Comparative acute intravenous toxicity study of triple polymer-layered magnetic nanoparticles with bare magnetic nanoparticles in Swiss albino mice

Abstract

Iron-oxide nanoparticles are one of the most commercialized nanomaterials and have gained widespread acceptance in nanotherapeutics due to their ability for targeted drug delivery, bioimaging, and various other preclinical and clinical theranostic biomedical applications. However, the absence of regulations, guidelines, and harmonized standards as well as limitations associated with their use in clinical settings in the context of their safety and toxicity profiling necessitates in-depth understanding of their toxicological paradigms. Here we examine the toxicity of modified superparamagnetic iron oxide nanoparticles in Swiss albino mice in terms of body weight changes, organ coefficients, generalized and organ-specific biochemical, and various histological staining parameters after administration of bare (uncoated) magnetic nanoparticles (MNPs) and triple polymer-coated magnetic nanoparticles (MNP-AC-G2-pPEG). Both types of nanoparticles were administered intravenously, in three doses (5, 10, and 25 mg/kg body weight) and results of biochemical and histopathological assessment revealed that the highest dose of bare (uncoated) MNPs significantly altered biochemical and histoarchitectural aspects in vital organs, while coated NPs (MNP-AC-G2-pPEG) was found safe in almost all doses. Furthermore, results of toluidine blue (for mast cells) and Prussian blue (for iron deposition) staining also established that the highest dose administration of bare MNPs in animals significantly enhanced mast cell infiltration and iron deposition in tissue sections of most vital organs, while coated NPs did not demonstrate any such adverse effects. Overall, outcomes of this study aid in establishing that administration of uncoated (bare) magnetic NPs in vivo results in structural and functional toxicological modifications while the coating of these NPs with biocompatible and biodegradable polymers can significantly bring down the toxicity of these NPs.

Keywords:

• Acute toxicity
• in vivo toxicity
• iron-oxide nanoparticles
• triple polymer coating
• biocompatibility

Acknowledgements

This work is supported by the Department of Science and Technology (DST), SERB with grant No. CRG/2019/004018. Akshay Vyawahare is thankful to Institute of Nano Science and Technology, Mohali for providing Junior Research Fellowship. Ajay Kumar is thankful to Indian Council of Medical Research (ICMR) for providing Senior Research Fellowship (No. 45/6/2019-Nan/BMS). Anas Ahmad and Rakesh Kumar Mishra are thankful to Institute of Nano Science and Technology, Mohali for providing Senior Research Fellowship.

Disclosure statement

The authors declare no conflict of interest.