Ultrasound-targeted delivery of systemically administered therapeutic nanoparticles

Abstract

The ultrasound (US)-targeted delivery of systemically administered drug and gene-bearing nanoparticles has emerged to become a robust area of investigation with clear clinical potential. Such approaches typically entail the concurrent injection of contrast agent microbubbles (MBs) and nanoparticles, followed by the application of US to the region of interest. US-activated MBs disrupt the surrounding microvessel, permitting nanoparticle delivery with precise spatial localization. Our group has previously shown that US-targeted nanoparticle delivery can amplify collateral artery growth, that the binding of nanoparticles to MBs enhances nanoparticle delivery, that non-viral gene nanocarrier transfection is dependent on both MB diameter and US pressure, and that solid tumor growth can be controlled by the US-targeted delivery of 5 FU nanoparticles. More recent studies center on developing MRI-guided focused ultrasound (FUS) for nanoparticle delivery across the blood brain-barrier (BBB), which is the foremost impediment to drug treatment for most central nervous system diseases. Importantly, densely PEGylated nanoparticles that have been specifically designed to penetrate brain tissue (i.e., brain-penetrating nanoparticles, BPNs) are capable of crossing the BBB after it is opened with FUS and MBs, thereby supporting the use of gene- and drug-bearing BPNs in combination with MR-guided FUS in treating disorders and pathologies of the CNS.