Multifunctional Rare-Earth Element Nanocrystals for Cell Labeling and Multimodal Imaging

Abstract

In this work, we describe a simple solvothermal route for the synthesis of Eu³⁺-doped gadolinium orthovanadate nanocrystals (Eu:GdVO₄-PAA) functionalized with poly(acrylic)acid (PAA), that are applicable as cell labeling probes for multimodal cellular imaging. The Eu³⁺ doping of the vanadate matrix provides optical functionality, due to red photoluminescence after illumination with UV light. The Gd³⁺ ions of the nanocrystals reduce the T1 relaxation time of surrounding water protons, allowing these nanocrystals to act as a positive MRI contrast agent with a r1 relaxivity of 1.97 mM^-1 s^-1. Low background levels of Eu³⁺, Gd³⁺, and V⁵⁺ in biological systems make them an excellent label for elemental microscopy by Laser Ablation (LA)-ICP-MS. Synthesis resulted in polycrystalline nanocrystals with a hydrodynamic diameter of 55 nm and a crystal size of 36.7 nm, which were further characterized by X-ray diffraction (XRD), photoluminescence spectroscopy (PL) and transmission electron microscopy (TEM). The multifunctional nanocrystals were subsequently used for intracellular labeling of both human adipose-derived stem cells (MSCs) and A549 (adenocarcinomic human alveolar basal epithelial) cells.

Keywords: LA-ICP-MS; MRI; cell labeling probe; multimodal imaging; rare-earth element nanocrystals.