Acoustic cavitation and sonoporation involved in ultrasound-assisted gene transfection with polyethylenimine in vitro

Abstract

It has been shown that, acoustic cavitation-induced sonoporation should play an important role in the enhancement of gene/drug delivery. However, obstacles still remain to achieve controllable sonopration outcomes. In the current work, MCF-7 cells mixed with PEI: DNA complex were exposed to 1-MHz ultrasound pulses with varied acoustic peak negative pressure, total treatment time, and pulse-repetition-frequency (PRF). The IC activities were detected using a passive cavitation detection (PCD) system and quantified as inertial cavitation dose (ICD). The DNA transfection efficiency was evaluated using flow cytometry and the cell viability was examined by PI dying assessment. Then, scan electron microscopy was used to investigate the sonopration effects on the cell membrane. The results show that: (1) the ICD generated during US-exposure could be affected by US parameters; (2) the pooled data analyses demonstrated that DNA transfection efficiency initially increased linearly with the increasing ICD, then tended to saturate instead of trying to achieve a maximum value while the ICD kept going up; and (3) the measured ICD, sonopration pore size, and cell viability exhibited high correlation among each other. All the results indicated that ICD could be used as an effective tool to monitor and control the US-mediated gene/drug delivery effect.