Nanoparticle Dynamics in Composite Hydrogels Exposed to Low-Frequency Focused Ultrasound

Area of Science:

• Biomedical Engineering
• Acoustic Physics
• Materials Science

Background:

• Pulsed focused ultrasound (FUS) with microbubbles enhances nanoparticle delivery in tumors.
• Understanding FUS's role without microbubbles is key to elucidating nanoparticle transport mechanisms in the tumor extracellular matrix (ECM).

Purpose of the Study:

• To evaluate the contribution of pulsed FUS alone on nanoparticle penetration and transport within a tumor ECM model.
• To investigate FUS-induced changes in nanoparticle diffusion and acoustic streaming in a simulated tumor environment.

Main Methods:

• A composite agarose hydrogel was developed to mimic tumor ECM properties (porosity, acoustic attenuation, hydraulic conductivity).
• Single-particle tracking was employed to monitor nanoparticle dynamics within the hydrogel during FUS exposure (1 MHz, 1 MPa).
• Nanoparticle diffusion coefficients and acoustic streaming were analyzed at various FUS duty cycles and compared to theoretical models.

Main Results:

• Nanoparticles exhibited anomalous diffusion in the hydrogel.
• A 20% FUS duty cycle significantly increased the nanoparticle diffusion coefficient by 23% compared to controls.
• FUS at duty cycles above 10% caused hydrogel displacement, while acoustic streaming remained negligible.

Conclusions:

• Pulsed FUS alone does not fully account for the enhanced nanoparticle penetration observed with FUS and microbubbles.
• FUS can increase nanoparticle diffusion in the tumor ECM, but its mechanical effects on the matrix must be considered.
• FUS may serve as a supplementary tool for enhancing particle diffusion in the tumor ECM, independent of microbubble effects.