A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity.

A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity.
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DOI:
10.1016/j.biomaterials.2010.11.043
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发表时间:
2011-03
期刊:
影响因子:
14
通讯作者:
Tseng, Hsian-Rong
Tseng, Hsian-Rong
中科院分区:
工程技术1区
文献类型:
--
作者:
Chen, Kuan-Ju;Wolahan, Stephanie M.;Wang, Hao;Hsu, Chao-Hsiung;Chang, Hsing-Wei;Durazo, Armando;Hwang, Lian-Pin;Garcia, Mitch A.;Jiang, Ziyue K.;Wu, Lily;Lin, Yung-Ya;Tseng, Hsian-Rong

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我们通过包封顺磁性螯合钆(III)引入了一类新的基于纳米颗粒的T1 MRI造影剂(CA),即,Gd 3+·DOTA,通过携带互补分子识别基序的分子构建块的超分子组装,包括金刚烷(Ad)和β-环糊精(CD)。通过系统地改变分子构建块的混合比例,制备了小的Gd 3+·DOTA包封的超分子纳米颗粒(Gd 3+·DOTA-SNPs)库。宽范围的弛豫速率与所得的Gd 3+·DOTA SNP文库相关。因此,Gd 3+·DOTA的最佳合成配方是r1为17.3 s-1 mM-1(约1000)的SNP。4-在高场强下比临床Gd 3+螯合复合物高1倍)。Gd 3+·DOTA SNP的T1加权成像显示出增强的灵敏度,其对比噪声比(C/N比)约为1.5。3.6比游离Gd ~(3+)·DTPA高10倍。将Gd 3+·DOTA双SNP溶液注射到小鼠的足垫中,并且使用MRI来监测基于Gd 3+·DOTA双SNP的CA的动态淋巴引流。我们在T1加权成像中观察到注射Gd 3+·DOTA SNPs后肱淋巴结信号强度增加,但注射Gd 3+·DTPA后没有。MRI结果得到离体ICP-MS分析的支持。这些结果表明,Gd 3+·DOTA双核苷酸单核苷酸多态性不仅表现出增强的弛豫能力和高灵敏度,而且可以作为诊断癌症转移的潜在工具。
We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA⊂SNPs with an r1 of 17.3 s−1mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+·DTPA. A Gd3+·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA⊂SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.
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