Targeted therapies can now be more effective with the use of ultrasound technology

By Samantha Black, PhD, ScienceBoard editor in chief

November 12, 2019 -- Biomedical engineers from the University of Southern California in Los Angeles propose a new method to direct targeted drug release in the body using acoustics. The findings describing how they manipulated ultrasonic waves were published in Applied Physics Letters on November 12, 2019.

There is a significant lack of ability to track and direct cancer therapies in clinical settings. Chemotherapy is the most widely used treatment for cancer. To combat its toxic effect, researchers have developed a variety of targeted drugs and drug carriers. These targeted therapies often have limited abilities to reach the targeted tumors.

Ultrasound has been proposed as an active stimuli-responsive physical drug delivery method to enhance local drug concentration when using microbubbles, tiny pockets of air, to noninvasively trigger a local delivery. Conventional uses of ultrasound technology has not been used for this application because it lacks sensitivity.

"In conventional drug delivery, tissue is examined ex vivo under the microscope, or radioactive materials are used to trace drugs in vivo. We propose a new way to image and move the drug precisely inside the human body by combining the new plane wave imaging method with a focused ultrasound transducer," said post-doctoral researcher Xuejun Qian.

The lack of a clinically viable method to track and direct cancer drugs to tumors is a big problem for targeted therapeutics. But a new ultrasonic method proposed by biomedical engineers from Qifa Zhou's team at the University of Southern California could enable acoustic control and real-time tracking of drug release within the body. The researchers report on their manipulation of ultrasonic waves to pinpoint drug delivery in Applied Physics Letters. 2D schematic diagram of forces on microbubbles in the tube stimulated by ultrasound. Qifa Zhou.

In the current study, the research team developed a method that eliminates background noise of ultrasound to accurately track a drug delivery vehicle (i.e. microbubbles) within a phantom blood vessel. They used a combined technique utilizing ultrasonic trapping and ultrafast plane-wave imaging which provided real-time imaging of aggregation and manipulation of microbubbles at 10 mm depth.

To achieve this pumped water through a narrow silicone tube to mimic blood flow through a blood vessel. They placed the tube beneath real pig tissue and imaged across this to make the setup more realistic. Microbubbles were introduced into the phantom blood vessel. They then applied a focused ultrasound transducer to trap the microbubbles identified by their ultrafast imaging system. They were able to trap microbubbles to a specific location on the tube wall and turned up the acoustic power to burst the bubbles by balancing acoustic radiation forces.

They hope this combination of ultrasound tracking and targeting can be translated to noninvasively directing drug-containing microbubbles to blood vessels adjacent to tumor locations in the body.

"We want to try in vivo studies on rat or rabbit to see whether the proposed method can monitor and release microbubble-based drug delivery in a real body," said Qian. "We hope to further improve the imaging resolution, sensitivity, and speed within a real case, and if it works, the long-term goal would be to move towards a human study."

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