Exploding microbubbles tear apart cancer cells like "targeted warheads"
Lately we've seen an exciting string of research projects demonstrate how ultrasound can be harnessed to fight cancer, whether that be by helping drugs cross the blood-brain barrier, heating and destroying tissue in prostate cancers, or selectively killing tumor cells while leaving healthy ones unharmed. Adding to this burgeoning potential is a new study that combines ultrasound with microbubbles, which can be blasted apart like a “targeted warhead” to destroy the majority of tumor cells in breast cancer models.
The breakthrough was made by an international research team led by biomedical engineers at Israel’s Tel Aviv University (TAU), where the scientists were experimenting with microbubbles as a way of treating cancer. These tiny bubbles are filled with gas and, when subjected to sound waves at certain frequencies, can behave like balloons that expand and contract.
“We discovered that using lower frequencies than those applied previously, microbubbles can significantly expand, until they explode violently,” says TAU’s Dr Tali Ilovitsh, who led the team. “We realized that this discovery could be used as a platform for cancer treatment and started to inject microbubbles into tumors directly."
The next round of experiments produced some exciting results. The team found that by directly injecting the microbubbles into tumors in mouse models, and then applying a low frequency ultrasound of 250 kHz to blow them up, they were able to wipe out large numbers of the cancerous cells.
"About 80 percent of tumor cells were destroyed in the explosion, which was positive on its own," says Dr. Ilovitsh. "The targeted treatment, which is safe and cost-effective, was able to destroy most of the tumor. However, it is not enough. In order to prevent the remaining cancer cells to spread, we needed to destroy all of the tumor cells. 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."
This two-pronged approach brought even more impressive results. The explosions caused pores to open up in the membranes of the remaining cells, enabling the immunotherapy gene to gain entry and prompt an immune response that consequently killed them off.
"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 explains. "The gene caused the cells to produce a substance that triggered the immune system to attack the cancer cell. In fact, our mice had tumors 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."
Another exciting and novel application for this ultrasound-microbubble combination concerns the treatment of neurodegenerative diseases like Alzheimer’s. One study published in April showed how ultrasound treatment can cause injected microbubbles to cause temporary disruptions to the blood-brain barrier to allow the penetration of drugs that treat the disease. Ilovitsh hopes to use this new approach to pursue similar objectives.
"The blood-brain barrier does not allow for medications to penetrate through, but microbubbles can temporary open the barrier, enabling the arrival of the treatment to the target area without the need for an invasive surgical intervention,” she says.
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: Tel Aviv University