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

We introduce a new category of nanoparticle-based T-1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(111), i.e., Gd3+ DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and p-cyclodextrin (CD). A small library of Gd3+. DOTA-encapsulated supramolecular nanoparticles (Gd3+.DOTA subset of 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 subset of SNP library. Consequently, an optimal synthetic formulation of Gd3+.DOTA subset of SNPs with an r(1) of 17.3 s(-1) mM(-1) (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T-1-weighted imaging of Gd3+.DOTA subset of 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 subset of SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+.DOTA subset of SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in Ti-weighted imaging after injecting Gd3+.DOTA subset of SNPs but not after injecting Gd3+.DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+.DOTA subset of SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. (C) 2010 Elsevier Ltd. All rights reserved.