The fate of the nanoparticle
Biochemists have studied the aging and destruction of magnetic nanoparticles in the body
Phys Tech blog, Naked Science
A group of scientists from IBH RAS, MIPT, Sirius University, IOF RAS, NRU MEPhI and RNIMU were the first to investigate the long-term fate of magnetic nanoparticles in animals. They are used for targeted drug delivery and are already approved for use in medicine. But for a long time it was unknown what happens to nanoparticles after they carry out therapy. Thanks to the new development of Russian biochemists, it became known how magnetic nanoparticles "age" and decay in the mammalian body.
The results are published in the highly rated journal ACS Nano (Zelepukin et al., Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study). Targeted drug delivery is one of the breakthrough directions in the development of modern diagnostics and therapy of various diseases. Ideally, "smart" nanoparticles transporting drugs should themselves find, recognize and treat the focus of the disease. Magnetic nanoparticles are a common object of scientific research in the field of targeted therapy, they are widely used for controlled drug delivery and are already used in medical practice.
In particular, they are bright, contrasting agents for magnetic resonance imaging (MRI) — one of the most popular functional diagnostic tools today. In addition, a number of compositions of magnetic particles with sugars are used for the treatment of iron deficiency anemia. For a long time it remained unclear how nanoparticles behave in the body after they have fulfilled their function.
A team of Russian biochemists has developed a new spectral magnetic method for detecting materials. It allows you to separate the signal of magnetic nanoparticles from iron, which is normally contained in the body. The mouse is located in the liver and spleen area above the magnetic coil acting on the nanoparticles and the magnetic response measures how much iron remains in the particles and which has already entered the mammalian proteins.
Scheme for measuring the aging of magnetic particles in the liver and spleen of mammals / ©ACS Nano.
The high sensitivity of the method and the ability to carry out measurements without the death of animals made it possible for the first time to conduct such a large-scale research in the field of nanobiotechnology. Scientists were able to compare the degradation rate of 17 types of nanoparticles, studied the effect on the biodegradation in the body of their size, dose, surface charge, coating and internal structure. After introduction into the bloodstream, nanoparticles accumulate in lysosomes and slowly dissolve under the action of acid and enzymes.
Scientists have shown that the speed of this process depends very much on the internal structure of the material and with the help of the design of nanoparticles, it is possible to accelerate the time of complete degradation from several years to one month. For example, small particles with a negative charge degraded the fastest. Among the various polymers covering the particles, glucuronic acid polymer slowed down the dissolution the weakest, and polystyrene was the strongest.
"This work would not have been possible without creating an approach for noninvasive detection of magnetic particles in the body. The measurements were carried out for more than a year. Using classical approaches would require more than a thousand mice for such an experiment, which is unreasonable both for ethical reasons and for financial and human labor costs," notes Maxim Nikitin, one of the authors of the article, head of the Laboratory of Nanobiotechnology at MIPT, head of the Nanobiomedicine department at Sirius University of Science and Technology.
Then the scientists tried to understand what happens to the remnants of nanoparticles. They found that excess iron, which was formed when they dissolved, is not excreted from the body. Instead, the animals decreased the absorption of the iron that comes from food. As a result, iron from the particles completely passed into low-toxic forms, was deposited in the liver and spleen and was probably used by the body at its discretion: to create red blood cells, regulate metabolic processes and other applications.
An important discovery was the absence of long-term toxicity of magnetic particles for the body. The only changes that were detected were a temporary increase in the population of immune cells involved in particle recognition and processing, as well as a long-term deposition of excess iron in the liver and spleen.
"The fact that magnetic particles pass into biogenic iron is an important feature. It can be used for the therapy of some forms of anemia, – says Ivan Zelepukin, the first author of the article, a junior researcher at the Laboratory of Molecular Immunology of the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, a graduate of MIPT – Our research sheds light on a reasonable design of nanomaterials with a controlled rate of iron release."
The study was carried out with the support of the Russian Science Foundation and the Russian Foundation for Basic Research and is a continuation of a series of works that study the mechanisms of interaction of particles with the body. You can read about the group's previous research on the website of the MIPT journal "For Science".
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