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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
Biomaterials, 03/2011, Letnik: 32, Številka: 8Journal Article
Abstract 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−1 mM−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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