Abstract
The encapsulation of gas bubbles has resulted in improved stability and added a binding capacity to shells for ultrasound-guided targeted delivery. However, this has also changed the physical and acoustical properties of the final formulation. In this study, we have evaluated three clinically-used contrast agents of different compositions, namely, Levovist, Sonazoid, and SonoVue, with respect to their sonochemical and biological effects at different concentrations. The results showed that both shell elasticity and reactivity played a role in modulating both effects influencing the extent of ultrasound-induced free-radical formation. Microbubbles with elastic shells were found to be more capable of inducing delayed symptoms of cell killing, whereas the combined use of chemically reactive robust shells and high-density gases, such as perfluorocarbons, could exert a protective effect on cells. These conclusions offer new perspectives on how microbubbles interact with biological systems and might be useful in tailoring novel microbubbles in the future.
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