ACS Appl Mater Interfaces. 2018 Mar 28;10(12):9949-9956. doi: 10.1021/acsami.7b19755. Epub 2018 Mar 15.
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.
壳稳定的气体纳米气泡因其在超声分子成像和癌症治疗的造影剂方面的潜在应用而引起了研究界的关注。然而，亚微米气体气泡（尤其是未涂层的气泡）的存在一直存在争议，部分原因是其预测的拉普拉斯超压达到几个大气压，使它们在热力学上不稳定。此外，超声与纳米粒子相互作用产生的反向散射在临床相关频率下预计不易检测到。尽管如此，最近的一些报告已经成功地研究了纳米气泡在超声成像中的存在和应用。这些观察结果背后的机制尚不清楚，但部分原因是气泡稳定壳的生物物理特性有很大影响。在这项研究中，我们研究了将嵌段共聚物表面活性剂 Pluronic 掺入纳米气泡的脂质单层中的效果。使用悬滴和上升滴原理的光学张力计研究了壳组成对膜平衡表面张力的影响。然而，这些技术被证明不足以解释在超声下观察到的纳米气泡的行为和稳定性。此外，我们试图通过 Langmuir-Blodgett 实验研究不同压缩程度下（类似于超声场中的气泡振动）膜表面张力（表面压力）的变化。这项研究的结果表明，通过掺入 Pluronic L10，纳米气泡的平衡表面张力显著降低（p < 0.0001），尤其是在 0.2 的比例下，该值降低了 28%。然而，这种表面压力的降低仅在特定的组成下观察到，并且随单层结构（结晶相或液晶堆积）而变化。这些结果表明存在优化的可能性，其中可以通过适当的脂质与 Pluronic 平衡和微结构来最大化表面压力，以适应收缩和扩张阶段。
