Core-multi-shell design: unlocking multimodal capabilities in lanthanide-based nanoparticles as upconverting, T 2 -weighted MRI and CT probes.

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)-NaGdF 4 :Yb,Er/NaGdF 4 /NaDyF 4 core/shell/shell nanoparticles (Dy-CSS NPs) and demonstrated their optical/ T 2 -weighted MRI/CT multimodal capabilities. A known drawback of multimodal probes that merge the upconverting Er 3+ /Yb 3+ ion pair with magnetic Dy 3+ ions for T 2 -weighted MRI is the loss of upconversion (UC) emission due to Dy 3+ poisoning. Particular attention was paid to controlled nanoparticle architectures with tuned inner shell thicknesses separating Dy 3+ and Er 3+ /Yb 3+ to shed light on the distance-dependent loss of UC due to Yb 3+ → Dy 3+ energy transfer. Based on the Er 3+ UC spectra and the excited state lifetime of Yb 3+ , a 4 nm thick NaGdF 4 inner shell did not only restore but enhanced the UC emission. We further investigated the effect of the outer NaDyF 4 shell thickness on the particles' magnetic and CT performance. MRI T 2 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 r 2 value, with a superior T 2 contrast effect compared to commercial iron oxide and other Dy-based T 2 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.