Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities.
Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities.
复制标题
DOI：
10.1021/acsami.6b12932
复制
发表时间：
2017-02-01
影响因子：
9.5
通讯作者：
Reimhult E
中科院分区：
文献类型：
--
作者：
Lassenberger A;Scheberl A;Stadlbauer A;Stiglbauer A;Helbich T;Reimhult E
超顺磁性纳米氧化铁(SPION)作为磁共振成像(MRI)的阴性对比剂首次应用于生物医学领域，引起了人们的极大兴趣。然而，具有葡聚糖包裹的多分散氧化铁纳米颗粒簇的第一代MRI造影剂仅限于肝脏和脾的成像；这与其在生物介质中的胶体稳定性差以及无法逃避网状内皮系统的清除有关。我们研究了新一代单独接枝聚乙二醇核-壳SPION在弛豫度和细胞摄取方面的不同性能，并将它们与基准氧化铁造影剂进行了比较。这些聚乙二醇接枝的Spion由于其非凡的胶体稳定性，即使在9.4T磁场下也能在水悬浮液中测量松弛系数，而不会聚集。这允许确定弛豫度的尺寸依赖标度，对于相同的核壳结构，这被证明遵循D2依赖关系。这里介绍的核心直径为∼15 nm的核壳SPION产生了比以前临床使用的造影剂以及前几代单独稳定的SPION更高的R2弛豫度。胶体稳定性扩展到控制逃避巨噬细胞清除和被蛋白质配体功能化的Spion刺激摄取，这是靶向MRI的关键要求。
Superparamagnetic iron oxide nanoparticles (SPION) have received immense interest for biomedical applications, with the first clinical application as negative contrast agent in magnetic resonance imaging (MRI). However, the first generation MRI contrast agents with dextran-enwrapped, polydisperse iron oxide nanoparticle clusters are limited to imaging of the liver and spleen; this is related to their poor colloidal stability in biological media and inability to evade clearance by the reticuloendothelial system. We investigate the qualitatively different performance of a new generation of individually PEG-grafted core–shell SPION in terms of relaxivity and cell uptake and compare them to benchmark iron oxide contrast agents. These PEG-grafted SPION uniquely enable relaxivity measurements in aqueous suspension without aggregation even at 9.4 T magnetic fields due to their extraordinary colloidal stability. This allows for determination of the size-dependent scaling of relaxivity, which is shown to follow a d2 dependence for identical core–shell structures. The here introduced core–shell SPION with ∼15 nm core diameter yield a higher R2 relaxivity than previous clinically used contrast agents as well as previous generations of individually stabilized SPION. The colloidal stability extends to control over evasion of macrophage clearance and stimulated uptake by SPION functionalized with protein ligands, which is a key requirement for targeted MRI.