Acoustofluidics for simultaneous nanoparticle-based drug loading and exosome encapsulation

Nanocarrier and exosome encapsulation has been found to significantly increase the efficacy of targeted drug delivery while also minimizing unwanted side effects. However, the development of exosome-encapsulated drug nanocarriers is limited by low drug loading efficiencies and/or complex, time-consuming drug loading processes. Researchers at Duke University have developed an acoustofluidic device that simultaneously performs both drug loading and exosome encapsulation. By synergistically leveraging the acoustic radiation force, acoustic microstreaming, and shear stresses in a rotating droplet, the concentration, and fusion of exosomes, drugs, and porous silica nanoparticles is achieved. The final product consists of drug-loaded silica nanocarriers that are encased within an exosomal membrane. The drug loading efficiency is significantly improved, with nearly 30% of the free drug (e.g., doxorubicin) molecules loaded into the nanocarriers. Furthermore, this acoustofluidic drug loading system circumvents the need for complex chemical modification, allowing drug loading and encapsulation to be completed within a matter of minutes. These exosome-encapsulated nanocarriers exhibit excellent efficiency in intracellular transport and are capable of significantly inhibiting tumor cell proliferation. By utilizing physical forces to rapidly generate hybrid nanocarriers, this acoustofluidic drug loading platform wields the potential to significantly impact innovation in both drug delivery research and applications.

Schematics and mechanism of acoustofluidic drug loading

a In the acoustofluidic device, a pair of slanted interdigital transducers generate surface acoustic waves and induce droplet rotation as well as vortex streaming, which lead to concentration and fusion of the porous silica nanoparticles, exosomes, and drug within the droplet. b When the acoustofluidic device is off, silica nanoparticles, exosomes, and drug (e.g., doxorubicin) are uniformly distributed within the droplet. When the acoustofluidic device is activated, these particles (i.e., silica nanoparticles, exosomes, and drugs) are concentrated in the center of the droplet. The high concentration and shear stress simultaneously induce both drug loading into the silica nanoparticles and encapsulation of the silica particles within the exosomes. c Numerical simulation showing acoustic microstreaming and induced shear stress distribution when the device is activated. The flow direction is toward the center of the droplet. d Fluorescent images of the silica nanoparticles, exosomes, and doxorubicin show different levels of concentration before and after the acoustofluidic device is activated. Scale bar: 1 mm.