期刊
BIOMATERIALS
卷 32, 期 20, 页码 4584-4593出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.03.018
关键词
Dual-contrast; Targeted; Tumors; Magnetic resonance imaging; Gadolinium-labeled; Superparamagnetic iron oxide
资金
- National Natural Science Foundation of China [20971086, 50802059, 20825101]
- Shanghai Key Laboratory of the Rare Earth Functional Materials [07dz22303]
- Shanghai Pujiang Program [09PJ1400600]
- Shanghai Municipal Education Commission [10ZZ84]
- Shanghai Rising-Star Program [09QA1404300]
- Shanghai Leading Academic Discipline Project [B108]
Development of a multifunctional nanoparticle (NP) system allowing for dual-contrast T-1- and T-2-weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, superparamagnetic silica-coated iron oxide core-shell nanoparticles (Fe3O4@SiO2 NPs) with a diameter of approximately 21 nm were synthesized via a thermal decomposition approach and were aminated through silanization. The amine-functionalized Fe3O4@SiO2 NPs enabled the covalent conjugation of a paramagnetic gadolinium complex (Gd-DTPA, DTPA: diethylenetriamine pentaacetic acid) and an arginine-glycine-aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed Fe3O4@SiO2(Gd-DTPA)-RGD NPs are water-dispersible, stable, and biocompatible as confirmed by MTT cell viability assay. Relaxivity measurements show that they have a T-1 relaxivity (r(1)) of 4.2 mM(-1) s(-1) and T-2 relaxivity (r(2)) of 17.4 mM(-1) s(-1) at the Gd/Fe molar ratio of 0.3:1, suggesting a possibility to use them as both T-1 positive and T-2 negative contrast agents. In vitro and in vivo MR imaging experiments show that the developed multifunctional Fe3O4@SiO2(Gd-DTPA)-RGD NPs enable targeted dual-contrast T-1- and T-2-weighted MR imaging of tumor cells over-expressing high-affinity alpha(v)beta(3) integrin in vitro and in vivo. Our results clearly indicate that the approach to forming multifunctional Fe3O4@SiO2(Gd-DTPA)-RGD NPs could be extended for fabricating other biologically active NPs for T-1- and T-2-weighted MR imaging of other biological systems with high accuracy. (C) 2011 Elsevier Ltd. All rights reserved.
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