Ultrasound-mediated transport of nanoparticles and the influence of particle density

Abstract

A significant barrier to successful drug delivery in cancer therapy is the limited penetration of nanoscale therapeutics deep into tumors. Ultrasound mediated cavitation has been shown to promote nanoparticle transport, but achieving tumor wide distribution still represents a considerable challenge. The current study investigates the way in which nanoparticle drug-carriers may be designed to enhance penetration under ultrasound exposure. A computational model has been developed to predict the transport of a nanoparticle in an ultrasonic field in the presence of an oscillating microbubble, by a combination of primary and secondary acoustic radiation forces, acoustic streaming, and microstreaming. Experimental investigations were also performed in a tissue-mimicking phantom to study the transport of different types of particle, in the presence or absence of a microbubble ultrasound contrast agent, at ultrasound frequencies of 0.5 MHz and 1.6 MHz with peak pressures in the range of 0–2.0 MPa. Micro- and nanoparticles with contrasting density cores ranging from 1.0 g/cm3 to 19.3 g/cm3 were used for the study. Both the theoretical and experimental results showed that the denser particles exhibit significantly greater ultrasound-mediated transport than their lower density counterparts, indicating that this is a key consideration in the design of nanoscale therapeutics.