Generating tiny bubbles inside targeted blood vessels by using ultrasound may be a non-surgical way to starve tumors of their blood supply and deliver anticancer drugs, say scientists in China and France.
The method is called “gas embolotherapy,” and it involves injecting microscopic droplets of a substance into the blood vessels that feed tumors.
When ultrasound is applied from an external device, the droplets generate bubbles that grow bigger and block the blood vessels.
In previous work, the team was also surprised to discover that some of the bubbles got into the smaller blood vessels and caused them to rupture and become leaky.
In a paper now published in the journal Applied Physics Letters, the researchers describe exploring the approach in detail to discover more about its dynamics and how it works.
“We have found,” says first study author Yi Feng, an associate professor of biomedical engineering from Xi’an Jiaotong University in China, “that gas embolotherapy has great potential to not only starve tumors by shutting off blood flow, but also,” he continues, “to be used as a source of targeted drug delivery.”
Without a blood supply, solid tumors cannot grow more than a few millimeters, and neither can they spread.
However, they overcome this problem by producing chemicals that trigger the formation of new blood vessels — a process called angiogenesis.
Furnished with a dedicated blood supply, tumors will receive the oxygen and nutrients that help them to grow and spread into neighboring tissue and also travel to other parts of the body and set up new metastases, or secondary tumors.
One approach that scientists have so far developed to stop or slow tumor growth is drugs called “angiogenesis inhibitors,” which stop the process of blood vessel formation.
Another approach that has gained a lot of attention is “embolization,” in which blood vessels are blocked by injection of drugs or direct insertion of nano-sized beads.
Gas embolotherapy, a form of embolization, uses gas bubbles to block blood vessels. Prof. Feng and his colleagues used a technique called acoustic droplet vaporization (ADV) to generate the bubbles from injected droplets of “dodecafluoropentane” that incorporated a “bovine serum albumin.”
They carried out their experiments on tissue taken from a rat’s intestinal mesentery, which is a flap that tethers the intestines to the wall of the abdomen and is rich in blood vessels.
When they applied the ultrasound, they found that the droplets formed bubbles that came together, with some of them merging to make bigger bubbles, and then blocked the tiny blood vessels, or capillaries of the tissue.
They also observed an example of “invagination,” in which a “pouch-like cavity” forms in a blood vessel and causes it to rupture. They suggest that this was the result of the bubble interacting with the blood vessel.
The team suggests that these results show that gas embolotherapy could be used to smite cancer with a “double punch.” The first could cut off the tumor’s blood supply, and the second could deliver anticancer drugs.
Also, the drug dosage could be reduced using this method because the blocking of the blood supply would keep the drug near the tumor for a longer time.
Corresponding study author Mingxi Wan, a professor of biomedical engineering at Xi’an Jiaotong University, explains that researchers in cancer therapy are always attempting to address two issues: how to kill the tumor, and how to reduce chemotherapy side effects.
“We have found that gas embolotherapy has the potential to successfully address both of these areas.”
Prof. Mingxi Wan