damage to healthy cells and improving treatment efficacy.
The study was published in Nature Nanotechnology.
Photo: The nanorobot's weapon can only be exposed in the acidic environment found in and around a solid tumour. Illustration: Boxuan Shen
