Drug delivery technologies that respond to ultrasound have been explored for years, but many rely on perfluorocarbon nanocarriers or vaporization mechanisms that require high-intensity ultrasound. These techniques have raised concerns over tissue damage, and carriers often suffer from poor stability, limited drug loading, or inconsistent activation, making them difficult to translate into clinical use.
The new liposomes work differently. Acting as miniature sensors embedded within their architecture, they detect ultrasound signals and reliably convert them into therapeutic action. This design makes it possible to release drugs at precise sites in the body, such as specific regions of the brain, while staying within safe ultrasound exposure limits.
How They Were Designed
The researchers engineered the AALs by replacing conventional perfluorocarbons with aqueous droplets of FDA-approved excipients. They also incorporated sucrose to enhance ultrasound sensitivity while maintaining stability during storage.
The liposomes were produced through scalable methods that achieved high drug-loading efficiencies for various compounds, including for chemotherapeutics and local anesthetics. Electron microscopy confirmed their spherical structure and nanoscale size, while stability tests showed they remained intact for months under refrigeration.
To evaluate their responsiveness, the team exposed the liposomes to low-intensity pulsed ultrasound (250 kHz), which was well within clinical safety thresholds. They were then monitored for drug release and physical changes within the liposome core, measuring their ability to detect and respond to ultrasound.
Results
The sucrose-enhanced AALs proved highly responsive to ultrasound. When stimulated, they released a substantial amount of the drug, with the response driven by mechanical rather than thermal effects. This reduces the risk of tissue heating, a key safety concern with earlier systems.
Microscopy revealed that ultrasound caused mechanical stress within the aqueous core, which caused a controlled leakage of the drugs. This effectively turned the liposomes into acoustic sensors that translated sound waves into drug release.
In vivo studies further confirmed their potential, showing that AALs could uncage drugs in targeted brain regions, such as in the medial prefrontal and retrosplenial cortices, without detectable tissue injury.
The response was consistent, reproducible, and dose-controllable across the studies. The drug delivery system also proved to be versatile, accommodating multiple drug types while maintaining stability over time.
Download your PDF now!
A Dual Role: Sensor And Actuator
The study highlights the dual role of these liposomes: they act as nanoscale sensors by detecting ultrasound signals and as actuators by releasing drugs in response. This combination enables precise site-specific therapy and neuromodulation in a noninvasive manner.
The technology is designed with clinical translation in mind. It uses only FDA-approved excipients and operates safely within established ultrasound limits. Compared with earlier vaporization or sonodynamic-based systems, it offers higher safety, stability, and specificity.
Conclusion
The work could be a significant advance in ultrasound-responsive nanomedicine. By engineering liposomes that function both as sensors and actuators, the researchers have created a platform capable of delivering drugs and modulating neural activity with unprecedented precision.
With further development, this approach could enable targeted therapies for neurological disorders, localized cancer treatments, and site-specific drug delivery to otherwise inaccessible tissues without invasive procedures.
The combination of safety, stability, and responsiveness positions AALs as a promising candidate for clinical trials and future adoption in sensor-enabled medicine.
Journal Reference
Purohit M.P., et al. (2025). Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation. Nature Nanotechnology. DOI: 10.1038/s41565-025-01990-5, https://www.nature.com/articles/s41565-025-01990-5