The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s−1mM−1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

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 (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 (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 (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.

Nanoparticles are considered potential candidates for a new class of magnetic resonance imaging (MRI) contrast agents. Negative MRI contrast agents require high magnetic moments. However, if nanoparticles can exclusively induce transverse water proton spin relaxation with negligible induction of longitudinal water proton spin relaxation, they may provide negative contrast MR images despite having low magnetic moments, thus acting as an efficient T₂ MRI contrast agent. In this study, carbon-coated paramagnetic dysprosium oxide (DYO@C) nanoparticles (core = DYO = Dy_xO_y; shell = carbon) were synthesized to explore their potential as an efficient T₂ MRI contrast agent at 3.0 T MR field. Since the core DYO nanoparticles have an appreciable (but not high) magnetic moment that arises from fast 4f-electrons of Dy(III) (⁶H_15/2), the DYO@C nanoparticles exhibited an appreciable transverse water proton spin relaxivity (r₂) with a negligible longitudinal water proton spin relaxivity (r₁). Consequently, they acted as a very efficient T₂ MRI contrast agent, as proven from negative contrast enhancements seen in the in vivo T₂ MR images.

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.

Surface-coating polymers contribute to nanoparticle-based magnetic resonance imaging (MRI) contrast agents because they can affect the relaxometric properties of the nanoparticles. In this study, polyaspartic acid (PASA)-coated ultrasmall Gd₂O₃ nanoparticles with an average particle diameter of 2.0 nm were synthesized using the one-pot polyol method. The synthesized nanoparticles exhibited r₁ and r₂ of 19.1 and = 53.7 s⁻¹mM⁻¹, respectively, (r₁ and r₂ are longitudinal and transverse water–proton spin relaxivities, respectively) at 3.0 T MR field, approximately 5 and 10 times higher than those of commercial Gd-chelate contrast agents, respectively. The T₁ and T₂ MR images could be obtained due to an appreciable r₂/r₁ ratio of 2.80, indicating their potential as a dual-modal T₁ and T₂ MRI contrast agent.

Ultrasmall nanoparticles are potential candidates for application as high-performance imaging agents. Herein, we present the synthesis and characterization of folic acid (FA)-conjugated polyacrylic acid (PAA)-coated MnO nanoparticles with an average particle diameter of 2.7 nm. FA conferred cancer-targeting ability, while PAA conferred good colloidal stability and low cellular cytotoxicity on the FA-PAA-coated MnO nanoparticles. Further, the nanoparticles exhibited a high relaxivity (r₁) value of 9.3 s⁻¹mM⁻¹ (r₂/r₁ = 2.2). Their application potential as cancer-targeting T₁ magnetic resonance imaging contrast agents was confirmed by their enhanced T₁ contrast enhancements at the brain cancer (U87MG) site upon intravenous administration to mice tails.