Moscow, July 1, 2024
Researchers have synthesized tannic acid-coated magnetic beads capable of extracting membrane vesicles called “exosomes”
from biological fluids with 60% efficiency. This novel method will make it easier and faster to isolate exosomes from
laboratory samples, while the chemical composition of the exosomes will help detect cancer in its early stages. The
study supported by a grant from the Presidential Program of the Russian Science Foundation (RSF) was published in the
Journal of Materials Chemistry B.
Cells in the human body “communicate” through exosomes — tiny membrane vesicles that are released into the intercellular
space and carry proteins, fats, nucleic acids, and other molecules. Since the exosomes’ contents replicate the chemical
composition of the cell they split off from, they can be used as molecular markers to identify various diseases. For
example, the presence in exosomes of proteins and RNA typical of cancer cells is compelling evidence of incipient
cancer.
However, exosome-based diagnostics is not yet widely used in clinical practice because these vesicles are as small as
viruses and therefore difficult to isolate. A recently proposed approach uses magnetic beads to capture exosomes from
biological samples, such as blood. The surface of the beads is coated with molecules, such as antibodies, that
specifically bind to exosomes and hold them in place, and the bead-exosome complexes are then extracted from the
biological sample using a magnet. However, this approach has been rather inefficient, prompting researchers to improve
the beads’ ability to bind to exosomes.
A joint team from the Skolkovo Institute of Science and Technology, Lomonosov Moscow State University and the Kulakov
National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health has
improved magnetic beads by applying a layer of tannic acid onto their surface. The researchers synthesized beads of iron
oxide and calcium carbonate (chalk and marble are the most common forms of the latter) and then coated their surface
with a layer of polyvinylpyrrolidone and polyallylaminohydrochloride polymers or albumin, which specifically bind to
exosomes. Finally, the resulting complexes were held in tannic acid which settled on the surface along with the other
molecules.
The researchers placed the magnetic beads in a solution containing a predetermined amount of exosomes to assess the
efficiency of binding, then removed the beads with a magnet and measured the remaining amount of membrane vesicles.Formation of the shell of magnetic microparticles and the principle of their interaction with exosomes. Source: Grishaev
et al. / Journal of Materials Chemistry B, 2024.
They found that the tannic acid-coated beads captured 50% to 60% of the exosomes, depending on the type of the second
molecule in the coating (polymer or albumin). Other samples coated with just polymers or albumin showed an efficiency of
only 34%.
The tannic acid-coated beads performed better because the acid formed hydrogen bonds with fats and proteins on their
surface, acting as an additional anchor for the exosomes. Tannic acid also helps to form whole complexes, with membrane
vesicles adhering to the bead and to each other, allowing more of them to be extracted from the solution.
The exosome capture efficiency achieved by the team is comparable to the quality of the widely used but extremely
cumbersome exclusion chromatography method, in which exosomes are sieved through a layer of gel to separate them from
other components of the liquid. The new approach is also less time-consuming — 2.5 hours versus 4 hours — which will
speed up the entire procedure and enable its wider use in clinical practice.
“In the future, the widespread use of exosome chemical composition analysis will help facilitate the early diagnosis of
various types of cancer. Going forward, we plan to improve the surface structure of the magnetic beads to further
increase their efficiency,” said Alexey Yashchenok, an associate professor at the Skoltech Photonics Center and the head of the RSF-supported
project.
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Note: Skoltech is a private international university in Russia, cultivating a new generation of leaders in technology,
science, and business, conducting research in breakthrough fields, and promoting technological innovation to solve
critical problems that face Russia and the world. Skoltech focuses on six priority areas: life sciences, health, and
agro; telecommunications, photonics, and quantum technologies; artificial intelligence; advanced materials and
engineering; energy efficiency and the energy transition; and advanced studies. Established in 2011 in collaboration
with the Massachusetts Institute of Technology (MIT), Skoltech was listed among the world’s top 100 young universities
by the Nature Index in its both editions (2019, 2021). On Research.com, the Institute ranks as Russian university No. 2
overall and No. 1 for genetics and materials science. In the recent SCImago Institutions Rankings, Skoltech placed first
nationwide for computer science.