Synthesis and in vivo Evaluation of PEG-BP-BaYbF5 Nanoparticles for Computed Tomography Imaging and their Toxicity

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Abstract

Computed tomography (CT) is one of the most widespread imaging techniques in clinical use worldwide. CT contrast agents are administered to improve soft tissue contrast and highlight blood vessels. However, the range of CT contrast agents available in the clinic is limited and they suffer from short-circulation times and low k-edge values that result in the need for high doses forin vivoapplications. Nanomaterials containing a mixture of electron-dense elements, such as BaYbF 5nanoparticles, have shown promise as more efficient CT contrast agents, but they require biocompatible coatings for biomedical applications. Here, we explore the use of a bifunctional PEG polymer (5 kDa) containing a terminal bisphosphonate (BP) anchor for efficient binding to the surface of BaYbF 5nanomaterials. The resulting PEG(5)-BP-BaYbF 5nanoparticles were synthesized and characterized using TEM, DLS, TGA, XRD andZ-potential measurements. Theirin vitrostability was verified and their ability to produce CT contrast in a wide range of X-ray energies, covering preclinical and clinical scanners, was demonstrated.In vitrotoxicity studies with PEG(5)-BP-BaYbF 5in the phagocytic pro-monocytic human cell line U937 did not identify toxic effects, even at high concentrations (30 mM).In vivo, PEG(5)-BP-BaYbF 5exhibited efficient CT contrast for angiography imaging, highlighting blood vessels and vascular organs, and long circulation times as expected from the PEG coating. However, at late time points (48 h),in vivotoxicity was observed. While the causes could not be completely elucidated,in vitrostudies suggest that decomposition and release of Yb 3+and/or Ba 2+metal ions after decomposition of PEG(5)-BP-BaYbF 5may play a role. Overall, despite the promising CT contrast properties, our results suggest that BaYbF 5nanomaterials may suffer from significant long-term toxicities.

Original languageEnglish
Pages (from-to)7723-7732
Number of pages10
JournalJournal of Materials Chemistry B
Volume8
Issue number34
DOIs
Publication statusPublished - 14 Sept 2020

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