In vitro and in vivo acute toxicity of a novel citrate-coated magnetite nanoparticle

• Published in: PloS one Vol. 17; no. 11; p. e0277396
• Main Authors: Rocha, Jose Marcos Vieira, de Souza, Valeria Barbosa, Panunto, Patricia Costa, Nicolosi, Jacqueline Spacagna, da Silva, Emanueli do Nascimento, Cadore, Solange, Londono, Oscar Moscoso, Muraca, Diego, Tancredi, Pablo, de Brot, Marina, Nadruz, Wilson, Ruiz, Ana Lucia Tasca Gois, Knobel, Marcelo, Schenka, Andre Almeida
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-11-2022; Public Library of Science (PLoS)
• Subjects: Acute toxicity; Atomic absorption spectroscopy; Biocompatibility; Biology and Life Sciences; Biomedical materials; Cell lines; Cellulose acetate; Citrates; Citric Acid; Coatings; Drug delivery; Drug delivery systems; Drug dosages; Engineering and Technology; Ethics; Ferric Compounds - chemistry; Ferric Compounds - toxicity; Ferrosoferric Oxide; Humans; Hyperthermia; In vivo methods and tests; Iron oxides; Laboratories; Liver; Liver cancer; Magnetic fields; Magnetic resonance; Magnetic Resonance Imaging; Magnetite; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - toxicity; Medicine and Health Sciences; Metabolism; Nanomaterials; Nanoparticles; Nanotechnology; Neuroimaging; Pharmacodynamics; Pharmacokinetics; Pigments; Research and Analysis Methods; Risk assessment; Scientific imaging; Spectral analysis; Spectrometry; Toxicity; Transmission electron microscopy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0277396

Magnetic nanoparticles (MNps) have become powerful tools for multiple biomedical applications such as hyperthermia drivers, magnetic resonance imaging (MRI) vectors, as well as drug-delivery systems. However, their toxic effects on human health have not yet been fully elucidated, especially in view of their great diversity of surface modifications and functionalizations. Citrate-coating of MNps often results in increased hydrophilicity, which may positively impact their performance as drug-delivery systems. Nonetheless, the consequences on the intrinsic toxicity of such MNps are unpredictable. Herein, novel magnetite (Fe3O4) nanoparticles covered with citrate were synthesized and their potential intrinsic acute toxic effects were investigated using in vitro and in vivo models. The proposed synthetic pathway turned out to be simple, quick, inexpensive, and reproducible. Concerning toxicity risk assessment, these citrate-coated iron oxide nanoparticles (IONps) did not affect the in vitro viability of different cell lines (HaCaT and HepG2). Moreover, the in vivo acute dose assay (OECD test guideline #425) showed no alterations in clinical parameters, relevant biochemical variables, or morphological aspects of vital organs (such as brain, liver, lung and kidney). Iron concentrations were slightly increased in the liver, as shown by Graphite Furnace Atomic Absorption Spectrometry and Perls Prussian Blue Staining assays, but this finding was considered non-adverse, given the absence of accompanying functional/clinical repercussions. In conclusion, this study reports on the development of a simple, fast and reproducible method to obtain citrate-coated IONps with promising safety features, which may be used as a drug nanodelivery system in the short run. (263 words).