Sonoporation at a low MI
Résumé
Purpose: The purpose of this study was to investigate the physical mechanisms of sonoporation, to understand and ameliorate ultra- sound-assisted drug and gene delivery. Sonoporation is the transient per- meabilisation of a cell membrane with help of ultrasound and/or an ultrasound contrast agent, allowing for the trans-membrane delivery and cellular uptake of macromolecules between 10 kDa and 3 MDa.
Material & Methods: We studied the behaviour of fluorescent ultra- sound contrast agent microbubbles near cancer cells at low acoustic amplitudes. After administering an ultrasound contrast agent, HeLa cells were subjected to 6.6-MHz ultrasound with a mechanical index of 0.2 and observed with a high-speed camera.
Results: Microbubbles were seen to enter cells and rapidly dissolve. The quick dissolution after entering suggests that the microbubbles lose (part of) their shell whilst entering. We have witnessed fluorescent activity inside cells up to 24 hours after sonication.
Conclusion: We have demonstrated that lipid-shelled microbubbles can be forced to enter cells at a low mechanical index. Hence, if a therapeutic load is added to the bubble, ultrasound-guided delivery could be facili- tated at diagnostic settings. However, these results may have implica- tions for the safety regulations on the use of ultrasound contrast agents for diagnostic imaging.