Design, synthesis, physical and chemical characterisation, and biological interactions of lectin-targeted latex nanoparticles bearing Gd-DTPA chelates:: an exploration of magnetic resonance molecular imaging (MRMI)
Design, synthesis, physical and chemical characterisation, and biological interactions of lectin-targeted latex nanoparticles bearing Gd-DTPA chelates:: an exploration of magnetic resonance molecular imaging (MRMI)
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DOI：
10.1007/s00418-005-0780-7
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发表时间：
2005-03-01
影响因子：
2.3
通讯作者：
Debbage, P
中科院分区：
文献类型：
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作者：
Paschkunova-Martic, I;Kremser, C;Debbage, P
本次试点研究探索了用于磁共振分子成像（MRMI）的生物特异性靶向纳米颗粒造影剂的设计和合成所涉及的物理和化学参数。直径为 100、400 和 900 nm 的乳胶纳米粒子经过双重衍生，首先用番茄凝集素，然后用钆 (III)-二亚乙基三胺五乙酸（Gd 螯合物）将其靶向上皮和内皮糖萼 N-聚糖，并在磁共振成像 (MRI) 中产生对比度增强。静脉注射到小鼠、人胎盘子叶或人大隐静脉后，在 1.5T MRI 中获得血管结构的对比图像，成像平面的空间分辨率为 0.1 mm，z 轴的空间分辨率为 0.6 mm，持续时间 > 60 分钟，并且不会被缓冲液冲洗冲洗掉。纳米颗粒的超微结构分析揭示了纳米颗粒表面的靶向基团以及纳米颗粒内 Gd 螯合物的分布，并使计数能够用于确定弛豫率。所揭示的弛豫度值非常高，这是观察到强 MR 信号的原因。有时，大于 100 nm 的纳米颗粒与细胞膜或细胞外基质中胶原纤维的破坏区域存在紧密的空间关联。数据表明，100 nm 纳米颗粒可以为 MRMI 产生足够的对比度，并且对内皮细胞表面的破坏最小。
The physical and chemical parameters involved in the design and synthesis of biospecifically targeted nanoparticulate contrast media for magnetic resonance molecular imaging (MRMI) were explored in this pilot investigation. Latex nanoparticles 100, 400 and 900 nm in diameter were doubly derivatised, first with tomato lectin and then with gadolinium(III)-diethylenetriamine pentaacetic acid (Gd-chelates) to target them to epithelial and endothelial glycocalyceal N-glycans and to generate contrast enhancement in magnetic resonance imaging (MRI). After intravenous injection into mice, human placental cotyledons or human Vena saphena magna, contrasty images of the vascular structures were obtained in 1.5 T MRI with spatial resolution 0.1 mm in the imaging plane and 0.6 mm in the z axis, persisting > 60 min and resistant to washing out by buffer rinses. Ultrastructural analysis of the nanoparticles revealed the targeting groups at the nanoparticle surfaces and the distribution of the Gd-chelates within the nanoparticles and enabled counts for use in determining relaxivity. The relaxivity values revealed were extremely high, accounting for the strong MR signals observed. Occasionally, nanoparticles larger than 100 nm were seen in close spatial association with disrupted regions of cell membrane or of collagen fibrils in the extracellular matrix. The data suggest that 100-nm nanoparticles generate adequate contrast for MRMI and cause least disruption to endothelial cell surfaces.