Danger cubed: scientists have found that the shape of nanoparticles affects their toxicity to the liver

Scientists from NUST MISIS, Baltic Federal University, D. Mendeleev University of Chemical Technology of Russia and the Czech Academy of Sciences have found that iron oxide nanoparticles of a certain size and shape, often used in biomedicine, cause autophagy and death of liver cells due to the destruction of lysosome membranes. Such nanoparticles in general can be highly toxic to people with liver disease. The results of the study have been published in the Nano Convergence international scientific journal.

Iron oxide nanoparticles are now increasingly used for targeted drug delivery in the treatment of cancer and as contrast agents for magnetic resonance imaging for the examination and visualization of liver diseases.

Initial studies of the cytotoxicity (harm to body cells) of such nanoparticles have shown that they are highly biocompatible and well tolerated by the body. As a result, iron oxide nanoparticles have been approved for medical use. However, over time, more and more evidence of the toxicity of such nanoparticles has appeared in clinical practice. Their interaction with various types of cells, in particular, hepatocytes (liver cells) remains poorly understood, which means that nanoparticle-based preparations can be dangerous to the health of patients.

Scientists from the international research team from Russia and the Czech Republic have studied the effect of high concentrations of cubic iron oxide nanoparticles and their clusters on human liver cells, since it is this form of particles that shows excellent results in MRI studies. Researchers have experimentally found that hepatocyte viability, in fact, decreased depending on the increase in the concentration of cubic nanoparticles in the organ.

"In this work, we demonstrate that the effect of nano-cubes and their clusters leads to cytotoxicity in various tumor cell lines of the liver. The mechanism of the toxic effect is associated with the progressive permeability of lysosome membranes in hepatocytes. It provokes the processes of apoptosis and autophagy — cell death, — said one of the co-authors of the study, head of the NUST MISIS Biomedical Nanomaterials Laboratory Maxim Abakumov.

As the authors of the study emphasize, that hepatotoxicity — the negative effect of substances on liver cells — is one of the most common reasons for the withdrawal of drugs from the market (~ 30% of such cases).

Previously, the developers have shown that it is possible to avoid the capture of nanoparticles by liver cells by using special formations — nano-clusters. Thus, when using cubic iron oxide nanoparticles for medical purposes, the dosage of drugs based on them must be strictly observed.