Enhancing Tumor Drug Distribution With Ultrasound-Triggered Nanobubbles.

ABSTRACT

Issues with limited intratumoral drug penetration and heterogeneous drug distribution continue to impede the therapeutic efficacy of nanomedicine-based delivery systems. Ultrasound (US)-enhanced drug delivery has emerged as one effective means of overcoming these challenges. Acoustic cavitation in the presence of nanoparticles has shown to increase the cellular uptake and distribution of chemotherapeutic agents in vivo. In this study, we investigated the potential of a drug-loaded echogenic nanoscale bubbles in combination with low frequency (3 MHz), high energy (2 W/cm2) US for antitumor therapy. The doxorubicin-loaded nanobubbles (Dox-NBs) stabilized with an interpenetrating polymer mesh were 171.5 ± 20.9 nm in diameter. When used in combination with therapeutic US, Dox-NBs combined with free drug showed significantly higher (*p < 0.05) intracellular uptake and therapeutic efficacy compared with free drug. When injected intravenously in vivo, Dox-NBs + therapeutic US showed significantly higher (*p < 0.05) accumulation and better distribution of Dox in tumors when compared with free drug. This strategy provides an effective and simple method to increase the local dose and distribution of otherwise systemically toxic chemotherapeutic agents for cancer therapies.