Effect of Acoustic Radiation Force on the Distribution of Nanoparticles in Solid Tumors
Mercy Afadzi, Ola Finneng Myhre, Petros Tesfamichael Yemane, Astrid Bjørkøy, Sverre H. Torp, Annemieke van Wamel, Sylvie Lélu, Bjørn Angelsen, Catharina de Lange Davies
Abstract
Acoustic radiation force (ARF) might improve the distribution of nanoparticles (NPs) in tumors. To study this, tumors growing subcutaneously in mice were exposed to focused ultrasound (FUS) either 15 min or 4 h after the injection of NPs, to investigate the effect of ARF on the transport of NPs across the vessel wall and through the extracellular matrix. Quantitative analysis of confocal microscopy images from frozen tumor sections was performed to estimate the displacement of NPs from blood vessels. Using the same experimental exposure parameters, ARF was simulated and compared with the experimental data. Enhanced interstitial transport of NPs in tumor tissues was observed when FUS (10 MHz, acoustic power 234 W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , 3.3% duty cycle) was given either 15 min or 4 h after NP administration. According to acoustic simulations, the FUS generated an ARF per unit volume of 2.0 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> N/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> . The displacement of NPs was larger when FUS was applied 4 h after NP injection compared with after 15 min. This study shows that ARF might contribute to a modest improved distribution of NPs into the tumor interstitium.