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.

Magnetic resonance imaging (MRI) is increasingly used to diagnose focal and diffuse liver disorders. Despite their enhanced efficacy, liver-targeted gadolinium-based contrast agents (GBCAs) raise safety concerns owing to the release of toxic Gd³⁺ ions. A π-conjugated macrocyclic chelate, Mn-NOTA-NP, was designed and synthesized as a non-gadolinium alternative for liver-specific MRI. Mn-NOTA-NP exhibits an r₁ relaxivity of 3.57 mM⁻¹ s⁻¹ in water and 9.01 mM⁻¹ s⁻¹ in saline containing human serum albumin at 3 T, which is significantly greater than the clinically utilized Mn²⁺-based hepatobiliary drug, Mn-DPDP (1.50 mM⁻¹ s⁻¹), and comparable with that of GBCAs. Furthermore, the in vivo biodistribution and MRI enhancement patterns of Mn-NOTA-NP were similar to those of the Gd³⁺-based hepatobiliary agent, Gd-DTPA-EOB. Additionally, a 0.05 mmol/kg dose of Mn-NOTA-NP facilitated high-sensitivity tumor detection with tumor signal enhancement in a liver tumor model. Ligand-docking simulations further indicated that Mn-NOTA-NP differed from other hepatobiliary agents in their interactions with several transporter systems. Collectively, we demonstrated that Mn-NOTA-NP could be a new liver-specific MRI contrast agent.

Water proton spin relaxivities, colloidal stability, and biocompatibility of nanoparticle magnetic resonance imaging (MRI) contrast agents depend on surface-coating ligands. In this study, hydrophilic and biocompatible polyethylenimines (PEIs) of different sizes (M_n = 1200 and 60,000 amu) were used as surface-coating ligands for ultrasmall holmium oxide (Ho₂O₃) nanoparticles. The synthesized PEI1200- and PEI60000-coated ultrasmall Ho₂O₃ nanoparticles, with an average particle diameter of 2.05 and 1.90 nm, respectively, demonstrated low cellular cytotoxicities, good colloidal stability, and appreciable transverse water proton spin relaxivities (r₂) of 13.1 and 9.9 s⁻¹mM⁻¹, respectively, in a 3.0 T MR field with negligible longitudinal water proton spin relaxivities (r₁) (i.e., 0.1 s⁻¹mM⁻¹) for both samples. Consequently, for both samples, the dose-dependent contrast changes in the longitudinal (R₁) and transverse (R₂) relaxation rate map images were negligible and appreciable, respectively, indicating their potential as efficient transverse T₂ MRI contrast agents in vitro.