RGD-functionalized ultrasmall iron oxide nanoparticles for targeted T1-weighted MR imaging of gliomas

Abstract

We report a convenient approach to prepare ultrasmall Fe₃O₄ nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe₃O₄ NPs were prepared by a solvothermal route. Then, the carboxylated Fe₃O₄ NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe₃O₄-PEG-RGD) was fully characterized using different techniques. We show that these Fe₃O₄-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing α_vβ₃ integrin in vitro. With the relatively high r₁ relaxivity (r₁ = 1.4 mM⁻¹ s⁻¹), the Fe₃O₄-PEG-RGD particles can be used as an efficient nanoprobe for targeted T₁-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe₃O₄ NPs may hold great promise to be used as a nanoprobe for targeted T₁-weighted MR imaging of different α_vβ₃ integrin-overexpressing cancer cells or biological systems.