Synthesis and in vivo evaluation of PEG-BP–BaYbF5 nanoparticles for computed tomography imaging and their toxicity
| Autor: | Xianjin Cui, Vicky Goh, Rafael Torres Martin de Rosales, Lea Ann Dailey, Jaclyn L Lange, Cinzia Imberti, Thais Fedatto Abelha, Yong Yan, Istvan Szanda |
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| Rok vydání: | 2020 |
| Předmět: |
Biomedical Engineering
Nanoparticle Biocompatible Materials Chemistry Techniques Synthetic 02 engineering and technology 010402 general chemistry 01 natural sciences Polyethylene Glycols Nanomaterials In vivo Cell Line Tumor PEG ratio medicine Humans General Materials Science Diphosphonates medicine.diagnostic_test Chemistry General Chemistry General Medicine 021001 nanoscience & nanotechnology In vitro 3. Good health 0104 chemical sciences Toxicity Angiography Nanoparticles Tomography Tomography X-Ray Computed 0210 nano-technology Biomedical engineering |
| Zdroj: | Journal of Materials Chemistry. B |
| ISSN: | 2050-7518 2050-750X |
| DOI: | 10.1039/d0tb00969e |
| Popis: | 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 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 using TEM, DLS, TGA, XRD and Z-potential measurements. Their in vitro stability 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 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 the promising CT contrast properties, our results suggest that BaYbF5 nanomaterials may suffer from significant long-term toxicities. PEG(5)-BP–BaYbF5 nanoparticles provide superior CT contrast and circulation time compared to clinically-used iodinated molecules, but suffer from unexpected in vivo toxicity. |
| Databáze: | OpenAIRE |
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