Ultrasound-mediated drug delivery to prostate cancer and smooth muscle cells

High-intensity focused ultrasound at frequencies below 1 MHz holds great promise as a noninvasive drug delivery tool to transiently permeabilize cell membranes by a mechanism involving cavitation. The use of these frequencies is of interest because it is low enough to create extensive cavitation at reasonable pressures (<10 MPa). In this study: (1) The effects of acoustic parameters on delivery of molecules into cells and on cell viability were characterized, (2) The number of molecules delivered into each cell was quantified, and (3) Correlations between the acoustic spectrum generated by ultrasound and the observed bioeffects were extracted. Uptake of calcein (a 0.6 nm radius, membrane-impermeant fluorescent marker) and fluorescently tagged bovine serum albumin (BSA, a 3.5 nm radius molecule) and cell viability were measured in human smooth muscle (SMC) and DU145 prostate cancer cell suspensions. Our results show significant delivery of molecules into the cells (e.g., 10⁶ molecules/cell) accompanied by some loss of cell viability. These effects generally increased with increasing pressure, increasing exposure time, and decreasing frequency