Ultrasound-induced cell lysis and sonoporation enhanced by contrast agents

The enhancement of ultrasound-induced cell destruction, lysis, and sonoporation in low cell concentration suspensions ${\text{(2×10}}^5/\mathrm{mL})$ by the presence of contrast agents (gas bubble to cell ratio=230) was demonstrated using cervical cancer cells $(\mathrm{HeLa}\text{\hspace{0.05em}S3)}$ suspensions containing micron-size denatured albumin microspheres filled with air (Albunex®) or octafluoropropane (Optison™). The suspensions were insonificated by 2-MHz continuous or tone burst ultrasound in near field. The spatial peak-pressure amplitude was 0.2 MPa. The enhancement of cell destruction due to Optison™ was shown to be much higher than that due to Albunex® for similar bubble concentration and ultrasound conditions. For tone burst exposures, significant lysis and sonoporation only occurred in the presence of a contrast agent. The majority of the bioeffects observed occured in the first 5 min of exposure. The relationship between the enhancement of bioeffects and duty cycle of tone burst ultrasound appears to indicate that both stable gas spheres of contrast agents and cavitation nuclei created by the disruption of the gas spheres play a significant role in causing the bioeffects.