Abstract
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.
Highlights
Magnetic resonance imaging (MRI) is a noninvasive imaging method that provides high-resolution three-dimensional images of the body [1]
The mice survived after in vivo MRI experiments, thereby confirming the good biocompatibility of the synthesized nanoparticles. These results further indicate that the poly(acrylic acid-co-maleic acid) (PAAMA)-coated ultrasmall Gd2O3 nanoparticles are a potential T1 MRI contrast agent
Many water molecules interacted with many Gd3+ on the nanoparticle surface, achieving an extremely high r1 value based on the inner-sphere model [2,3]
Summary
Magnetic resonance imaging (MRI) is a noninvasive imaging method that provides high-resolution three-dimensional images of the body [1]. Because it affords substantially good image contrasts for the brain and soft tissues, MRI is preferred for diagnosis of the brain and soft tissues. Contrast agents enhance the image resolution and sensitivity of MRI by increasing the contrast [2,3,4] They can facilitate the early diagnosis of diseases. Gd3+-chelates are the most utilized T1 MRI contrast agents for clinical applications [2,3] These chelates possess low longitudinal water proton relaxivity (r1) values (3 to 5 s−1mM−1) because they can only interact with one water molecule [2,3]. As demonstrated by various types of ultrasmall nanoparticle systems [10,11,12], ultrasmall Gd2O3 nanoparticles can be excreted through the renal system to molecular agents, which are essential for in vivo applications
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