Role of Surface Tension in Gas Nanobubble Stability Under Ultrasound

Shell-stabilized gas nanobubbles have recently captured the interest of the research community for their potential application as ultrasound contrast agents for molecular imaging and therapy of cancer. However, the very existence of submicron gas bubbles (especially uncoated bubbles) has been a subject of controversy in part due to their predicted Laplace overpressure reaching several atmospheres, making them supposedly thermodynamically unstable. In addition, the backscatter resulting from ultrasound interactions with nanoparticles is not predicted to be readily detectable at clinically relevant frequencies. Despite this, a number of recent reports have successfully investigated the presence and applications of nanobubbles for ultrasound imaging. The mechanism behind these observations remains unclear but is thought to be, in part, influenced heavily by the biophysical properties of the bubble stabilizing shell. In this study, we investigated the effects of incorporating the triblock copolymer surfactant, Pluronic, into the lipid monolayer of nanobubbles. The impact of shell composition on membrane equilibrium surface tension was investigated using optical tensiometry, using both pendant drop and rising drop principles. However, these techniques proved to be insufficient in explaining the observed behavior and stability of nanobubbles under ultrasound. Additionally, we sought to investigate changes in membrane surface tension (surface pressure) at different degrees of compression (analogous to the bubble oscillations in the ultrasound field) via Langmuir-Blodgett experiments. Results from this study show a significant decrease (p < 0.0001) in the nanobubble equilibrium surface tension through the incorporation of Pluronic L10, especially at a ratio of 0.2, where this value decreased by 28%. However, this reduction in surface pressure was seen only for specific compositions and varied with monolayer structure (crystalline phase or liquid-crystalline packing). These results indicate a potential for optimization wherein surface pressure can be maximized for both contraction and expansion phases with the proper lipid to Pluronic balance and microstructure.