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Scientific Frontline: Extended "At a Glance" Summary: Ultrasound-Activated Nanobubbles in Oncology
The Core Concept: Ultrasound-activated inert gas nanobubbles are injected into solid tumors and stimulated with sound waves to mechanically break down the dense, collagen-rich barriers that protect cancer cells, thereby enabling the effective delivery of therapeutic agents.
Key Distinction/Mechanism: Unlike traditional chemical treatments or destructive ablation, this method relies on the gentle mechanical "jiggling" of perfluoropropane-filled nanobubbles via directed ultrasound. This physical agitation remodels and softens the tumor's stiff extracellular matrix without destroying the surrounding cells, uniquely allowing large therapeutic molecules—such as RNA carried in lipid nanoparticles—and endogenous immune cells to penetrate the previously inaccessible tumor core.
Origin/History: The breakthrough was published in ACS Nano by a collaborative team of biomedical engineers and radiologists at Case Western Reserve University, led by Efstathios Karathanasis and Agata Exner, and announced in February 2026. The underlying nanobubble technology is concurrently being commercialized by Visano Theranostics for diagnostic imaging in prostate cancer.
Major Frameworks/Components:
- Perfluoropropane Nanobubbles: Inert, gas-filled lipid shells injected directly into the tumor.
- Targeted Ultrasound Activation: The use of FDA-approved ultrasound waves to trigger the mechanical vibration of the nanobubbles.
- Microenvironment Remodeling: The physical breakdown of dense collagen walls that solid tumors utilize to block drug penetration.
- Endogenous Immune Activation: The secondary therapeutic effect wherein the mechanical disruption triggers tumor-infiltrating immune cells to release danger signals, recruiting killer T cells to attack both the targeted tumor and distant untreated tumors.
Branch of Science: Biomedical Engineering, Nanomedicine, Oncology, and Immunotherapy.
Future Application: This strategy is poised to enhance the efficacy of existing and emerging cancer therapies for difficult-to-treat solid tumors, including liver, prostate, and ovarian cancers. Because the nanobubbles and ultrasound technology are already developed or FDA-approved for other applications, clinical trials utilizing this combinatorial therapeutic approach are anticipated within two years.
Why It Matters: Solid tumors construct formidable physical fortresses that severely limit the delivery and success of advanced cancer drugs, particularly new immunotherapies. By disarming the cancer's physical defenses and simultaneously stimulating a systemic immune response, this non-destructive technique possesses the potential to drastically improve survival rates and optimize the performance of nearly any solid tumor therapy currently on the market.
Researchers at Case Western Reserve University have discovered a way to breach one of cancer’s most stubborn defenses: the impenetrable fortress that solid tumors build around themselves.
By injecting nanobubbles filled with inert gas into tumors and “jiggling” them with ultrasound, the team successfully broke down tumor barriers enough for treatment-bearing molecules to get inside, according to results of a new study published in ACS Nano.
“The physical barrier is limiting delivery of cancer drugs, especially for new immunotherapies,” said Efstathios "Stathis" Karathanasis, vice chair and professor of biomedical engineering, a joint department of Case School of Engineering and Case Western Reserve School of Medicine. “We developed a strategy that uses ultrasound-activated nanobubbles, which gently remodels the tumor microenvironment and effectively collapses the tumor walls, opening the door for drugs and immune cells.”
The therapy could potentially be fast-tracked to clinical testing because the nanobubbles are already being commercialized for detecting prostate cancer, and the ultrasound is approved by the U.S. Food and Drug Administration (FDA) and commercially available.
How it works
As tumors grow, they create unusually stiff, dense tissue around them—made mostly from collagen, the protein that forms scar tissue. This barrier prevents modern immune therapies, particularly RNA carried in lipid nanoparticles, from reaching immune cells inside the tumor.
In a breast cancer model, the researchers injected nanobubbles filled with an inert gas, perfluoropropane, into a tumor. Then, using ultrasound, they directed sound waves at the tumor to gently “jiggle” the bubbles, breaking down the tumor’s stiff structure without destroying cells.
The collaboration between Karathanasis’s nanotechnology and immunotherapy lab and the ultrasound and nanomedicine lab of Agata Exner, the Henry Willson Payne Professor of Radiology at the medical school and director of the CWRU Center for Imaging Research, found that the tumors became softer, more homogeneous and more penetrable by immune cells and nanoparticles.
“We drop the defenses of the cancer and give a fair chance for our therapies to actually win,” said Exner, also a professor of biomedical engineering. “We didn’t invent a new drug, but it has the potential to make any existing or emerging therapy work much better.”
Activating the body’s own defenses
Even more remarkable: The treatment activated immune cells already inside tumors without additional therapies.
“They start secreting danger signals and recruiting more immune cells to the site of the tumor,” Karathanasis said. “Not only that, the killer T cells that target that cancer will also seek out other tumors—even ones that weren’t treated.”
The nanobubble treatment made the tumors softer for at least five days, while untreated tumors grew stiffer and more difficult to treat. When the researchers later injected lipid nanoparticles containing RNA that enhanced the tumor’s T cell activity, the treatment dispersed throughout the tumor rather than remaining at the injection site.
Path to clinical trials
“Any tumor that you can biopsy can potentially have nanobubbles introduced,” Exner said. “This is especially important for solid tumors that are difficult to treat, where ultrasound is already used, like liver, prostate and ovarian cancers.”
The nanobubbles, developed in Exner’s lab, are being commercialized for detecting prostate cancer by Visano Theranostics, a company she co-founded. Exner said an Investigational New Drug application will be submitted to the FDA within the next 18 months, and the therapeutic use could piggyback on that application, potentially enabling clinical trials within two years.
Funding: The research was funded by a grant from the Case Comprehensive Cancer Center and the National Institutes of Health.
Published in journal: ACS Nano
Authors: Anubhuti Bhalotia, Diarmuid W. Hutchinson, Theresa Kosmides, Pinunta Nittayacharn, Meghna Mehta, Arya Iyer, Andrew Cheplyansky, Koki H. Takizawa, Abraham Nidhiry, Anna M. Dever, Kyle A. Cousens, Inga M. Hwang, Gopalakrishnan Ramamurthy, Agata A. Exner, and Efstathios Karathanasis
Source/Credit: Case Western Reserve University | Diana Steele
Reference Number: bmed022426_01
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