Enhanced MRI relaxivity of Gd(3+) -based contrast agents geometrically confined within porous nanoconstructs.
Enhanced MRI relaxivity of Gd(3+) -based contrast agents geometrically confined within porous nanoconstructs.
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DOI：
10.1002/cmmi.1480
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发表时间：
2012-11
影响因子：
--
通讯作者：
Decuzzi, Paolo
中科院分区：
文献类型：
--
作者：
Sethi, Richa;Ananta, Jeyarama S.;Karmonik, Christof;Zhong, Meng;Fung, Steve H.;Liu, Xuewu;Li, King;Ferrari, Mauro;Wilson, Lon J.;Decuzzi, Paolo
目前批准用于临床MRI用途的钆螯合物提供的弛豫率远低于其理论极限，并且它们也缺乏组织特异性。最近，基于Gd 3+的造影剂（CA）的多孔结构内的几何限制已被提出作为一种新的，替代的策略，以提高弛豫没有化学修饰的CA。在这里，我们已经表征并优化了通过将[Gd（DTPA）（H2O）]2−（Magnevist®）负载到可注射的中孔硅颗粒的孔中获得的MRI纳米结构的性能。研究了具有三种不同孔径的纳米结构，并且在60 MHz下，它们对于5 - 10 nm孔表现出约24 mM− 1 s −1的纵向弛豫率，对于30 - 40 nm孔表现出约10 mM− 1 s −1的纵向弛豫率。对于较大的孔径，没有观察到弛豫率的增强。使用外层化合物[GdTTHA]−3和数学模型，证明弛豫率的增强是由于随着孔径的减小，旋转相关时间（CA吸附在孔壁上）和扩散相关时间（水分子的流动性降低）的增加。还观察到，在硅颗粒的外表面上的广泛的CA吸附否定了由纳米级限制提供的优点。在与HeLa细胞一起孵育后，纳米构建体在不同的颗粒/细胞比率下孵育后长达3天没有表现出显著的细胞毒性。此外，在PBS中连续搅拌24小时后，纳米结构显示出完全降解。这些数据支持并证实了以下假设：Gd 3+螯合物化合物进入多孔结构的几何限制为MRI纳米结构提供了增强的弛豫率（[Gd（DTPA）（H2O）]2−高达6倍，[GdTTHA]−3高达4倍），并可能改善稳定性，降低毒性和组织特异性。
Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~ 24 mM−1s−1 for 5 – 10 nm pores and ~ 10 mM−1s−1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer-sphere compound, [GdTTHA]−3, and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24h of continuous agitation in PBS. These data support and confirm the hypothesis that the geometrical confinement of Gd3+-chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H2O)]2−, and 4 times for [GdTTHA]−3) and, potentially, improved stability, reduced toxicity and tissue specificity.
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影响因子：
15
作者：
Moriggi, Loick;Cannizzo, Caroline;Helm, Lothar
通讯作者：
Helm, Lothar
影响因子：
4
作者：
Livramento, Joao Bruno;Helm, Lothar;Toth, Eva
通讯作者：
Toth, Eva
影响因子：
--
作者：
Laurent, S.;Vander Elst, L.;Muller, R. N.
通讯作者：
Muller, R. N.
影响因子：
4.9
作者：
Fulton, DA;Elemento, EM;Parker, D
通讯作者：
Parker, D
影响因子：
--
作者：
Port, Marc;Raynal, Isabelle;Guy, Alain
通讯作者：
Guy, Alain