Nonlinear microbubble behaviour for enhanced drug uptake
Résumé
The purpose of this study was to investigate the physical mechanisms of sonoporation, to understand and ameliorate ultrasound-assisted drug and gene delivery. Sonoporation is the transient permeabilisation of a cell membrane with the help of ultrasound and/or an ultra- sound contrast agent, allowing for the trans-membrane delivery and cellular uptake of macro- molecules between 10 kDa and 3 MDa.
We studied the behaviour of ultrasound contrast agent microbubble near cancer cells at low acoustic amplitudes. After administering an ultrasound contrast agent, HeLa cells were sub- jected to 6.6-MHz ultrasound with a mechanical index of 0.2 and observed using a high-speed camera.
Microbubbles were seen to enter cells and rapidly dissolve. The quick dissolution after enter- ing suggests that the microbubbles lose (part of) their shell whilst entering.
We have demonstrated that lipid-shelled microbubbles can be forced to enter cells at a low acoustic amplitude. Hence, if a therapeutic load is added to the bubble, ultrasound-guided de- livery could be facilitated at diagnostic settings. However, these results may have implications for the safety regulations on the use of ultrasound contrast agents for diagnostic imaging.
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