Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria.
Int J Nanomedicine. 2011;6:1279-90. doi: 10.2147/IJN.S18739. Epub 2011 Jun 21.
Atherosclerosis is a leading cause of mortality in the Western world, and plaque diagnosis is still a challenge in cardiovascular medicine. The main focus of this study was to make atherosclerotic plaques visible using targeted nanoparticles for improved imaging. Today various biomarkers are known to be involved in the pathophysiologic scenario of atherosclerotic plaques. One promising new candidate is the globular domain of the adipocytokine adiponectin (gAd), which was used as a targeting sequence in this study.
gAd was coupled to two different types of nanoparticles, namely protamine-oligonucleotide nanoparticles, known as proticles, and sterically stabilized liposomes. Both gAd-targeted nanoparticles were investigated for their potency to characterize critical scenarios within early and advanced atherosclerotic plaque lesions using an atherosclerotic mouse model. Aortic tissue from wild type and apolipoprotein E-deficient mice, both fed a high-fat diet, were stained with either fluorescent-labeled gAd or gAd-coupled nanoparticles. Ex vivo imaging was performed using confocal laser scanning microscopy.
gAd-targeted sterically stabilized liposomes generated a strong signal by accumulating at the surface of atherosclerotic plaques, while gAd-targeted proticles became internalized and showed more spotted plaque staining.
Our results offer a promising perspective for enhanced in vivo imaging using gAd-targeted nanoparticles. By means of nanoparticles, a higher payload of signal emitting molecules could be transported to atherosclerotic plaques. Additionally, the opportunity is opened up to visualize different regions in the plaque scenario, depending on the nature of the nanoparticle used.
动脉粥样硬化是西方世界导致死亡的主要原因，斑块的诊断仍然是心血管医学的一个挑战。本研究的主要重点是使用靶向纳米颗粒使动脉粥样硬化斑块可见，以进行改善成像。如今，已知各种生物标志物参与动脉粥样硬化斑块的病理生理情况。一种有前途的新候选物是脂联素（adiponectin）的球状结构域（gAd），它在本研究中被用作靶向序列。
gAd 与两种不同类型的纳米颗粒偶联，即精氨酸-寡核苷酸纳米颗粒，称为 proticles，和立体稳定脂质体。使用动脉粥样硬化小鼠模型，研究了 gAd 靶向的两种纳米颗粒在表征早期和晚期动脉粥样硬化斑块病变的关键情况方面的效力。从高脂饮食喂养的野生型和载脂蛋白 E 缺陷型小鼠的主动脉组织中，用荧光标记的 gAd 或 gAd 偶联的纳米颗粒进行染色。使用共聚焦激光扫描显微镜进行离体成像。
gAd 靶向的立体稳定脂质体通过在动脉粥样硬化斑块表面积聚产生强烈的信号，而 gAd 靶向的 proticles 则被内化，并显示出更多的点状斑块染色。
我们的研究结果为使用 gAd 靶向纳米颗粒进行增强的体内成像提供了有前景的视角。通过纳米颗粒，可以向动脉粥样硬化斑块输送更高载量的信号发射分子。此外，还可以根据纳米颗粒的性质，打开可视化斑块情况中不同区域的机会。
