Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd 2 O 3 Nanoparticles to Obtain a High r 1 Value and T 1 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 = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd O ) 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 Gd O nanoparticles (d = 1.8 nm and a = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r ) of 40.6 s mM (r /r = 1.56, where r = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd O nanoparticles as a T MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T MR images at the 3.0 T MR field.