Sound, shells, and sonoporation
Résumé
Ultrasound contrast agents consist of encapsulated bubbles in the micrometer size range. At low acoustic amplitudes these microbubbles pulsate linearly, at high amplitudes they demonstrate highly nonlinear, destructive behavior. Cellular drug uptake and lysis are increased under ultrasound insonification, and even more when a contrast agent is present, owing to the formation of transient porosities in the cell membrane (sonoporation). An overview is given of the physical mechanisms of microbubble behaviour. Microbubble oscillation and translation can be modeled using large encapsulated bubble theory. Contrast microbubbles have been observed to coalesce, fragment, crack, buckle, and jet. The number of fragments into which an insonified bubble breaks up has been related to the dominant spherical harmonic oscillation mode and to the energy absorbed by the bubble. Fragmentation thresholds computed for lipid-encapsulated microbubbles lie far below Blake's cavitation threshold. There are two hypotheses for explaining the sonoporation phenomenon, the first being bubble oscillations near a cell membrane, the second being bubble jetting through the cell membrane. Based on modeling, photography, and cellular uptake measurements, it is concluded that bubble jetting behavior is less likely to be the dominant sonoporation mechanism.