Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.
Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.
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DOI：
10.1016/j.nano.2016.08.020
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Exner AA
中科院分区：
文献类型：
--
作者：
Perera RH;Wu H;Peiris P;Hernandez C;Burke A;Zhang H;Exner AA
设计纳米尺度但高度回声的试剂，用于血管外成像和超声介导的药物输送，仍然是一个艰巨的挑战。我们之前已经报道了由脂质-Pluronic表面活性剂壳层稳定的回声全氟丙烷气体纳米气泡的配方。在目前的工作中，我们描述了新一代这种纳米粒子的开发，它包括由表面活性剂和脂膜稳定的全氟丙烷气体和N，N-二乙基丙烯酰胺的交联网络。所得的交联型纳米泡(CL-PEGNB)直径为95.2±25.2 nm，在24 h内对回声信号的稳定性和保留率显著提高。体内超声和荧光断层扫描分析显示，与微泡相比，CL-PEGNB具有更大的肿瘤外渗和蓄积。总而言之，这些结果表明了一种新的、更稳定的纳米级超声造影剂的能力和优势，这种造影剂可用于未来的诊断扫描和分子成像工作。传统的超声造影剂太大，无法渗出血管，使它们无法有效地成像位于癌细胞表面的靶生物标记物。本工作描述了基于脂质/表面活性剂稳定的全氟碳气体的纳米级(~100 nm)超声造影剂的配方和综合表征。为了增加超声信号的稳定性和延长超声信号的寿命，通过交联型聚合物组件进一步稳定了纳米气泡。这样的试剂可以在与临床相关的超声频率上固有地成像，以前没有描述过很少的配方后修饰。
The design of nanoscale yet highly echogenic agents for imaging outside of the vasculature and for ultrasound-mediated drug delivery remains a formidable challenge. We have previously reported on formulation of echogenic perfluoropropane gas nanobubbles stabilized by a lipid-Pluronic surfactant shell. In the current work we describe the development of a new generation of these nanoparticles which consist of perfluoropropane gas stabilized by a surfactant and lipid membrane and a crosslinked network of N, N-diethylacrylamide. The resulting crosslinked nanobubbles (CL-PEG-NB) were 95.2 ± 25.2 nm in diameter and showed significant improvement in stability and retention of echogenic signal over 24 h. In vivo analysis via ultrasound and fluorescence mediated tomography showed greater tumor extravasation and accumulation with CL-PEG-NB compared to microbubbles. Together these results demonstrate the capabilities and advantages of a new, more stable, nanometer-scale ultrasound contrast agent that can be utilized in future work for diagnostic scans and molecular imaging. Traditional ultrasound contrast agents are too large to extravasate beyond the vasculature, making them ineffective for imaging of target biomarkers located on the cancer cell surface. This work describes the formulation and comprehensive characterization of nanoparticle-sized (~100 nm) ultrasound contrast agents which are based on lipid/surfactant stabilized perfluorocarbon gas. To add stability and improve longevity of ultrasound signal, the nanobubbles are further stabilized by a crosslinked polymer component. Such agents can be inherently be imaged at ultrasound frequencies that are clinically relevant with little post formulation modification have not been previously described.