Newly Developed DNA Nanorobot Recognizes and Destructs HER2 on Breast Cancer Cells

Around 20% of breast cancers produce unusually high levels of a protein known as human epidermal growth factor receptor 2 (HER2), reports the Mayo Clinic.

When presented on the surface of cancer cells, this signaling protein helps them grow in an uncontrolled manner and is associated with a poor prognosis. Currently, scientists have created a DNA nanorobot that identifies HER2 on breast cancer cells, targeting them for destruction. The study outcomes have been published in the ACS journal Nano Letters.

Existing therapies for HER2-positive breast cancer comprise of monoclonal antibodies—for example, trastuzumab—that bind to HER2 on cells and guide it to the lysosome, which is an organelle that disintegrates biomolecules. Reducing the levels of HER2 slows down cancer cell growth and stimulates cell death. While monoclonal antibodies can result in the death of cancer cells, they have adverse side effects and are difficult and costly to develop.

As part of an earlier research, Yunfeng Lin and colleagues identified a short sequence of DNA, known as an aptamer that identifies and binds HER2, targeting it for lysosomal degradation almost the same way as monoclonal antibodies do. However, the aptamer was not very steady in serum. Hence, the scientists wanted to check if incorporating a DNA nanostructure, known as a tetrahedral framework nucleic acid (tFNA), could improve the aptamer’s biostability and anti-cancer activity.

In order to check this, the research group developed DNA nanorobots comprising of the tFNA with an attached HER2 aptamer. When administered into mice, the nanorobots stayed in the bloodstream over twice as long as the free aptamer. Then, the scientists incorporated nanorobots to three breast cancer cell lines in petri dishes, revealing that they destroyed only the HER2-positive cell line.

The inclusion of the tFNA enabled more of the aptamer to bind to HER2 than without tFNA, resulting in decreased HER2 levels on cell surfaces. The nanorobot is much easier and less costly to develop when compared to monoclonal antibodies; however, it may require more enhancement before it could be employed to treat breast cancer in the clinic, the scientists state.

The authors recognize funding from the National Natural Science Foundation of China.

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