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.

Keywords: Ho2O3; MRI; Tb2O3; high MR field; nanoparticles; polyacrylic acid-coating.

Figure 1

One-pot polyol synthesis of the PAA-coated Ln₂O₃ NPs (Ln = Tb and Ho).

Figure 2

(a) Photographs of nanoparticle suspension samples in aqueous media, 10% FBS in RPMI1640 medium, and sodium acetate buffer solution (pH = 7.0), (b) laser light scattering (i.e., Tyndall effect) proving NP dispersions: laser light scattering was observed only for both solution samples whereas no light scattering was observed for the reference triple-distilled water, (c) HRTEM images at low (10 nm scale) and high (2 nm scale) magnifications: dotted circles indicate the PAA-coated Ln₂O₃ NPs (Ln = Tb and Ho), (d) particle diameter distributions and log-normal function fits (the total number of NPs, N_total = 133 for PAA-coated Tb₂O₃ NPs and 111 for PAA-coated Ho₂O₃ NPs), (e) hydrodynamic diameter distributions and log-normal function fits, (f) plots of zeta potentials (ξ) overtime (0, 1, 2, and 4 days) [insets are plot of ξ versus time (t)], (g) plots of ΔT [= T(t) − T(0); T = height-averaged transmission of NIR beam] as a function of time, and (h) plots of ΔBST [= BST(t) − BST(0); BST = height-averaged backscattering of NIR beam] as a function of time. Labels “Tb” and “Ho” indicate the PAA-coated Tb₂O₃ and Ho₂O₃ NPs, respectively.

Figure 3

XRD patterns before (bottom spectra) and after TGA (top spectra) of the PAA-coated Ln₂O₃ NPs [Ln = (a) Tb and (b) Ho]. Only the intense peaks were representatively assigned with (hkl) Miller indices for the XRD patterns after TGA.

Figure 4

(a) FTIR absorption spectra of the powder samples and free PAA, (b) bridge-bonding structure of COO⁻ with Ln³⁺ on a NP surface (many such bridge-bonding structures exist per NP because of many COO⁻ groups per PAA and many Ln³⁺ on a NP surface), and (c) TGA curves of the powder samples: the numbers are the amounts of PAA-coating in wt.%. Labels (i) and (ii) indicate the PAA-coated Ln₂O₃ NPs [Ln = (i) Tb and (ii) Ho].

Figure 5

In vitro cell viabilities of NCTC1469 and DU145 cells incubated with the PAA-coated Ln₂O₃ NPs [Ln = (a) Tb and (b) Ho]. (c) Optical images of DU145 cancer cells incubated with PAA-coated Tb₂O₃ NPs at various Tb-concentrations.

Figure 6

M−H curves of the PAA-coated Ln₂O₃ NPs at 300 K [Ln = (i) Tb and (ii) Ho]. Net M values of the Ln₂O₃ NPs (i.e., without PAA) estimated from TGA curves were used in the plots.

Figure 7

Plots of 1/T₁ and 1/T₂ versus Ln-concentration at (a) 3.0 T and (b) 9.4 T. Labels (i) and (ii) indicate the PAA-coated Ln₂O₃ NPs [Ln = (i) Tb and (ii) Ho].

Figure 8

In vivo T₂ MR images of the liver and kidneys at 3.0 and 9.4 T MR fields before (=Pre) and 15 (or 16) min after intravenous administration of aqueous suspension samples of the PAA-coated Ln₂O₃ NPs into mice tails [Ln = (a) Tb and (b) Ho]. SNR plots of ROI as a function of time (0 = Pre) at 3.0 and 9.4 T MR fields for the PAA-coated Ln₂O₃ NPs [Ln = (c) Tb and (d) Ho]. Labels at each first MR image on the left: ROI = small dotted circles; L = liver; K = kidney.

Figure 9

Scheme explaining the ligand-size effects on hydrodynamic diameter and r₂ value. a_avg and a_avg’ = average hydrodynamic diameter; B and B’ = magnetic field generated by the NP.