In this paper, we report ultrasonically active nanoscale
contrast agents that behave as thermometric sensors through phase change in their stabilizing
phospholipid monolayer.
Phospholipid-stabilized, hydrophobic mesoporous
silica nanoparticles (P@hMSNs) are known to interact with high-intensity focused ultrasound (HIFU) to promote cavitation at their surfaces, which can be used for both imaging and
therapy. We show that the lateral
lipid phase behavior of the
phosphocholine lipid dictates the acoustic contrast of the P@hMSNs. When the
lipids are in the gel phase below their melting temperature, the P@hMSNs generate detectable
microbubbles when exposed to HIFU. However, if the
lipids exhibit a liquid expanded phase, the P@hMSNs cease to generate bubbles in response to HIFU insonation. We verify that the heating and subsequent transition of
lipid coating the
hMSN are associated with the loss of acoustic response by doping
laurdan dye into the
lipid monolayer and imaging
lipid phase through red shifts in emission spectra. Similarly, cessation of cavitation was also induced by adding a fluidizing
surfactant such as Triton X, which could be reversed upon washing away the excess
surfactant. Finally, by controlling for the partial fluidization caused by the adsorption of
protein, P@hMSNs may be used as thermometric sensors of the bulk fluid temperature. These findings not only impact the utilization of nanoscale agents as stimulus-responsive ultrasound
contrast agents but also have broader implications for how cavitation may be initiated at surfaces coated by a
surfactant.