Research at the Karolinska Institutet, Stockholm. Using advanced genetic engineering techniques, researchers have created a “treatment vehicle” that is only activated close to the tumour mass.
There has been a breakthrough in research into biotechnological tools capable of selectively targeting cancer cells, while leaving the healthy ones intact, thanks to DNA nanorobots (as they are called in technical jargon) developed by researchers at the Karolinska Institutet in Stockholm (the same institute that manages the selection process for the Nobel Prize in Physiology or Medicine). These nanorobots act as a kind of switch that activates the cancer treatment only at the right time and in the right place. The results of this study have been published in the scientific journal Nature Nanotechnology.
They are tiny devices designed to work on a nanometre scale, or in the order of magnitude of nanometres (a nanometre is one billionth of a metre). Thanks to their very small size, nanorobots can interact directly with cells, performing multiple functions. Specifically, DNA nanorobots can transport specific molecules.
Using these biological “tools”, Karolinska researchers managed to tansport a series of molecules, known as “ligands”, inside tumours; these molecules are able to bind to specific proteins on the surface of cancer cells, known as “Tumour Necrosis Factor (TNF) receptors”. Once activated by the ligands, the TNF receptors (which form part of the so-called “death receptors”) trigger the programmed death (or apoptosis) of the cells.
Cancer research: many unsuccessful past attempts
Over the years, various international oncology groups have made several attempts at stimulating TNF receptors to destroy cancer cells using different types of ligands or monoclonal antibodies, but the research often ran into problems because death receptors are also present in many types of healthy cells (where they help maintain balance, when necessary).
To get around the problem (i.e. to avoid triggering the death of both cancer cells and healthy cells), the Swedish researchers “hid” the instructions for producing the ligands within a nanorobot made up of genetic material “folded” in a specific way and designed to start working only in slightly acidic zones (at pH 6.5), like those of breast cancer cells (whereas the pH of healthy cells is around 7.4).
In other words, the Karolinska researchers created a type of biological origami, i.e. a DNA envelope containing information for the production of ligands, but which stays closed until it reaches the cancer cells. These cells create an acidic microenvironment, and it is only under these pH conditions that the origami envelopes open and expose the fragments of genetic material that lead to the creation of ligands (which, in turn, activate the cancer cell receptors, triggering their apoptosis).
“Tests conducted using these nanorobots on laboratory animals (mice) suffering from breast cancer led to a significant reduction (around 70%) in cancer cell growth,” explained Yang Wang, lead author of the study. “We now need to investigate whether this works in more advanced cancer models that more closely resemble the real human disease. Of course, we also need to assess any possible side effects.”
The scientists will also try to “train” the nanorobots to be able to recognise other types of cancer cells in addition to breast cancer.