Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd<sub>2</sub>O<sub>3</sub> Nanoparticles to Obtain a High r<sub>1</sub> Value and T<sub>1</sub> MR Images
Yeong-Ji Jang,
Shuwen Liu,
Huan Yue,
Ji Ae Park,
Hyunsil Cha,
Son Long Ho,
Shanti Marasini,
Adibehalsadat Ghazanfari,
Mohammad Yaseen Ahmad,
Xu Miao,
Tirusew Tegafaw,
Kwon-Seok Chae,
Yongmin Chang,
Gang Ho Lee
Affiliations
Yeong-Ji Jang
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Shuwen Liu
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Huan Yue
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Ji Ae Park
Division of Applied RI, Korea Institute of Radiological & Medical Sciences (KIRAMS), Seoul 01812, Korea
Hyunsil Cha
Department of Molecular Medicine, School of Medicine, Kyungpook National University, Taegu 41944, Korea
Son Long Ho
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Shanti Marasini
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Adibehalsadat Ghazanfari
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Mohammad Yaseen Ahmad
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Xu Miao
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Tirusew Tegafaw
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
Kwon-Seok Chae
Department of Biology Education, Teachers’ College, Kyungpook National University, Taegu 41566, Korea
Yongmin Chang
Department of Molecular Medicine, School of Medicine, Kyungpook National University, Taegu 41944, Korea
Gang Ho Lee
Department of Chemistry, College of Natural Sciences, Kyungpook National University, Taegu 41566, Korea
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) (Mw = ~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 (davg = 1.8 nm and aavg = 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.
