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Israeli-led research team makes breakthrough in blasting cancer cells

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The international team, led by Tel Aviv University, has developed a technique that combines the use of ultrasound together with tumor-targeted microbubbles

By ILANIT CHERNICK

An Israeli-led team of researchers has found a way to destroy cancer cells using a recently developed ultrasound technique, Tel Aviv University announced this week.

The novel method, which is being hailed as a breakthrough, combines the use of ultrasound together with tumor-targeted microbubbles. Microbubbles are intravenous contrast agents used for contrast-enhanced ultrasounds.

Dr. Tali Ilovitsh of the Biomedical Engineering Department at Tel Aviv University, who led the international research team, developed this noninvasive technology platform for gene delivery into cancer cells – primarily breast cancer – while doing her postdoctoral research at the lab of Prof. Katherine Ferrara at Stanford University.

“Once the ultrasound is activated, the microbubbles explode like smart and targeted warheads, creating holes in cancer cells’ membranes, and enabling gene delivery,” explained Ilovitsh. 

The method “utilizes low frequency ultrasound to detonate microscopic tumor-targeted bubbles,” she said, adding that in vivo, which means inside a living organism, “cell destruction reached 80% of tumor cells.”

Microbubbles, she said, are microscopic bubbles filled with gas, “with a diameter as small as one tenth of a blood vessel,” highlighted that at certain frequencies and pressures, “sound waves cause the microbubbles to act like balloons: they expand and contract periodically.”

According to Ilovitsh, this process of their technique increases the transfer of substances from the blood vessels into the surrounding tissue. 

Dr. Tali Ilovitsh of the Biomedical Engineering Department at Tel Aviv University led the international research team. (Credit: Tel Aviv University)

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

Following this revelation, the team used tumor-targeted microbubbles that were attached to tumor cells’ membranes at the moment of the explosion, and injected them directly into tumors in a mouse model. 

“About 80% of tumor cells were destroyed in the explosion, which was positive on its own,” she emphasised. “The targeted treatment, which is safe and cost effective, was able to destroy most of the tumor. 

However, she made it clear that this alone was not enough to eradicate all the tumor cells. 

“In order to prevent the remaining cancer cells from spreading, we needed to destroy all of the tumor cells,” Ilovitsh said. “That is why we injected an immunotherapy gene alongside the microbubbles, which acts as a Trojan horse, and signaled the immune system to attack the cancer cell.”

The gene cannot enter into the cancer cells by itself, but when this gene, which is aimed to enhance the immune system, was co-injected together with the microbubbles membrane pores were formed in the remaining 20% of the cancer cells that had survived the initial explosion. 

“It allowed for the gene to enter into the [remaining] cells [and] this triggered an immune response that destroyed the cancer cells,” Ilovitsh stressed.

She pointed out that the majority of cancer cells were destroyed by the explosion, while the remaining cells consumed the immunotherapy gene through the holes that were created in their membranes. 

“The gene caused the cells to produce a substance that triggered the immune system to attack the cancer cells,” she said.

What was even more intriguing was that the mice the team used in their trials had tumors on both sides of their bodies and were only treated on one side. Despite this, the immune system attacked the tumors on the other side as well.

In the wake of this breakthrough, Ilovitsh said she is planning to look into using this method for potential treatment of brain diseases such as Parkinson’s and Alzheimer’s

In the future, she said that she intends to attempt using this technology as a noninvasive treatment for brain related diseases such as brain tumors and other neurodegenerative conditions. 

“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,”  Ilovitsh concluded.

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