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Research Highlight | August 17, 2020

Study finds that nanobubbles can exit vascular system, bringing ultrasound-based therapies one step closer to reality

A new study published in Nano Letter (May 2020) presents the first evidence that nanobubbles can exit the vascular system intact. The discovery, made by a team of Toronto-based researchers led by Drs. Gang Zheng and David Goertz (Princess Margaret Cancer Centre), helps advance the implementation of ultrasound-based therapies for cancer.

“By demonstrating that nanobubbles can be actively delivered intact beyond the vasculature, this paper opens up a realm of possibilities for ultrasound-based therapy in closer proximity to cancer cells,” said first author Carly Pellow, a PhD candidate and Vanier Scholar studying under the supervision of Dr. Gang Zheng and Dr. David Goertz.

Nanobubbles are tiny bubbles that can be injected into the blood stream along with imaging agents or cancer drugs. These nanobubbles can be manipulated using ultrasound technology, allowing physicians to better visualize or treat tumours. But despite having caught the attention of researchers in recent years, clinical use of nanobubbles has remained relatively low.

One of the reasons why this occurs is because, until now, there was little understanding of how the bubbles could be delivered deeper into the tumours.

To overcome this limitation, the team developed a novel method that uses ultrasound to convert microbubbles, which are currently used as imaging and drug delivery agents, into nanobubbles in situ, promoting their extravasation deeper into tumours. This approach could provide a means by which to access and treat deep-seated tumours in a minimally invasive manner with ultrasound -- improving targeted delivery as well as treatment, and limiting off-target effects.

“This paper presents a novel methodology capable of providing acoustic and optical spatiotemporal insights,” says Pellow. “It is our hope that this method will provide many more key insights on ultrasound agents and how they interact with tumour microvasculature to improve ultrasound-based cancer treatment.”

Study

Simultaneous Intravital Optical and Acoustic Monitoring of Ultrasound-Triggered Nanobubble Generation and Extravasation

Authors

Carly Pellow, Meaghan A. O’Reilly, Kullervo Hynynen, Gang Zheng, and David E. Goertz

Funding

This article was partly funded by a Terry Fox New Frontiers Program Project Grant in Porphysome nanoparticle-enabled image-guided cancer interventions and a Terry Fox New Investigator Award to Dr. Meaghan O’Reilly for Bubble-mediated therapy for metastatic disease in the spinal cord