Recent progress in functionalized lanthanide oxide (Ln₂O₃) nanoparticles for tumor targeting, medical imaging, and therapy is reviewed. Among the medical imaging techniques, magnetic resonance imaging (MRI) is an important noninvasive imaging tool for tumor diagnosis due to its high spatial resolution and excellent imaging contrast, especially when contrast agents are used. However, commercially available low-molecular-weight MRI contrast agents exhibit several shortcomings, such as nonspecificity for the tissue of interest and rapid excretion in vivo. Recently, nanoparticle-based MRI contrast agents have become a hot research topic in biomedical imaging due to their high performance, easy surface functionalization, and low toxicity. Among them, functionalized Ln₂O₃ nanoparticles are applicable as MRI contrast agents for tumor-targeting and nontumor-targeting imaging and image-guided tumor therapy. Primarily, Gd₂O₃ nanoparticles have been intensively investigated as tumor-targeting T₁ MRI contrast agents. T₂ MRI is also possible due to the appreciable paramagnetic moments of Ln₂O₃ nanoparticles (Ln = Dy, Ho, and Tb) at room temperature arising from the nonzero orbital motion of 4f electrons. In addition, Ln₂O₃ nanoparticles are eligible as X-ray computed tomography contrast agents because of their high X-ray attenuation power. Since nanoparticle toxicity is of great concern, recent toxicity studies on Ln₂O₃ nanoparticles are also discussed.

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.

Magnetite nanoparticles (Fe₃O₄ NPs) have been intensively investigated because of their potential biomedical applications due to their high saturation magnetization. In this study, core–shell Fe₃O₄@C NPs (core = Fe₃O₄ NPs and shell = amorphous carbons, d_avg = 35.1 nm) were synthesized in an aqueous solution. Carbon coating terminated with hydrophilic –OH and –COOH groups imparted excellent biocompatibility and hydrophilicity to the NPs, making them suitable for biomedical applications. The Fe₃O₄@C NPs exhibited ideal relaxometric properties for T₂ magnetic resonance imaging (MRI) contrast agents (i.e., high transverse and negligible longitudinal water proton spin relaxivities), making them exclusively induce only T₂ relaxation. Their T₂ MRI performance as contrast agents was confirmed in vivo by measuring T₂ MR images in mice before and after intravenous injection.

In recent years, significant advances in enhancing the quantum yield (QY) of trivalent lanthanide (Ln³⁺) ion-based nanoparticles have been achieved through photosensitization, using host matrices or capping organic ligands as photosensitizers to absorb incoming photons and transfer energy to the Ln³⁺ ions. The Ln³⁺ ion-based nanoparticles possess several excellent fluorescent properties, such as nearly constant transition energies, atomic-like sharp transitions, long emission lifetimes, large Stokes shifts, high photostability, and resistance to photobleaching; these properties make them more promising candidates as next-generation fluorescence probes in the visible region, compared with other traditional materials such as organic dyes and quantum dots. However, their QYs are generally low and thus need to be improved to facilitate and extend their applications. Considerable efforts have been made to improve the QYs of Ln³⁺ ion-based nanoparticles through photosensitization. These efforts include the doping of Ln³⁺ ions into host matrices or capping the nanoparticles with organic ligands. Among the Ln³⁺ ion-based nanoparticles investigated in previous studies, this review focuses on those containing Eu³⁺, Tb³⁺, and Dy³⁺ ions with red, green, and yellow emission colors, respectively. The emission intensities of Eu³⁺ and Tb³⁺ ions are stronger than those of other Ln³⁺ ions; therefore, the majority of the reported studies focused on Eu³⁺ and Tb³⁺ ion-based nanoparticles. This review discusses the principles of photosensitization, several examples of photosensitized Ln³⁺ ion-based nanoparticles, and in vitro and in vivo biomedical fluorescent imaging (FI) applications. This information provides valuable insight into the development of Ln³⁺ ion-based nanoparticles with high QYs through photosensitization, with future potential applications in biomedical FI.

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.