​Detecting diseases in their very early stages, particularly cancers, requires highly sensitive and specific diagnostic imaging tools. For this purpose, MRI [1] uses functionalized contrast agents, which are molecules that can target biomarkers of disease. In addition to their efficiency in precisely locating these biomarkers, these agents must be biocompatible and non-toxic. Even though they are the most used agents today in clinical examinations, some gadolinium chelates exhibit high toxicity risks to patients.

A new generation of contrast agents has been created through a multidisciplinary approach combining biologists, chemists and physicists from the CEA-IBEB and CEA-I2BM. It uses magnetotactic bacteria that naturally produce magnetosomes, which are nano-magnets surrounded by a biological membrane that is soluble in aqueous media. “These nano-magnets are non-toxic”, explains Nicolas Ginet, researcher at the CEA-IBEB. “And we have demonstrated that they are highly effective as a contrast agent in a rodent brain tumor model.” Another advantage: their production is simple. “You just need to compress the bacteria and collect the magnetosomes with a magnet”, adds the biologist.

  A magnetotactic bacterium and its magnetosomes. © CEA

How do these nano-magnets precisely reveal the biomarkers to be detected? “By functionalizing them”, says Nicolas Ginet. “In our experiments with rodents, we have ‘attached’ to the nano-magnets a protein [2] capable of identifying the cells of blood vessels that feed the brain tumor.” In the long term, the researchers want to genetically modify the magnetotactic bacteria so as to customize the functionalization of magnetosome surfaces. “A therapeutic tool can be added to the diagnostic tool”, continues the researcher. “You just need to add a therapeutic molecule to the surface of the nano-magnet, which will specifically target the diseased area.

This work is funded by the National Research Agency (ANR) under the MEFISTO project, in the amount of 1.5 million euros.

Compared to a commercial MRI contrast agent (ferumoxide), a very low dose of magnetosomes (magnetite nanocrystals biomineralized by magnetotactic bacteria) can still be detected in the mouse brain with an ultra-high-field MRI scanner (17.2 T). © CEA

[1] Magnetic resonance imagering

[2] This is the RGD peptide, which targets certain integrin receptors overexpressed on the surface of cells in the angiogenic network of the tumor.