Delivering drugs to the brain has always been a high-stakes challenge. The blood-brain barrier (BBB)—a tightly regulated shield of cells—blocks over 98% of small molecule drugs, making treatment of neurodegenerative diseases like Alzheimer’s and Parkinson’s notoriously difficult. Now, researchers at the University of Queensland have developed a custom-built device that combines ultrasound with advanced imaging to safely and precisely deliver drugs across the BBB, while simultaneously observing how individual brain cells respond in real time.
The technique hinges on a process called sonoporation. This involves injecting microbubbles into the bloodstream and then applying focused ultrasound waves. The sound waves cause the microbubbles to oscillate and exert mechanical force on the BBB, temporarily opening tiny pores that allow drugs to pass through. While sonoporation has shown promise in previous studies, its cellular effects have remained poorly understood—until now.
Led by Dr. Pranesh Padmanabhan from UQ’s School of Biomedical Sciences and the Queensland Brain Institute, the team spent five years developing a platform that could visualize and quantify cellular changes after ultrasound exposure. Using high-speed, high-resolution microscopy, they discovered that even brief ultrasound pulses—lasting just 20 seconds—could trigger cellular responses that persisted for over an hour. Some cells recovered quickly, while others showed delayed or even fatal changes, depending on the intensity and duration of the treatment.
This ability to distinguish between healthy and damaged cells is a game-changer. It allows researchers to fine-tune ultrasound protocols to maximize drug delivery while minimizing harm. For example, in cancer therapy, cell death may be desirable, but in neurodegenerative disease treatment, preserving healthy neurons is paramount. The platform enables scientists to map these outcomes at the single-cell and single-molecule level, offering unprecedented insight into the mechanics of sonoporation.
The implications extend far beyond neurology. Sonoporation-based therapies are also being explored in cardiology and oncology, where targeted drug delivery could reduce systemic side effects and improve efficacy. The UQ device could help optimize these treatments by providing real-time feedback on cellular responses, paving the way for more personalized and precise interventions.
One of the most striking aspects of the research is its emphasis on live-cell imaging. Traditional methods rely on fixed samples and fluorescent tagging, which can distort or destroy delicate cellular structures. The UQ team overcame these limitations by modifying incubation chambers and integrating their ultrasound transducer with a state-of-the-art Airyscan microscope. This setup allowed them to capture rapid cellular events—like vesicle movement and calcium signaling—with nanometer-level precision.
As Professor Jürgen Götz, director of the Clem Jones Centre for Ageing Dementia Research, noted, understanding the exact mechanism of drug entry—whether through opened tight junctions, vesicular transport, or sonoporation—is critical for translating this technology to clinical use. The next step is to validate these findings in real brain tissue and eventually in human trials.
Article from the University of Queensland: New ultrasound imaging to map drug delivery into the brain
Abstract in Journal of Controlled Release: High-resolution imaging reveals a cascade of interconnected cellular bioeffects differentiating the long-term fates of sonoporated cells