Core–multi-shell design: unlocking multimodal capabilities in lanthanide-based nanoparticles as upconverting, T2-weighted MRI and CT probes

Abstract

Multimodal bioimaging probes merging optical imaging, magnetic resonance imaging (MRI), and X-ray computed tomography (CT) capabilities have attracted considerable attention due to their potential biomedical applications. Lanthanide-based nanoparticles are promising candidates for multimodal imaging because of their optical, magnetic and X-ray attenuation properties. We prepared a set of hexagonal-phase (β)-NaGdF₄:Yb,Er/NaGdF₄/NaDyF₄ core/shell/shell nanoparticles (Dy-CSS NPs) and demonstrated their optical/T₂-weighted MRI/CT multimodal capabilities. A known drawback of multimodal probes that merge the upconverting Er³⁺/Yb³⁺ ion pair with magnetic Dy³⁺ ions for T₂-weighted MRI is the loss of upconversion (UC) emission due to Dy³⁺ poisoning. Particular attention was paid to controlled nanoparticle architectures with tuned inner shell thicknesses separating Dy³⁺ and Er³⁺/Yb³⁺ to shed light on the distance-dependent loss of UC due to Yb³⁺ → Dy³⁺ energy transfer. Based on the Er³⁺ UC spectra and the excited state lifetime of Yb³⁺, a 4 nm thick NaGdF₄ inner shell did not only restore but enhanced the UC emission. We further investigated the effect of the outer NaDyF₄ shell thickness on the particles’ magnetic and CT performance. MRI T₂ relaxivity measurements in vitro at a magnetic field of 7 T performed on citrate-capped Dy-CSS NPs revealed that NPs with the thickest outer shell thickness (4 nm) exhibited the highest r₂ value, with a superior T₂ contrast effect compared to commercial iron oxide and other Dy-based T₂ contrast agents. In addition, the citrate-capped Dy-CSS NPs were demonstrated suitable for CT in in vitro imaging phantoms at X-ray energies of 110 keV, rendering them interesting alternatives to clinically used iodine-based agents that operate at lower energies.