Ultrasound-activated drug release with extracellular vesicles.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuroscience

Background:

• Precise drug delivery to the nervous system remains a significant challenge in both research and clinical settings.
• Extracellular vesicles (EVs) are natural, biocompatible nanocarriers with potential for therapeutic applications.
• Developing controlled and noninvasive drug release mechanisms is crucial for advancing neurological therapies.

Purpose of the Study:

• To engineer focused ultrasound-responsive extracellular vesicles (EVs) for targeted drug delivery.
• To investigate the controlled release capabilities of these engineered EVs upon ultrasound stimulation.
• To evaluate the efficacy and safety of the EV-based drug delivery system *in vitro* and *in vivo*.

Main Methods:

• Extracellular vesicles (EVs) were loaded with therapeutic agents and a lipid-gas phase transition material (Perfluoropentane, PFP) using low-temperature sonication.
• The ultrasound responsiveness and drug release kinetics of the engineered EVs were characterized.
• The system's efficacy was tested in primary cultured neurons using lidocaine to suppress calcium activity.
• *In vivo* studies were conducted in rats to assess pain modulation.

Main Results:

• Engineered EVs, sized 100-200 nm, demonstrated efficient, on-demand drug release triggered by focused ultrasound.
• EVs loaded with lidocaine successfully reduced calcium activity in cultured neurons with minimal cytotoxicity.
• The system effectively modulated pain sensitivity in rats, demonstrating *in vivo* applicability.
• The platform exhibited safe, ultrasound-activated drug delivery with high spatiotemporal control.

Conclusions:

• Focused ultrasound-responsive EVs provide a promising platform for targeted and controlled drug delivery to the nervous system.
• This technology offers a safe and effective method for on-demand therapeutic agent release, with potential for treating neurological disorders and pain.
• The developed EVs-drugs system holds significant potential for advancing both basic neuroscience research and clinical therapeutic strategies.