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

Silvia Alonso-De Castro,Luca Salassa,Daniel Padro,Unai Cossío,Jordi Llop,Zuriñe Baz,Aitor Lekuona Fernández,Vanessa Gómez-Vallejo,Emmanuel Ruggiero,Dorleta Otaegui

doi:10.3390/inorganics7050060

Silvia Alonso-De Castro, Luca Salassa + Show 8 more

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https://doi.org/10.3390/inorganics7050060

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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.

Highlights

In recent years, our group developed a number of unconventional approaches for the photoactivation of metal-based anticancer prodrug complexes [1,2,3], including the use of lanthanide-doped upconverting nanoparticles (UCNPs) as near infrared (NIR) light triggers [4,5,6]
We explored the potential of phosphonate-functionalized NaGdF4 :Yb,Er UCNPs to behave as magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging tools for bones, motivated by the long-term prospect of designing theranostic nanoconstructs for the photoactivated delivery of metal-based drugs
To the different ligand solubility, oleic acid was exchanged for etidronic acid, alendronic acid or nitrilo(trimethylphosphonic acid) (3P) in a CHCl3 :H2 O mixture (Figure 1b), affording water dispersible nanoparticles where the negatively charged phosphonates are electrostatically tethered to the positive surface of the Gd-UCNPs

Summary

Introduction

Our group developed a number of unconventional approaches for the photoactivation of metal-based anticancer prodrug complexes [1,2,3], including the use of lanthanide-doped upconverting nanoparticles (UCNPs) as near infrared (NIR) light triggers [4,5,6]. In this context, we and others reported on the capacity of UCNPs to prompt the photochemistry of several transition metal complexes such as Ru, Pt, Mn and Fe [7]. We recently demonstrated the functionalization and UCNP loading of photoactivatable

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