RGD-Conjugated Nanoscale Coordination Polymers for Targeted T_(1-~) and T_(2~-)-weighted Magnetic Resonance Imaging of Tumors in Vivo

摘要

Development of multifunctional nanoscale coordination polymers (NCPs) allowing for T_(1~-) and T_(2~-)weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, nanoscale coordination polymers (NCPs) with a diameter of ≈80 nm are obtained with l,1′-dicarboxyl ferrocene (Fc) as building blocks and magnetic gadolinium(Ⅲ) ions as metallic nodes using a nanoprecipitation method, then further aminated through silanization. The amine-functionalized Fc-Cd@SiO_2 NCPs enable the covalent conjugation of a fluorescent rhoda-mine dye (RBITC) and an arginine-glycine-aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed water-dispersible Fc-Gd@ SiO_2(RBITC)-RCD NCPs exhibit a low cytotoxicity, as confirmed by MTT assay. They have a longitudinal relaxivity (r_1)) of 5.1 mM~(-1) s~(-1) and transversal relaxivity (r_2) of 21.7 mM~(-1) s~(-1) suggesting their possible use as both T_(1~-)positive and T_(2~-)negative contrast agents. In vivo MR imaging experiments show that the signal of tumor over-expressing high affinity α_vβ_3 integrin from T_(1~-)weighted MR imaging is positively enhanced 47±5%, and negatively decreased 33±5% from T_(2~-)weighted MR imaging after intravenous injection of Fc-Cd@SiO_2(RBITC)-RCD NCPs.