Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles

Hong Yang, Yeming Zhuang, Yun Sun, Antao Dai, Xiangyang Shi, Dongmei Wu, Fuyou Li, He Hu, Shiping Yang
Biomaterials 2011, 32 (20): 4584-93
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 (Fe(3)O(4)@SiO(2) NPs) with a diameter of approximately 21 nm were synthesized via a thermal decomposition approach and were aminated through silanization. The amine-functionalized Fe(3)O(4)@SiO(2) 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 Fe(3)O(4)@SiO(2)(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 Fe(3)O(4)@SiO(2)(Gd-DTPA)-RGD NPs enable targeted dual-contrast T(1)- and T(2)-weighted MR imaging of tumor cells over-expressing high-affinity α(v)β(3) integrin in vitro and in vivo. Our results clearly indicate that the approach to forming multifunctional Fe(3)O(4)@SiO(2)(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.

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