Paramagnetic Eu-doped Gd ₂ O ₃ nanoparticles for dual-modal MRI-FI imaging: unraveling cellular fluorescence imaging and impact of dopant concentration on MR relaxivity

In recent years, rare earth-doped gadolinium oxide (RE:Gd 2 O 3 ) nanoparticles (NPs) have captured the attention of biomedical researchers as potent contrast agents (CAs) to enhance the diagnostic accuracy of magnetic resonance imaging (MRI), while simultaneously enabling high sensitivity fluorescence imaging (FI). However, there remains a scarcity of studies demonstrating their successful utilization as dual-modal MRI-FI CAs. In this study, a series of paramagnetic gadolinium oxide (Gd 2 O 3 ) NPs doped with varying europium (Eu 3+ ) concentrations (0.5–10 M%) were synthesized using a low-temperature polyol-mediated route assisted by hydrogen peroxide (H 2 O 2 ). The influence of Eu 3+ doping concentration on crystallinity, phase, morphology, magnetic properties and MR relaxometric properties was investigated systematically. X-ray diffraction (XRD) analysis confirmed a cubic crystalline phase for both undoped and Eu-doped Gd 2 O 3 NPs. A systematic decrease in particle size was observed for Eu-doped Gd 2 O 3 with an increase in Eu 3+ concentration, which was further validated by transmission electron microscopy (TEM) imaging and could be attributed to dopant-induced lattice micro-strain. Fluorescence microscopy of human embryonic kidney (HEK) cells incubated with Eu-doped Gd 2 O 3 NPs revealed efficient cellular uptake and characteristic red emission arising from the Eu 3+ 5 D 0 → 7 F 2 transition, confirming their FI capability. MRI relaxometric measurements revealed a significant increase in longitudinal ( r 1 ) relaxivity for Eu-doped Gd 2 O 3 NPs with an increase in Eu 3+ dopant concentration. The longitudinal relaxivity has been found to be increased significantly from 5.88 s −1 mM −1 for undoped Gd 2 O 3 NPs to 9.17 s −1 mM −1 for 10 M% Eu-doped Gd 2 O 3 NPs, corresponding to an ∼55% improvement in MRI contrast efficiency. Overall, polyethylene glycol-200 (PEG200)-capped Eu-doped Gd 2 O 3 NPs, within the investigated particle-size regime, exhibit strong potential as bimodal CAs for MRI and FI.