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首页> 外文期刊>RSC Advances >Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents
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Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents

机译：形成单分散过热全氟化碳纳米液滴作为可活化超声造影剂的新方法

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摘要

Microbubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>1012 vs. >1010 NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were sufficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells.
机译：微泡（MB）造影剂对全球临床超声（US）社区产生了积极影响。由于其在血管空间中的有限分布，阻碍了它们在分子美国成像应用中的使用。纳米级过热全氟化碳纳米液滴（NDs）的声滴汽化（ADV）展示出作为血管外造影剂的潜力，可以促进基于美国的分子治疗学应用。然而，这些试剂是亚稳态的并且难以以高收率生产。在这里，我们报告了一种新的配制技术，该技术可使用小体积微流化技术，在体温下产生稳定，窄分散的低于300 nm的十氟丁烷（DFB）或八氟丙烷（OFP）填充的磷脂涂层ND。 DFB的最终液滴浓度较高，而OFP的最终液滴浓度较低（> 10 12 vs。 10 NDs / mL）。使用可调电阻脉冲感应（TRPS）和动态光散射（DLS）量化了ND过热的稳定性。 DFB ND在人体温度（37°C）下稳定至少2小时，而不会自发蒸发。当暴露于临床系统传递的美国诊断压力下时，这些NDs可以在体外激活。 DFB ND具有足够的稳定性，可以用抗上皮细胞粘附分子（EpCAM）抗体加工成功能化的ND，以靶向EpCAM阳性细胞。

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