Combined Optical and MR Bioimaging Using Rare Earth Ion Doped NaYF₄ Nanocrystals

TLDR

Rare‑earth doped fluoride nanocrystals enable efficient up‑ and down‑conversion photoluminescence, providing an optical imaging modality. The authors synthesized 20–30 nm NaYF₄ nanocrystals co‑doped with Gd³⁺ and Er³⁺/Yb³⁺/Eu³⁺, dispersed them in water, and functionalized them with anti‑claudin‑4 or anti‑mesothelin antibodies, enabling two‑photon up‑conversion imaging and targeted delivery to cancer cells. The study demonstrates that these nanoprobes provide dual‑modality optical and MR imaging, with in vivo optical imaging capability and strong T1/T2 contrast from Gd³⁺ co‑doping.

Abstract

Abstract Here, novel nanoprobes for combined optical and magnetic resonance (MR) bioimaging are reported. Fluoride (NaYF 4 ) nanocrystals (20–30 nm size) co‐doped with the rare earth ions Gd 3+ and Er 3+ /Yb 3+ /Eu 3+ are synthesized and dispersed in water. An efficient up‐ and downconverted photoluminescence from the rare‐earth ions (Er 3+ and Yb 3+ or Eu 3+ ) doped into fluoride nanomatrix allows optical imaging modality for the nanoprobes. Upconversion nanophosphors (UCNPs) show nearly quadratic dependence of the photoluminescence intensity on the excitation light power, confirming a two‐photon induced process and allowing two‐photon imaging with UCNPs with low power continuous wave laser diodes due to the sequential nature of the two‐photon process. Furthermore, both UCNPs and downconversion nanophosphors (DCNPs) are modified with biorecognition biomolecules such as anti‐claudin‐4 and anti‐mesothelin, and show in vitro targeted delivery to cancer cells using confocal microscopy. The possibility of using nanoprobes for optical imaging in vivo is also demonstrated. It is also shown that Gd 3+ co‐doped within the nanophosphors imparts strong T1 (Spin‐lattice relaxation time) and T2 (spin‐spin relaxation time) for high contrast MR imaging. Thus, nanoprobes based on fluoride nanophosphors doped with rare earth ions are shown to provide the dual modality of optical and magnetic resonance imaging.