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

• Published in: The Journal of the Acoustical Society of America 2001-07, Vol.110 (1), p.588-596
• Main Authors: Guzmán, H R, Nguyen, D X, Khan, S, Prausnitz, M R
• Format: Article
• Language: English
• Subjects: Cell Membrane - diagnostic imaging; Cell Membrane Permeability; Cell Survival - physiology; Drug Delivery Systems; Flow Cytometry; Fluoresceins - metabolism; Humans; Male; Muscle, Smooth, Vascular - diagnostic imaging; Prostatic Neoplasms; Transducers; Tumor Cells, Cultured - diagnostic imaging; Ultrasonics; Ultrasonography
• ISSN: 0001-4966; 1520-8524
• DOI: 10.1121/1.1376131

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.