They turn a bacterium fluorescent and convert it into a double contrast agent for MRI

by time news

2023-08-11 16:45:33

Scientists have managed to modify certain characteristics of a bacterium known for its magnetic properties and make it a promising clinical diagnostic agent.

By adding metallic elements (terbium or gadolinium) to the culture medium of the bacteria, it integrates them and becomes a fluorescent or dual contrast agent, very useful for magnetic resonance imaging.

The work has been led by the Magnetism and Magnetic Materials group of the University of the Basque Country (UPV/EHU), in Spain.

The aforementioned Magnetism and Magnetic Materials group has been working with magnetotactic bacteria for more than a decade, a group of aquatic bacteria that in their natural environment synthesize magnetite crystals (an iron mineral), which act as compasses and enable these bacteria to Orient and navigate along the Earth’s magnetic field lines.

“The intrinsic functionalities of these bacteria make them very interesting for the clinical field, since they have all the characteristics that are needed to be used as nanorobots. In addition to being able to guide them by means of magnetic fields to the area to be treated, numerous works have demonstrated the potential that magnetotactic bacteria have to be used in different practices, such as magnetic hyperthermia (an anticancer therapy), as drug carriers and as agents of contrast to obtain magnetic resonance images”, explains Lucía Gandarias Albaina, researcher of the aforementioned research group and first author of this study.

However, these bacteria present a difficulty: “They are not easy to modify; they have interesting characteristics intrinsically, but it is not easy to introduce new functionalities”, points out the researcher. One of the strategies followed in this sense is to enrich the culture medium with certain substances, and see the effect that this has on the bacteria.

In collaboration with a research group from the University of Cantabria, in Spain, which is a specialist in rare earths (elements also called lanthanides), and with the participation of other researchers from centers such as CIC biomaGUNE (Spain), HZB (Helmholtz- Zentrum Berlin, Germany) and BIAM-CEA (France), set out to study the effect of adding terbium (Tb) and gadolinium (Gd) to the culture medium of the Magnetospirillum gryphiswaldense bacterium, that is, “how would the potential of this bacterium as a biomedical agent by incorporating these elements”, says Gandarias.

The internalization of terbium and gadolinium by bacteria brought the appearance of new functionalities. This is how the researcher describes it: “In our analyses, we saw, on the one hand, that terbium makes bacteria fluorescent, so they could be used as biomarkers, since it would be possible to track where they are. On the other hand, we verified that, by incorporating gadolinium, the bacteria acquire the character of dual contrast agents for magnetic resonance imaging, which is where research in this field of study is heading.”

Images of the bacterium Magnetospirillum gryphiswaldense (referred to as MSR-1). Left: images obtained with transmission electron microscopy where the chain of magnetosomes inside the bacterium can be seen in detail. Rest of images: X-ray fluorescence microscopy images showing the location of iron (which coincides with the chain of magnetosomes) and terbium/gadolinium (which is distributed throughout the bacterium). These images were obtained on line I14 of the DLS synchrotron (Diamond Light Source, UK). (Images: UPV/EHU / Lucía Gandarias et al., Materials Today Bio, 2023)

MRI requires the person undergoing it to take contrast agents, a class of products that improve imaging differentiation between normal and damaged tissue and facilitate diagnosis. Two types of contrast are currently used: the positive ones, or T1, which are the most widely used and are based on gadolinium compounds, and the negative ones, or T2, which are iron oxide nanoparticles. “Since our bacteria already had iron particles as part of their magnetic particles and are capable of integrating gadolinium from the culture medium, they can function as dual contrast agents,” explains Gandarias. Because the appearance of the new functionalities described has not made the previous ones disappear.

In view of these results, the researcher predicts a very promising future for the use of bacteria in clinical practice: “Although we are at the beginning, work is being done on the use of bacteria for cancer treatments; there are many studies in different phases. In our case, in the in vitro tests carried out we have verified that the bacteria are not toxic to cells, which will allow us to continue studying in this line”.

The study is titled “Incorporation of Tb and Gd improves the diagnostic functionality of magnetotactic bacteria”. And it has been published in the academic journal Materials Today Bio. (Source: UPV/EHU)

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