Manipulating the surface coating of ultra-small Gd₂O₃ nanoparticles for improved T₁-weighted MR imaging

In this report, monodispersed ultra-small Gd₂O₃ nanoparticles capped with hydrophobic oleic acid (OA) were synthesized with average particle size of 2.9nm. Two methods were introduced to modify the surface coating to hydrophilic for bio-applications. With a hydrophilic coating, the polyvinyl pyrrolidone (PVP) coated Gd₂O₃ nanoparticles (Gd₂O₃-PVP) showed a reduced longitudinal T₁ relaxation time compared with OA and cetyltrimethylammonium bromide (CTAB) co-coated Gd₂O₃ (Gd₂O₃-OA-CTAB) in the relaxation study. The Gd₂O₃-PVP was thus chosen for its further application study in MRI with an improved longitudinal relaxivity r₁ of 12.1mm^-1s^-1 at 7T, which is around 3 times as that of commercial contrast agent Magnevist^®. Invitro cell viability in HK-2 cell indicated negligible cytotoxicity of Gd₂O₃-PVP within preclinical dosage. Invivo MR imaging study of Gd₂O₃-PVP nanoparticles demonstrated considerable signal enhancement in the liver and kidney with a long blood circulation time. Notably, the OA capping agent was replaced by PVP through ligand exchange on the Gd₂O₃ nanoparticle surface. The hydrophilic PVP grants the Gd₂O₃ nanoparticles with a polar surface for bio-application, and the obtained Gd₂O₃-PVP could be used as an invivo indicator of reticuloendothelial activity.