Ultrasound-activated microbubbles destroy cancer cells

Researchers at Stanford University have created a non-invasive technology platform for gene delivery into breast cancer cells, utilising low-frequency ultrasound (250 kHz) to detonate microscopic tumour-targeted bubbles like warheads. The technology was developed by Tel Aviv University’s Dr Tali Ilovitsh during her postdoctorate research at Stanford, and has been described in the journal Proceedings of the National Academy of Sciences (PNAS).

“Microbubbles are microscopic bubbles filled with gas, with a diameter as small as one tenth of a blood vessel,” Dr Ilovitsh explained. “At certain frequencies and pressures, sound waves cause the microbubbles to act like balloons: they expand and contract periodically. This process increases the transfer of substances from the blood vessels into the surrounding tissue.

“We discovered that using lower frequencies than those applied previously, microbubbles can significantly expand, until they explode violently. We realised that this discovery could be used as a platform for cancer treatment and started to inject microbubbles into tumours directly.”

Dr Ilovitsh and her team used tumour-targeted microbubbles that were attached to tumour cells’ membranes at the moment of the explosion, and injected them directly into tumours in a mouse model. Around 80% of tumour cells were destroyed in the explosion.

“The targeted treatment, which is safe and cost-effective, was able to destroy most of the tumour,” Dr Ilovitsh said. “However, it is not enough. In order to prevent the remaining cancer cells to spread, we needed to destroy all of the tumour cells. That is why we injected an immunotherapy gene alongside the microbubbles, which acts as a Trojan horse, and signalled the immune system to attack the cancer cell.”

On its own, the gene cannot enter into the cancer cells, but this changed when it was co-injected together with the microbubbles. Membrane pores were formed in the remaining 20% of the cancer cells that survived the initial explosion, allowing entry of the gene into the cells. This triggered an immune response that destroyed the cancer cell.

“The majority of cancer cells were destroyed by the explosion, and the remaining cells consumed the immunotherapy gene through the holes that were created in their membranes,” Dr Ilovitsh said. “The gene caused the cells to produce a substance that triggered the immune system to attack the cancer cell. In fact, our mice had tumours on both sides of their bodies. Despite the fact that we conducted the treatment only on one side, the immune system attacked the distant side as well.”

In the future, Dr Ilovitsh intends to attempt using this technology as a non-invasive treatment for brain-related diseases such as brain tumours and other neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. She noted, “The blood–brain barrier does not allow for medications to penetrate through, but microbubbles can temporarily open the barrier, enabling the arrival of the treatment to the target area without the need for an invasive surgical intervention.”

Image credit: ©stock.adobe.com/au/psdesign1

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