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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.

diagnostics

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