Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), Crump Institute for Molecular Imaging (CIMI), University of California, Los Angeles, 570 Westwood Plaza, Building 114, Los Angeles, CA 90095-1770, USA.
Biomaterials. 2011 Mar;32(8):2160-5. doi: 10.1016/j.biomaterials.2010.11.043. Epub 2010 Dec 16.
We introduce a new category of nanoparticle-based T(1) MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd(3+)·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 Gd(3+)·DOTA-encapsulated supramolecular nanoparticles (Gd(3+)·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd(3+)·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd(3+)·DOTA⊂SNPs with an r(1) of 17.3 s(-1) mM(-1) (ca. 4-fold higher than clinical Gd(3+) chelated complexes at high field strengths) was identified. T(1)-weighted imaging of Gd(3+)·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 Gd(3+)·DTPA. A Gd(3+)·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd(3+)·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T(1)-weighted imaging after injecting Gd(3+)·DOTA⊂SNPs but not after injecting Gd(3+)·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd(3+)·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.
我们通过超分子组装，将顺磁螯合钆（III），即 Gd（3+）·DOTA，封装在具有互补分子识别基序的分子构建块中，从而引入了一类新型基于纳米粒子的 T（1）MRI 造影剂（CAs）。我们通过系统地改变分子构建块的混合比例，制备了一个由 Gd（3+）·DOTA 封装的超分子纳米颗粒（Gd（3+）·DOTA⊂SNPs）的小文库。我们将得到的 Gd（3+）·DOTA⊂SNP 文库与广泛的弛豫率相关联。因此，我们确定了 Gd（3+）·DOTA⊂SNPs 的最佳合成配方，其 r（1）为 17.3 s(-1) mM(-1)（在高场强下约比临床 Gd（3+）螯合复合物高 4 倍）。Gd（3+）·DOTA⊂SNPs 的 T（1）加权成像表现出增强的灵敏度，其对比噪声比（C/N 比）比观察到的游离 Gd（3+）·DTPA 高约 3.6 倍。将 Gd（3+）·DOTA⊂SNPs 溶液注入小鼠的脚掌，并用 MRI 监测 Gd（3+）·DOTA⊂SNPs 基 CA 的动态淋巴引流。在注射 Gd（3+）·DOTA⊂SNPs 后，我们观察到 T（1）加权成像中臂淋巴结的信号强度增加，但在注射 Gd（3+）·DTPA 后则没有。这些 MRI 结果得到了 ICP-MS 分析的支持。这些结果表明，Gd（3+）·DOTA⊂SNPs 不仅表现出增强的弛豫率和高灵敏度，而且可以作为诊断癌症转移的潜在工具。
