Core-multi-shell design: unlocking multimodal capabilities in lanthanide-based nanoparticles as upconverting, -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:Yb,Er/NaGdF/NaDyF core/shell/shell nanoparticles (Dy-CSS NPs) and demonstrated their optical/-weighted MRI/CT multimodal capabilities. A known drawback of multimodal probes that merge the upconverting Er/Yb ion pair with magnetic Dy ions for -weighted MRI is the loss of upconversion (UC) emission due to Dy poisoning. Particular attention was paid to controlled nanoparticle architectures with tuned inner shell thicknesses separating Dy and Er/Yb to shed light on the distance-dependent loss of UC due to Yb → Dy energy transfer. Based on the Er UC spectra and the excited state lifetime of Yb, a 4 nm thick NaGdF inner shell did not only restore but enhanced the UC emission. We further investigated the effect of the outer NaDyF shell thickness on the particles' magnetic and CT performance. MRI relaxivity measurements 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 value, with a superior contrast effect compared to commercial iron oxide and other Dy-based contrast agents. In addition, the citrate-capped Dy-CSS NPs were demonstrated suitable for CT in imaging phantoms at X-ray energies of 110 keV, rendering them interesting alternatives to clinically used iodine-based agents that operate at lower energies.