DNA nanobots target HER2-positive breast cancer cells

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According to the Mayo Clinic, about 20% of breast cancers produce abnormally high levels of a protein called epidermal growth factor receptor 2 (HER2). When it is displayed on the surface of cancer cells, this signaling protein helps them proliferate uncontrollably and is linked to a poor prognosis. Researchers have developed a DNA nanorobot that recognizes HER2 on breast cancer cells, targeting them for destruction. They report their results in the ACS journal Nano Letters.

Current treatments for HER2-positive breast cancer include monoclonal antibodies, such as trastuzumab, which bind to HER2 on cells and direct it to the lysosome, an organelle degrading biomolecule. Reducing HER2 levels slows the proliferation of cancer cells and triggers cell death. Although monoclonal antibodies can kill cancer cells, they have serious side effects and are difficult and expensive to produce.

In a previous study, Yunfeng Lin and colleagues identified a short DNA sequence, aptamer, that recognizes and binds HER2, targeting it for lysosomal degradation in the same way as monoclonal antibodies. But the aptamer was not very stable in the serum. The researchers therefore wanted to know if the addition of a nanostructure of DNA, called tetrahedral frame nucleic acid (cDNA), could increase the biostability and anticancer activity of the patient. aptamer.

To find out, the team designed DNA nanorobots consisting of a tFNA associated with an aptamer HER2. When they were injected into mice, the nanobots persisted in the blood more than twice as long as the free aptamer. Next, the researchers added nanobots to three breast cancer cell lines in petri dishes, showing that they had killed only the HER2-positive cell line. The addition of tRNA allowed more aptamers to bind to HER2 than in the absence of tRNA, resulting in a reduction of HER2 levels at the surface cells. Although the nanorobot is much easier and less expensive to manufacture than monoclonal antibodies, the researchers said improvements needed to be made before they could be used to treat breast cancer in the clinic.