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

Research output: Contribution to journalArticle

Original languageEnglish
JournalJournal of Materials Chemistry B
DOIs
Publication statusPublished - 11 Jul 2020

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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 suffer from short-circulation times and low k-edge values that result in the need for high doses for in vivo applications. Nanomaterials containing a mixture of electron-dense elements, such as BaYbF5 nanoparticles, 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 BaYbF5 nanomaterials. The resulting PEG(5)-BP-BaYbF5 nanoparticles were synthesized and characterized by TEM, DLS, TGA, XRD and z-potential measurements. Their in vitro stability was verified and their ability to produce CT contrast at a wide range of X-ray energies, covering preclinical and clinical scanners, demonstrated. In vitro toxicity studies with PEG(5)-BP-BaYbF5 in the phagocytic pro-monocytic human cell line U937, did not identify toxic effects, even at high concentrations (30 mM). In vivo, PEG(5)-BP-BaYbF5 exhibited 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 vivo toxicity was observed. While the causes could not be completely elucidated, in vitro studies suggest that decomposition and release of Yb3+ and/or Ba2+ metal ions after decomposition of PEG(5)-BP-BaYbF5 may play a role. Overall, despite promising CT contrast properties, our results suggest that BaYbF5 nanomaterials may suffer from significant long-term toxicities.

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