title: Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles.
abstract: 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.
authors: The Key Laboratory of Resource Chemistry of Ministry of Education, College of Life and Environmental Science, Shanghai Normal University, Shanghai, PR China.
authors: Hong
authors: H
authors: Yang
authors: Yeming
authors: Y
authors: Zhuang
authors: Yun
authors: Y
authors: Sun
authors: Antao
authors: A
authors: Dai
authors: Xiangyang
authors: X
authors: Shi
authors: Dongmei
authors: D
authors: Wu
authors: Fuyou
authors: F
authors: Li
authors: He
authors: H
authors: Hu
authors: Shiping
authors: S
authors: Yang
mesh_terms: D002460:Cell Line; D003287:Contrast Media / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008422:Materials Testing; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010316:Particle Size; D014961:X-Ray Diffraction
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D005682:Gadolinium