Hydrophilic biocompatible poly(Acrylic acid-co-maleic acid) polymer as a surface-coating ligand of ultrasmall Gd₂O₃ nanoparticles to obtain a high R₁ value and T₁ Mr images

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (M_w = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd₂O₃) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd₂O₃ nanoparticles (d_avg = 1.8 nm and a_avg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r₁) of 40.6 s⁻¹mM⁻¹ (r₂/r₁ = 1.56, where r₂ = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd₂O₃ nanoparticles as a T₁ MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T₁ MR images at the 3.0 T MR field.