In Vivo Pharmacokinetics, Biodistribution and Toxicity of Antibody-Conjugated Gold Nanoparticles in Healthy Mice

Noami Daems, Bart Verlinden, Karen Van Hoecke, Thomas Cardinaels, Sarah Baatout, Carine Michiels, Stéphane Lucas, An Aerts

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

Cetuximab-conjugated gold nanoparticles are known to target cancer cells, but display toxicity towards normal kidney, liver and endothelial cells in vitro. In this study, we investigated their pharmacokinetics, biodistribution and toxicity after intravenous administration in healthy mice. Our data showed that these nanoparticles were rapidly cleared from the blood and accumulated mainly in the liver and spleen with long-term retention. Acute liver injury, inflammatory activity and vascular damage were transient and negligible, as confirmed by the liver functionality tests and serum marker analysis. There was no sign of altered liver, kidney, lung and spleen morphology up to 4 weeks post-injection. After 6 months, kidney casts and splenic apoptosis appeared to be more prevalent than in the controls. Furthermore, occasional immune cell infiltration was observed in the lungs. Therefore, we recommend additional in vivo studies, in order to investigate the long-term toxicity and elimination of gold nanoparticles after multiple dosing in their preclinical validation as new targeted anti-cancer therapies.

langue originaleAnglais
Pages (de - à)985-996
Nombre de pages12
journalJournal of Biomedical Nanotechnology
Volume16
Numéro de publication6
Les DOIs
Etat de la publicationPublié - 1 juin 2020

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