Researchers Develop Ultrasound-Based Methods to Improve Cancer Drug Delivery

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Two New Ultrasound Techniques Aim to Open Doors for Cancer Therapy

Researchers at Duke University and Case Western Reserve University have published distinct ultrasound-based techniques designed to improve the delivery of cancer therapies into tumors.

Duke University: The SonoPIN Technique

Researchers at Duke University have developed a technique called SonoPIN. The method uses commercially available microscopic bubbles coated with components that bind to tumor cell walls. When ultrasound is applied, the bubbles collapse, creating temporary openings in the cell membranes.

This approach is designed to facilitate the entry of PROTACs, a class of therapies that target proteins which assist cancer cell multiplication. According to the researchers, PROTAC molecules are typically too large to enter cells without assistance.

In laboratory experiments, the technique resulted in approximately 50% death of targeted cancer cells, while 99% of non-targeted cells remained intact.

The method may also be applicable for delivering gene editing tools and other advanced treatments. The research team plans to test the technology in animal models and has filed a patent application.

Case Western Reserve University: The Nanobubble Technique

Researchers at Case Western Reserve University have developed a method to address the dense barriers formed by solid tumors. The technique involves injecting nanobubbles filled with perfluoropropane gas into tumors and then using ultrasound to activate them.

The research team injected the nanobubbles into breast cancer models. Ultrasound waves were then directed at the tumor, causing the nanobubbles to agitate. According to the researchers, this process remodeled the tumor's microenvironment, softening its structure without destroying cells.

Agata Exner, a professor of Radiology and Biomedical Engineering, stated that "this process reduces the tumor's defenses," potentially enhancing the efficacy of existing and emerging therapies.

The treatment was observed to activate immune cells present within the tumors. These activated cells began secreting danger signals and recruiting additional immune cells to the tumor site. Killer T cells targeting the cancer also sought out other untreated tumors in the models.

• The nanobubble treatment maintained tumor softness for at least five days, in contrast to untreated tumors that became stiffer.
• When lipid nanoparticles carrying RNA to enhance T cell activity were injected, the treatment dispersed effectively throughout the tumor.

Efstathios "Stathis" Karathanasis, a professor of biomedical engineering, stated that the strategy "gently remodels the tumor microenvironment and effectively collapses the tumor walls, opening the door for drugs and immune cells."

The researchers noted that the therapy may proceed quickly to clinical testing because the nanobubbles are already being commercialized for prostate cancer detection, and ultrasound is an FDA-approved, commercially available technology.

The method is cited as particularly relevant for solid tumors where ultrasound is commonly used, such as liver, prostate, and ovarian cancers.

An Investigational New Drug application for the nanobubbles is expected within 18 months, which could enable clinical trials within two years. The research received funding from the Case Comprehensive Cancer Center and the National Institutes of Health.