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Targeted Gold Nanoparticles as an Indicator of Mechanical Damage in an Elastase Model of Aortic Aneurysm.
Annals of Biomedical Engineering ( IF 3.8 ) Pub Date : 2020-04-02 , DOI: 10.1007/s10439-020-02500-5
Brooks A Lane 1 , Xiaoying Wang 2 , Susan M Lessner 1, 3 , Naren R Vyavahare 2 , John F Eberth 1, 3
Affiliation  

Elastin is a key structural protein and its pathological degradation deterministic in aortic aneurysm (AA) outcomes. Unfortunately, using current diagnostic and clinical surveillance techniques the integrity of the elastic fiber network can only be assessed invasively. To address this, we employed fragmented elastin-targeting gold nanoparticles (EL-AuNPs) as a diagnostic tool for the evaluation of unruptured AAs. Electron dense EL-AuNPs were visualized within AAs using micro-computed tomography (micro-CT) and the corresponding Gold-to-Tissue volume ratios quantified. The Gold-to-Tissue volume ratios correlated strongly with the concentration (0, 0.5, or 10 U/mL) of infused porcine pancreatic elastase and therefore the degree of elastin damage. Hyperspectral mapping confirmed the spatial targeting of the EL-AuNPs to the sites of damaged elastin. Nonparametric Spearman’s rank correlation indicated that the micro-CT-based Gold-to-Tissue volume ratios had a strong correlation with loaded (ρ = 0.867, p-val = 0.015) and unloaded (ρ = 0.830, p-val = 0.005) vessel diameter, percent dilation (ρ = 0.976, p-val = 0.015), circumferential stress (ρ = 0.673, p-val = 0.007), loaded (ρ = − 0.673, p-val = 0.017) and unloaded (ρ = − 0.697, p-val = 0.031) wall thicknesses, circumferential stretch (ρ = − 0.7234, p-val = 0.018), and lumen area compliance (ρ = − 0.831, p-val = 0.003). Likewise, in terms of axial force and axial stress vs. stretch, the post-elastase vessels were stiffer. Collectively, these findings suggest that, when combined with CT imaging, EL-AuNPs can be used as a powerful tool in the non-destructive estimation of mechanical and geometric features of AAs.



中文翻译:

靶向金纳米颗粒作为主动脉瘤弹性蛋白酶模型中机械损伤的指标。

弹性蛋白是一种关键的结构蛋白,其病理降解决定了主动脉瘤 (AA) 结果。不幸的是,使用当前的诊断和临床监测技术,只能侵入性地评估弹性纤维网络的完整性。为了解决这个问题,我们采用了碎片化弹性蛋白靶向金纳米粒子 (EL-AuNPs) 作为评估未破裂 AA 的诊断工具。使用微型计算机断层扫描 (micro-CT) 和量化相应的金与组织体积比在 AA 内可视化电子致密 EL-AuNP。金与组织的体积比与注入的猪胰腺弹性蛋白酶的浓度(0、0.5 或 10 U/mL)密切相关,因此与弹性蛋白损伤的程度密切相关。高光谱映射证实了 EL-AuNPs 对受损弹性蛋白部位的空间靶向。ρ  = 0.867, p -val = 0.015) 和卸载 ( ρ  = 0.830, p -val = 0.005) 血管直径、扩张百分比 ( ρ  = 0.976, p -val = 0.015)、圆周应力 ( ρ  = 0.673, p -val = 0.007)、加载 ( ρ  = − 0.673, p -val = 0.017) 和卸载 ( ρ  = − 0.697, p -val = 0.031) 壁厚、圆周拉伸 ( ρ  = − 0.7234, p -val = 0.018) 和管腔面积顺应性 ( ρ  = − 0.831, p-val = 0.003)。同样,就轴向力和轴向应力与拉伸的关系而言,弹性蛋白酶后血管更硬。总的来说,这些发现表明,当与 CT 成像相结合时,EL-AuNPs 可以用作无损估计 AA 机械和几何特征的强大工具。

更新日期:2020-04-02
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