Excretable, ultrasmall hexagonal NaGdF₄:Yb50% nanoparticles for bimodal imaging and radiosensitization

Background: In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF₄:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly. Results: Our ultrasmall β-NaGdF₄:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF₄:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF₄:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd³⁺ ions via ICP-MS. Conclusion: These biocompatible and in vivo clearable ultrasmall NaGdF₄:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.