Functionalizing NaGdF4:Yb,Er Upconverting Nanoparticles with Bone-Targeting Phosphonate Ligands: Imaging and In Vivo Biodistribution

Abstract

Lanthanide-doped upconverting nanoparticles (UCNPs) transform near infrared light (NIR) into higher-energy UV and visible light by multiphotonic processes. Owing to such unique feature, UCNPs have found application in optical imaging and have been investigated for the NIR light activation of prodrugs, including transition metal complexes of interest in photochemotherapy. Besides, UCNPs also function as magnetic resonance imaging (MRI) contrast agents and positron emission tomography (PET) probes when labelled with radionuclides such as 18F. In this contribution, we report on a new series of phosphonate-functionalized NaGdF4:Yb,Er UCNPs that show affinity for hydroxyapatite (inorganic constituent of bones), and we discuss their potential as bone targeting multimodal (MRI/PET) imaging agents. In vivo biodistribution studies of 18F-labelled NaGdF4:Yb,Er UCNPs in rats indicate that surface functionalization with phosphonates favours the accumulation of nanoparticles in bones over time. PET results reveal leakage of 18F− for phosphonate-functionalized NaGdF4:Yb,Er and control nanomaterials. However, Gd was detected in the femur for phosphonate-capped UCNPs by ex vivo analysis using ICP-MS, corresponding to 6–7% of the injected dose.

Highly colloidally stable trimodal 125I-radiolabeled PEG-neridronate-coated upconversion/magnetic bioimaging nanoprobes

“…This stability was higher than that of cancer cell membrane-coated NaGdF 4 :Yb,Tm@NaGdF 4 particles, which were stable in PBS for only 3 days 58 . Additional advantage of phosphonate-functionalized NaGdF 4 :Yb/Er UCNPs consists in their enhanced accumulation in bones, which could be helpful for treatment and imaging of bone diseases 59 . Upconversion photoluminescence measurements of the NaGdF 4 :Yb 3+ /Er 3+ and NaGdF 4 :Yb 3+ /Tm 3+ nanoparticles confirmed the characteristic strong green/red (520, 540, and 650 nm) and UV/blue/NIR emissions (447, 473, and 800 nm).…”

Radiolabelling of nanomaterials for medical imaging and therapy

“…18C) found during in vivo studies strongly suggest radiochemical instability ([ 18 F]F-fluoride is known to accumulate in bone, Table 5). [198][199][200][201] Heterogenous exchange has been used on the radiolabelling of iron oxide NPs (IONPs) with 68 Ga, quantum dots (QDs) with 68 Ga and 64 Cu and UCNPs with 153 Sm. [202][203][204][205] The method provided radiolabelled NPs with high RCY and purity.…”

Assessing the protective effects of different surface coatings on NaYF4:Yb3+, Er3+ upconverting nanoparticles in buffer and DMEM

“…This includes multiphotonic excitation in the near-infrared (NIR) region 1 – 6 , emission of a multitude of characteristic narrow emission bands at shorter (upconversion luminescence, UCL) and longer (downshifted luminescence, DSL) wavelengths than the exciting photons 7 , long luminescence lifetimes 8 , and a high photostability 7 . These properties make them attractive fluorescent reporters for life sciences applications such as bioimaging 9 , 10 , in-vitro and in-vivo detection of biomolecules 11 – 14 , drug delivery 15 , photodynamic therapy 2 , 9 , 10 , 16 , and biosensing 2 , 3 . Utilization in bioimaging and cellular studies requires, however, biocompatible particles that are sufficiently stable in diluted dispersions and have no acute or chronic toxicity under application-relevant conditions 17 – 21 .…”