Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Mahaveer P Purohit^#¹, Brenda J Yu^#^{1

2}, Kanchan Sinha Roy^#¹, Yun Xiang^#¹, Sedona N Ewbank^{1

3}, Matine M Azadian^{1

3}, Alex R Hart^{1

4}, Gabriella P B Muwanga^{1

3}, Payton J Martinez¹, Jeffrey B Wang^{1

5}, Ali K Taoube¹, Eric Markarian¹, Nicholas Macedo¹, Audrey K Kwan¹, Diego Gomez Lopez^{1

6}, Raag D Airan^{7

8

9}

Affiliations

¹ Department of Radiology, Stanford University, Stanford, CA, USA.
² Biophysics Program, Stanford University, Stanford, CA, USA.
³ Neurosciences Program, Stanford University, Stanford, CA, USA.
⁴ Department of Chemistry, Stanford University, Stanford, CA, USA.
⁵ Department of Anesthesiology and Critical Care Medicine, John Hopkins Hospital, Baltimore, MD, USA.
⁶ Department of Medicine, Health, and Society, Vanderbilt University, Nashville, TN, USA.
⁷ Department of Radiology, Stanford University, Stanford, CA, USA. rairan@stanford.edu.
⁸ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. rairan@stanford.edu.
⁹ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. rairan@stanford.edu.

^# Contributed equally.

PMID: 40826187
DOI: 10.1038/s41565-025-01990-5

Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Mahaveer P Purohit et al. Nat Nanotechnol. 2025.

. 2025 Aug 18.

doi: 10.1038/s41565-025-01990-5. Online ahead of print.

Authors

Affiliations

¹ Department of Radiology, Stanford University, Stanford, CA, USA.
² Biophysics Program, Stanford University, Stanford, CA, USA.
³ Neurosciences Program, Stanford University, Stanford, CA, USA.
⁴ Department of Chemistry, Stanford University, Stanford, CA, USA.
⁵ Department of Anesthesiology and Critical Care Medicine, John Hopkins Hospital, Baltimore, MD, USA.
⁶ Department of Medicine, Health, and Society, Vanderbilt University, Nashville, TN, USA.
⁷ Department of Radiology, Stanford University, Stanford, CA, USA. rairan@stanford.edu.
⁸ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. rairan@stanford.edu.
⁹ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. rairan@stanford.edu.

^# Contributed equally.

PMID: 40826187
DOI: 10.1038/s41565-025-01990-5

Abstract

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.

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Conflict of interest statement

Competing interests: R.D.A. has equity or has received consulting fees from Cordance Medical, NaviFUS and Lumos Labs and grant funding from AbbVie Inc. All other authors declare no competing interests.

References

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Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Affiliations

Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources