Ultrasound-mediated disruption of cell membranes. I. Quantification of molecular uptake and cell viability

TLDR

Ultrasound-mediated drug delivery is a nonchemical, nonviral, noninvasive method that targets transport of drugs and genes into cells by disrupting cell membranes through cavitation. The study examined how varying peak negative acoustic pressures (0.6–3.0 MPa), exposure times (120–2000 ms), and pulse lengths (0.02–60 ms) with Optison contrast agent affected molecular uptake and cell viability in DU145 prostate cancer and aortic smooth muscle cell suspensions. Higher pressure and longer exposure increased calcein uptake toward equilibrium while decreasing cell viability; pulse length had no significant effect, and all measurements correlated with acoustic energy exposure, suggesting acoustic energy predicts ultrasound’s nonthermal bioeffects.

Abstract

Ultrasound-mediated drug delivery is a nonchemical, nonviral, and noninvasive method for targeted transport of drugs and genes into cells. Molecules can be delivered into cells when ultrasound disrupts the cell membrane by a mechanism believed to involve cavitation. This study examined molecular uptake and cell viability in cell suspensions (DU145 prostate cancer and aortic smooth muscle cells) exposed to varying peak negative acoustic pressures (0.6–3.0 MPa), exposure times (120–2000 ms), and pulse lengths (0.02–60 ms) in the presence of Optison (1.7% v/v) contrast agent. With increasing pressure and exposure time, molecular uptake of a marker compound, a calcein, increased and approached equilibrium with the extra cellular solution, while cell viability decreased. Varying pulse length produced no significant effect. All viability and molecular uptake measurements collected over the broad range of ultrasound conditions studied correlated with acoustic energy exposure. This suggests that acoustic energy exposure may be predictive of ultrasound’s nonthermal bioeffects.