Embolization, cutting off the blood vessels that feed tissue growth, is under investigation as a minimally-invasive cancer treatment. The approach, which starves tumours of blood supply and nutrients, typically involves injecting drugs or lodging nanoscopic beads directly into blood vessels. Recently, scientists have explored another option: gas embolotherapy.
Gas embolotherapy is based on the injection of droplets – with diameters from tens to hundreds of nanometres – into feeder vessels surrounding the tumour. These droplets are then exposed to ultrasound, which transforms them into microscopic gas bubbles via acoustic droplet vaporization (ADV). The bubbles grow large enough to block feeder vessels, such as the arterioles, thereby cutting off the tumour’s blood supply.
Now, a research team from China and France has discovered that these bubbles could also be used as potential drug delivery systems (Appl. Phys. Lett. 112 233701).
“We have found that gas embolotherapy has great potential to not only starve tumours by shutting off blood flow, but also to be used as a source of targeted drug delivery,” said first co-author Yi Feng, from Xi’an Jiaotong University.
The researchers previously used ADV to starve the tumour by blocking blood flow in the arterioles. They found that the bubbles not only blocked the arterioles, but that other gas bubbles made their way into the capillaries, resulting in vessel rupture.
In this latest study, the team performed gas embolotherapy on ex vivo rat tissue, to further explore the dynamics of the bubbles inside capillaries. The tests involved bubble formation in droplets of dodecafluoropentane (DDFP) in a bovine serum, which were injected into the blood flow.
The bubbles produced in the DDFP accumulated, sometimes merging, as they lodged themselves in the capillaries. At one point, the researchers observed a local vessel invagination (inward movement of the microvessel), which they believe was caused by the interaction between the bubble and vessel and led to a capillary rupture.
These findings suggest that gas embolotherapy could provide a two-in-one approach to cancer treatment – shutting off blood flow from the arterioles and delivering drugs through the capillaries. In addition, chemotherapy drugs could be kept localized for longer periods of time because blood flow has been shut down.
“In cancer therapy research, scientists are always interested in answering two questions: how to kill the cancer effectively and how to reduce the side effects of chemotherapeutic drugs,” said corresponding author Mingxi Wan. “We have found that gas embolotherapy has the potential to successfully address both of these areas.”
The researchers are now building an imaging system to apply the ADV gas embolotherapy method in rats.