Encapsulation of Gadobutrol in AVE-based liposomal carriers for MR detectability
Encapsulation of Gadobutrol in AVE-based liposomal carriers for MR detectability
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DOI：
10.1016/j.mri.2004.01.039
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发表时间：
2004-05-01
影响因子：
2.5
通讯作者：
Alfke, H
中科院分区：
文献类型：
--
作者：
Heverhagen, JT;Graser, A;Alfke, H
人工病毒样包膜（AVE）是脂质体载体，可用于靶向部位特异性递送造影剂。我们推测，T-1弛豫时间的悬浮液钆填充AVE可能会缩短后，内化和溶酶体分解。为了验证这一假设，我们评估了含钆布醇的AVE在体外降解前后和受体介导的细胞摄取后的T-1弛豫时间。用1 M钆布醇（Gadovist; Schering AG，柏林，德国）填充AVE，产生Gd-螯合物-AVE。T-1-弛豫时间使用反转恢复技术计算不同浓度的脂质体悬浮液。体外降解AVE以模拟包封的钆在细胞中的释放，并确定T-1效应的推定增加。最后，在细胞摄取到内皮细胞或黑色素瘤细胞后，测定配备有整合素结合RGD配体的Gd-螯合物-AVE和这些Gd-螯合物-RDG-AVE的T-1弛豫时间。钆布醇可以在1 M的高浓度下包封到AVE中（Gd-螯合物-AVE）。MRI可显示Gd螯合物AVE。浓度降低到1：4 x 10（3）显示出显著的T-1缩短效应。用Triton X-100降解脂质体导致浓度进一步降低至1：10 x 10（3）。此外，Gd-螯合物-RGD-AVE的细胞摄取也导致显著的T-1缩短。我们的研究表明，钆可以有效地封装到AVE和Gd螯合物AVE可以检测到MRI的T-1加权测量。MRI可检测性因降解而增强。Gd-螯合物-RGD-AVE可用于增强表达α（v）β（3）受体的细胞中的Gd摄取。(C)2004年爱思唯尔公司All rights reserved.
Artificial virus-like envelopes (AVEs) are liposomal carriers that may be useful for target-site-specific delivery of contrast agents. We speculated that T-1 relaxation times of a suspension of Gadolinium-filled AVEs might be shortened after internalization and lysosomal breakdown. To test this hypothesis we evaluated the T-1 relaxation times of Gadobutrol-containing AVEs before and after degradation in vitro and after receptor-mediated cellular uptake. AVEs were filled with 1 M Gadobutrol (Gadovist; Schering AG, Berlin, Germany) yielding Gd-chelate-AVEs. T-1-relaxation times were calculated using an inversion recovery technique for different concentrations of the liposomal suspension. AVEs were degraded in vitro to mimic the release of the encapsulated Gadolinium in cells and to determine a putatitive increase of the T-1-effect. Finally, Gd-chelate-AVEs where equipped with integrin-binding RGD ligands and the T-1 relaxation times of these Gd-chelate-RDG-AVEs were determined after cellular uptake into endothelial or melanoma cells. Gadobutrol could be encapsulated into AVEs at a high concentration of 1 M (Gd-chelate-AVEs). The Gd-chelate-AVEs could be visualized by MRI. Concentrations down to 1:4 x 10(3) showed a significant T-1-shortening effect. The degradation of the liposomes with Triton X-100 resulted in a further reduction down to concentrations of 1:10 x 10(3). In addition, cellular uptakes of Gd-chelate-RGD-AVEs also lead to a significant T-1-shortening. Our study shows that Gadolinium can be efficiently encapsulated into AVEs and that Gd-chelate-AVEs can be detected by MRI T-1-weighted measurements. The MRI detectability is enhanced by degradation. Gd-chelate-RGD-AVEs can be used to enhance the Gd uptake in cells expressing the alpha(v)beta(3) receptor. (C) 2004 Elsevier Inc. All rights reserved.