Synthesis, Characterizations, and 9.4 Tesla T2 MR Images of Polyacrylic Acid-Coated Terbium(III) and Holmium(III) Oxide Nanoparticles

Abstract

Polyacrylic acid (PAA)-coated lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Tb and Ho) with high colloidal stability and good biocompatibility were synthesized, characterized, and investigated as a new class of negative (T2) magnetic resonance imaging (MRI) contrast agents at high MR fields. Their r2 values were appreciable at a 3.0 T MR field and higher at a 9.4 T MR field, whereas their r1 values were negligible at all MR fields, indicating their exclusive induction of T2 relaxations with negligible induction of T1 relaxations. Their effectiveness as T2 MRI contrast agents at high MR fields was confirmed from strong negative contrast enhancements in in vivo T2 MR images at a 9.4 T MR field after intravenous administration into mice tails.

Functionalized Lanthanide Oxide Nanoparticles for Tumor Targeting, Medical Imaging, and Therapy

“…Nanoparticle contrast agents possess an additional advantage over molecular agents because cancer-targeting ligands and drugs can be easily attached to the nanoparticle surfaces. Small molecular ligands are less efficient in providing good colloidal stability to nanoparticles compared with polymer ligands, which is due to the presence of many hydrophilic binding groups in the polymers for attachment to the nanoparticles [39][40][41][42][43]. In addition, hydrophilic polymers can provide higher r 1 values than small molecular ligands [39][40][41] because they can attract more water molecules around the nanoparticles.…”

“…The imaging properties of nanoparticles depend on their particle and hydrodynamic diameters. Ln 2 O 3 nanoparticles synthesized via the polyol method generally have ultrasmall diameters (average particle diameter = 2.0 nm) [39][40][41][42][43][44]. Figure 4a-c shows various HRTEM images of Gd 2 O 3 nanoparticles [44,47,48].…”

“…To obtain high r 1 and r 2 values for enhanced MR contrast images, the nanoparticles must exhibit large M values at room temperature [59,60]. Figure 8a,b shows the M-H curves of Ln 2 O 3 nanoparticles (Ln = Gd, Tb, Ho) [41,43]. Similar to the corresponding bulk materials [61][62][63], all of the nanoparticle samples are paramagnetic (i.e., no hysteresis, zero coercivity, zero remanence, and low M values) and exhibit appreciable unsaturated M values up to the measured H values at 300 K. From the mass-corrected M-H curve, the net M value of the Gd 2 O 3 nanoparticles, which corresponds to the nanoparticles without ligands, at 2.0 T was estimated to be 1.71 emu/g.…”

“…Therefore, these nanoparticles are expected to provide appreciable T2 MR contrast images at high MR fields. For example, PAA-coated Ln2O3 nanoparticles (Ln = Tb and Ho) exhibit appreciable T2 MR contrast images at 9.4 T MR Field [43]. For comparison, this T2 contrast is lower than that of superparamagnetic iron oxide nanoparticles possessing high saturation magnetizations (50-80 emu/g) and high r2 values [67,68].…”

“…Recently, Ln2O3 (Ln = Tb, Dy, and Ho) nanoparticles with appreciable r2 and negligible r1 values, suitable for T2 MRI were developed [42,43,50,66,79,80]. For example, PAAcoated Ln2O3 (Ln = Tb and Ho) nanoparticles exhibited appreciable r2 values at 3.…”