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Technion researchers have developed new nanometer particles to mark cells for MRI imaging and light microscopy

The new technology will help in mapping nerve cells in the brain and identifying cancer cells

In the figure: the bimodal particle consists of a hollow sphere of iron oxide (in gray) inside which floats a light-emitting particle (in red)
In the figure: the bimodal particle consists of a hollow sphere of iron oxide (in gray) inside which floats a light-emitting particle (in red)

An interdisciplinary research team from the Technion has developed nanoscale particles that will improve the quality of brain scans. This is by combining MRI scanning and light microscopy photography. The researchers, all members of the Russell Berry Nanotechnology Institute (RBNI), are Prof. Lilach Amirav from the Shulich Faculty of Chemistry, Dr. Shai Berlin and Prof. Itamar Kahn from the Rapaport Faculty of Medicine. A central role in the work was played by Dr. Sandeep Fehri and Shonit Olshekar, a doctoral student in Dr. Berlin's laboratory.

Scanning biological tissues in MRI (Magnetic Resonance Imaging) is a non-invasive technology that has revolutionized the world of medicine, as it presents an extensive and deep image of tissues, organs and even the entire body. Its disadvantage is that it does not provide high resolution at the single cell level. Light microscopy, on the other hand, is able to provide a high level of separation, at the level of individual cells, but it requires penetration into the tissue.

Against this background, research teams around the world are working on developing a technology that will combine the MRI with the light microscopy, so that the resulting product will be a wide image with high resolution. In a brain scan, for example, the microscope will allow mapping of individual cells, while the MRI will provide the image of the entire brain. An effective combination of the two technologies, called in vivo dual-modal imaging, will give researchers and doctors the best of both worlds.

This combination is a very complex technological challenge, so its solution requires interdisciplinary cooperation that combines capabilities in many fields, including chemistry, molecular and cellular biology, MRI physics and medical sciences - a collaboration recently achieved in the Technion research team. According to Prof. Amirav, "the main challenge was the development and production of particles capable of being used as bimodal markers, meaning particles that 'color' cells with a signal that can be seen using an MRI machine and a light microscope at the same time." According to Prof. Amirav, solutions previously tested in the world included attempts to connect particles of the iron oxide type, which can be simulated in an MRI, to light-emitting materials that can be seen in the optical microscope. The problem is that direct connection of the two materials to each other results in the loss of light emission and thus neutralizes the marker for the light microscope. A recently introduced alternative solution involved a multiparticle binder (both MRI and light microscopy markers). Despite some success in realizing this design, the size of the binder increases its toxicity, limits its introduction into various biological tissues and may greatly affect the duration of its stay in the tissue or cell (ie the time in which the imaging can be performed).

In two recently published articles, the Technion research team summarizes its success in developing nanometric particles that serve as effective bimodal markers that meet the aforementioned need. The size of each particle is about 10 nanometers and it consists of a hollow sphere of iron oxide inside which floats a light-emitting particle. This structure, reminiscent of an egg, with a hollow shell and a core inside, prevents direct contact between the various materials and thus allows the properties of each of the components to be maintained, and in particular preserves the light emission that is essential for imaging in the optical microscope.

In the first article, published in the journal Chemistry of Materials, Prof. Amirav and Prof. Kahn presented the tiny particle and its biological applicability. Now, following Dr. Berlin's joining the research, the biological component has been added to the particle. In the current article, published in the journal Frontiers in Neuroscience, the three present bimodal imaging in living cells and the experimental progress achieved in recent months.

"After the successful development of tiny bimodal particles, i.e. particles readable by MRI and light microscopy, we added a biological identity to them," explains Dr. Berlin. "This is by coating the particles with a biological shell that allows their introduction into the cell. In other words, we have created entities that know how to navigate into cells, and in the future we will be able to adjust the shell to allow you to mark specific cells. The bimodal particles we created are visible in an optical microscope and in an MRI, and their tiny size gives them another notable advantage: they know how to penetrate target cells and accumulate in them, a feature that allows us to selectively scan them in an MRI and an optical microscope for an extended period of time."

The research, the researchers note, is still in progress. The current articles present proof of feasibility regarding the function of the particles, their biological compatibility and their ability to penetrate cells, especially cancer and nerve cells. The research groups continue to work on the design and development of new and sophisticated multi-purpose particles and the methods of introducing them into cells in a targeted and selective manner. According to Dr. Berlin, "In order to mark the target cells so that our particles will navigate to them, we are developing innovative ways to mark selected cells with engineered viruses, so that in those cells the viral infection will lead to the expression of an 'antenna protein' that will attract and absorb the particles and allow prolonged and specific imaging."

Although the potential range of application is vast, the joint research team is primarily interested in the brain. "In the brain," explains Prof. Kahn, "there are billions of cells of different types: excitatory cells, suppressive cells and support cells. That is why our ability to differentiate between different cell populations is important. For this, it is essential to distinctly mark cells associated with some neurodegenerative disease, for example Parkinson's. The multifunctional particles we have developed will make this possible. We will mark the specific cell population, send our particles to them and follow them over time using our dual monitoring in MRI and microscopy."

The new technology may also help identify cancer cells and treat them. "If we make the cancer cells express the same antenna protein," says Dr. Berlin, "our particles will accumulate in them and thus we can precisely identify the location of the cancer cells in an MRI scan and attack them precisely."

The research was conducted within the framework of the Russell Berry Nanotechnology Institute (RBNI) and the Lori Lockey Interdisciplinary Center for Life Sciences and Engineering, and was funded by the National Science Foundation (ISF), the American Institutes of Health (NIH), the Adelis Foundation and the Prince Center for the Study of Degenerative Diseases neural.

For the full article in Frontiers in Neuroscience

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