Design and testing of acoustically-active therapeutic nanocapsule delivery vehicles for ultrasound-targeted chemotherapy

We propose that by utilizing acoustically-active delivery vehicles (AADVs), which combine the acoustic activity of an ultrasound contrast agent (UCA) with the high payload and extravasation ability of nanoparticles, we can overcome limitations of current chemotherapy delivery methodologies. AADV were formed by conjugating nanocapsules to the shell of biotinylated UCAs. Ultrasound parameters were optimized with a 2.25 MHz focused transducer using a flow phantom to achieve both acoustic radiation force and microbubble destruction. R3230 cells cultured on a cover slip were exposed to the AADV and sonicated with the focused transducer. Fluorescence microscopy verified binding of nanocapsules to ultrasound contrast agents to form AADVs, and increased delivery of nanocapsules to cells within the focus of the transducer (relative to nanocapsule delivery without ultrasound). An order-of magnitude increase in particles were delivered to cells exposed to ultrasound compared to unexposed cells.