Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation
Stimulus-responsive drug delivery nanotechnologies promise noninvasive activation of the right drug at the right place at the right time. However, these systems often incorporate non-validated pharmaceutical excipients and other features that limit their clinical translation. Here we engineer the responsiveness of liposomes to a pulsed, low-intensity ultrasound activating stimulus by incorporating a generally regarded as safe excipient that alters the acoustic properties of the liposome core medium. We show that this approach permits loading and ultrasound-induced release of four drugs in vitro. We then leverage this performance to enable drug-mediated noninvasive neuromodulation of each of the central and the peripheral nervous system in vivo. These acoustically activatable liposomes formulated with common and validated pharmaceutical excipients and production processes provide a versatile system for stimulus-responsive site-targeted drug delivery and noninvasive neuromodulation, with high clinical translation potential.
Authors
- Kanchan Sinha Roy (ORCID: https://orcid.org/0000-0001-7726-6788)
- Alex R. Hart
- Raag D. Airan (ORCID: https://orcid.org/0000-0001-5259-5606)
- Matine Azadian (ORCID: https://orcid.org/0000-0002-8253-7113)
- Ali K. Taoube
- Diego Gómez López
- Sedona N. Ewbank (ORCID: https://orcid.org/0000-0002-6985-1431)
- Mahaveer P. Purohit (ORCID: https://orcid.org/0000-0001-6841-6545)
- Payton Martinez (ORCID: https://orcid.org/0000-0003-2634-9502)
- Eric Markarian (ORCID: https://orcid.org/0000-0002-6462-6577)
- Gabriella P. B. Muwanga (ORCID: https://orcid.org/0000-0003-2571-2808)
- Brenda Yu (ORCID: https://orcid.org/0000-0001-8304-9851)
- Jeffrey B. Wang (ORCID: https://orcid.org/0000-0002-8933-9822)
- Nicholas Macedo
- Yun Xiang (ORCID: https://orcid.org/0000-0001-8601-9324)
- Audrey K. Kwan
Institutions
- Vanderbilt University (US)
- Stanford Medicine (US)
- Johns Hopkins Hospital (US)
- Vanderbilt Health (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Nanotechnology
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1038/s41565-025-01990-5
- Citations
- 11
- Primary Topic
- Photoacoustic and Ultrasonic Imaging
- Type
- article
- Field-Weighted Citation Impact
- 7.42
Funders
- Ford Foundation
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Division of Graduate Education