Effect of Acoustic Radiation Force on Displacement of Nanoparticles in Collagen Gels

Penetration of nanoscale therapeutic agents into the extracellular matrix (ECM) of a tumor is a limiting factor for sufficient delivery of drugs in tumors. Ultrasound in combination with microbubbles causing cavitation, is reported to improve delivery of nanoparticles (NPs) and drugs to tumors. Acoustic radiation force (ARF) could also enhance the penetration of NPs in tumor ECM. In this work, a collagen gel was used a model for tumor ECM to study the effect of ARF on the penetration of NPs as well as deformation of collagen gels applying different ultrasound (US) parameters (varying pressure and duty cycle). The collagen gel was characterized, and diffusion of water and diffusion of NPs measured. The penetration of NPs into the gel and was measured by confocal laser scanning microscopy and numerical simulations was performed to determine the ARF and to estimate penetration distance and extent of deformation. ARF had no effect on the penetration of NPs into the collagen gels for the US parameters and gel used, whereas a substantial deformation was observed. The width of the deformation on the collagen gel surface corresponded to the US beam. Comparing ARF caused by attenuation within the gel and Langevin pressure caused by reflection at the gel-water surface, ARF was the dominant mechanism for the gel deformation. The experimental and theoretical results were consistent both with respect to NP penetration and gel deformation.