Tracking and Delivering Targeted Cancer Therapeutics with Microbubbles and Sound Waves

Sound Waves

A challenge for cancer therapies is how to assure the drugs are delivered to their target. Biomedical engineers at the University of Southern California in Los Angeles developed a method using ultrasound to control and track drug release.

“In conventional drug delivery, tissue is examined ex vivo under the microscope, or radioactive materials are used to trace drugs in vivo,” said Xuejun Qian, a post-doctoral researcher in the laboratory of Qifa Zhou. “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.”

In the research, Hanmin Peng, a visiting scholar from Nanjing University of Aeronautics & Astronautics, China, and the scientific team, filled a narrow silicone tube with water to mimic blood flow through a blood vessel. The tube was then inserted beneath pig tissue and imaged to simulate realistic flesh and blood. Microbubbles can be used as drug delivery vehicles. The microbubbles were introduced into the artificial blood vessels.

The authors wrote, “Chemotherapy is a widely used and effective treatment for cancer but with systemic toxicity. To limit this side effect, different types of targeted drugs and drug carriers (e.g., liposomes or nanoparticles) have been developed in the past few decades. Microbubbles or liposomes can carry drugs or genes to small blood capillaries, where drugs and genes can be noninvasively released by ultrasound. However, literature studies have suggested that only up to 1% of the injected dose is able to reach the tumor. Therefore, different methods such as increasing the local drug concentration and targeted release around the tumor have been investigated to enhance the permeability and retention.”

Recent advances have allowed scientists to focus sound waves into what has been dubbed “acoustic tweezers,” in order to manipulate particles. The research team used a focused ultrasound transducer to trap the microbubbles that were identified by an ultrafast imaging system. They were then able to predict the motion of the microbubbles and calculate the force of the acoustic radiation needed to trap and move the bubbles to specific areas in the artificial blood vessel. Once they moved the microbubbles to the desired location, they could tune the ultrasound to burst the bubbles.

They were able to track the microbubbles at depths of up to 10 millimeters within the tissue in real time. The hope is that this combination of ultrasound tracking and targeting could be developed into a method for noninvasively directing drug-containing microbubbles to blood vessels feeding tumors.

“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.”

The research was published in the journal Applied Physics Letters.

The authors noted, “Conventional techniques for targeted drug delivery and real-time microbubble tracking suffer from the imprecise localization of the extent of the microbubble aggregation region, which limits applicability in clinic use. Our combined technique utilizing ultrasonic trapping at 2.5 MHz and ultrafast plane wave imaging at 18 MHz can provide real-time imaging of aggregation and manipulation of microbubbles at 10 mm depth.”

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