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(w) = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd(2)O(3)) 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(2)O(3) 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 (r(1)) of 40.6 s(−1)mM(−1) (r(2)/r(1) = 1.56, where r(2) = 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(2)O(3) nanoparticles as a T(1) MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T(1) MR images at the 3.0 T MR field.