使用相变全氟化碳纳米液滴的气泡膨胀作为增强型超声成像和治疗的策略。,Langmuir

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使用相变全氟化碳纳米液滴的气泡膨胀作为增强型超声成像和治疗的策略。
Langmuir ( IF 3.7 ) Pub Date : 2020-02-23 , DOI: 10.1021/acs.langmuir.9b03647
Carlos J Brambila _{1,

2} , Jacques Lux _{1,

2,

3} , Robert F Mattrey _{1,

2,

4} , Dustin Boyd ₁ , Mark A Borden ₅ , Caroline de Gracia Lux _{1,

2}

Affiliation

相变全氟化碳微滴是在二十多年前引入的，以封闭体内下游血管。近来，人们对全氟化碳纳米液滴的兴趣日益浓厚，以实现血管外靶向，通过将全氟化碳液滴转化为微气泡来挽救微弱的超声波信号，并改善基于超声的疗法。尽管有极大的科学兴趣和进步，但由于功效和安全性问题，相变全氟化碳试剂的应用尚未达到临床测试，其中一些仍无法解释。在这里，我们报告血液中全氟化碳液滴和微气泡的共存是观察到的副作用的主要因素，当液滴自发或有意蒸发而形成微气泡时，这是不可避免的。我们发展该理论来解释为什么液滴和微气泡共存会导致全氟化碳从液滴转移到相邻微气泡而引起的微气泡膨胀。我们还提供了实验数据，显示了多达6个数量级的微气泡体积膨胀，这在存在全氟化碳纳米液滴的情况下阻塞了200 µm的管道。更重要的是，我们证明微气泡的膨胀速率和最终尺寸可以通过操纵配方参数来控制，以针对潜在的治疗应用定制药物的设计，同时最大程度地降低风险与收益的比。我们还提供了实验数据，显示了多达6个数量级的微气泡体积膨胀，这在存在全氟化碳纳米液滴的情况下阻塞了200 µm的管道。更重要的是，我们证明微气泡的膨胀速率和最终尺寸可以通过操纵配方参数来控制，以针对潜在的治疗应用定制药物的设计，同时最大程度地降低风险与收益的比率。我们还提供了实验数据，显示了多达6个数量级的微气泡体积膨胀，这在存在全氟化碳纳米液滴的情况下阻塞了200 µm的管道。更重要的是，我们证明微气泡的膨胀速率和最终尺寸可以通过操纵配方参数来控制，以针对潜在的治疗应用定制药物的设计，同时最大程度地降低风险与收益的比率。

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Bubble Inflation Using Phase-Change Perfluorocarbon Nanodroplets as a Strategy for Enhanced Ultrasound Imaging and Therapy.

Phase-change perfluorocarbon microdroplets were introduced over two decades ago to occlude downstream vessels in vivo. Interest in perfluorocarbon nanodroplets has recently increased to enable extravascular targeting, rescue the weak ultrasound signal of perfluorocarbon droplets by converting them to microbubbles, and to improve ultrasound-based therapy. Despite great scientific interest and advances, applications of phase-change perfluorocarbon agents have not reached clinical testing because of efficacy and safety concerns, some of which remain unexplained. Here, we report that the coexistence of perfluorocarbon droplets and microbubbles in blood, which is inevitable when droplets spontaneously or intentionally vaporize to form microbubbles, is a major contributor to the observed side effects. We develop the theory to explain why the coexistence of droplets and microbubbles results in microbubble inflation induced by perfluorocarbon transfer from droplets to adjacent microbubbles. We also present the experimental data showing up to 6 orders of magnitude microbubble volume expansion, which occludes a 200-µm tubing in the presence of perfluorocarbon nanodroplets. More important, we demonstrate that the rate of microbubble inflation and ultimate size can be controlled by manipulating formulation parameters to tailor the agent's design for the potential theranostic application while minimizing the risk to benefit ratio.

更新日期：2020-03-10

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