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

被引：83

作者：

Chen, Kuan-Ju ^{[1
]}

Wolahan, Stephanie M. ^{[2
]}

Wang, Hao ^{[1
]}

Hsu, Chao-Hsiung ^{[3
,4
]}

Chang, Hsing-Wei ^{[5
]}

Durazo, Armando ^{[2
]}

Hwang, Lian-Pin ^{[5
]}

Garcia, Mitch A. ^{[1
]}

Jiang, Ziyue K. ^{[6
]}

Wu, Lily ^{[6
]}

Lin, Yung-Ya ^{[2
]}

Tseng, Hsian-Rong ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Calif NanoSyst Inst CNSI, Crump Inst Mol Imaging CIMI, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[3] Natl Tsing Hua Univ, Dept Chem, Hsinchu, Taiwan

[4] Acad Sinica, Inst Atom & Mol Sci, Mol Sci & Technol Program, Taiwan Int Grad Program, Taipei 10617, Taiwan

[5] Natl Taiwan Univ, Dept Chem, Taipei 10764, Taiwan

[6] Univ Calif Los Angeles, Dept Med & Mol Pharmacol, Los Angeles, CA 90095 USA

来源：

BIOMATERIALS | 2011年 / 32卷 / 08期

关键词：

Supramolecular Chemistry; Cyclodextrin; T1-weighted Contrast Agent; MRI; Gadolinium; Dynamic imaging; SILICA NANOPARTICLES; POLYAMINO-ACIDS; LIPOSOMES; DENDRIMERS; DISEASE; SYSTEM; MOTION;

D O I：

10.1016/j.biomaterials.2010.11.043

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页码：2160 / 2165

页数：6

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