Following the traces of nanoparticles
The behavior of nanoparticles in the body was tracked
Phys Tech blog, Naked Science
Nanoparticles are actively used in medicine for diagnostics as contrast agents, as well as for the treatment of various diseases. However, the development of many new multifunctional nanoagents is hindered by the difficulty of monitoring their fate in the body. A collaboration of scientists, which included specialists from MIPT, has developed a new non-invasive method for monitoring nanoparticles in the bloodstream, which has a high time resolution. The method allowed us to establish the main patterns that affect the life of particles in the bloodstream and appear promising for the development of more effective nanoagents for biomedical applications.
The results are published in the Journal of Controlled Release (Zelepukin et al., Fast processes of nanoparticle blood clearance: Comprehensive study). Clinical applications of any nanoparticles require an accurate analysis of their behavior in the body, especially the time spent by nanoparticles in the bloodstream. It is this parameter that determines whether nanoparticles will have time to spread through the body, get to their target (for example, a tumor) and contact it. In addition, excessive circulation time can be harmful, as it can lead to the accumulation of particles in healthy tissues and, accordingly, increase their side toxicity.
The circulation of nanoparticles in the bloodstream today is studied mainly using various methods of blood sampling and analysis of the content of nanoagents in it. "The problem with such methods is that particles are often removed from the bloodstream very quickly, sometimes even in a few minutes, and the researcher has time to take only 2-3 blood samples, which is not enough for a full–fledged analysis," comments Maxim Nikitin, co-author of the article, head of the laboratory of nanobiotechnology at MIPT.
In addition, the procedure of sequential blood collection itself brings stress to the body and can indirectly affect the circulation of nanoparticles. New noninvasive methods of tracking the fate of nanoparticles in the body are extremely in demand for the development of nanomedicine.
The authors of the work – scientists from MIPT, the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, the A. M. Prokhorov Institute of General Physics of the Russian Academy of Sciences, MEPhI and Sirius University – applied the induction method of magnetic particle detection (MPQ – from the English magnetic particle quantification) developed by them for non-invasive measurement of particle dynamics in blood.
The scheme of conducting experiments. The tail of the mouse was placed in a coil, particles circulating through the vessels of the tail were detected by a magnetic coil in real time / ©Journal of Controlled Release.
To do this, they placed the tail of animals, mice or rabbits, in a magnetic coil of the device, then injected particles into the blood and observed their concentration in the tail veins and arteries in real time. Similar measurements can be carried out on a person, for example, by measuring particles with a magnetic coil in the hand or on the fingertips.
Studies have shown that the method used makes it possible to noninvasively register the kinetics of particles in the bloodstream that are unique in terms of information content, and much easier than classical approaches. This allowed us to study in detail what can affect the behavior of particles in the bloodstream of animals. The researchers studied three groups of factors: the properties of the particles, the features of their introduction, as well as the state of the animal's body.
Small negatively charged nanoparticles injected in high doses stayed in the bloodstream longer. In addition, it was found that if particles are injected into the blood several times in a row, the circulation of subsequent doses of particles is significantly prolonged.
"Similar situations can occur in clinical practice, when a person is first injected with nanoagents that increase MRI contrast (magnetic particles), and then therapeutic nanoparticles, for example, liposomes with medication. We have shown that particles can influence each other, and this may be important in therapy," comments Ivan Zelepukin, the first author of the article and a junior researcher at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences and MIPT.
An extremely important aspect turned out to be the state of the organism into which the particles are injected. Thus, the circulation in mice of different genetic lines could differ several times, and the difference was observed only for small 50-nm particles, and not for larger nanoagents. In addition, if the animal had a developed tumor, the nanoparticles began to be removed from the blood faster, and the sooner the larger the volume of the cancerous tumor.
These facts in the work are associated with dynamic changes in the immune system and its greater ability to recognize foreign substances in the development of pathology. Usually, such information about the state of the body was ignored earlier in experiments, therefore, with their results, the authors draw attention to the need to open this Pandora's box for the optimal design of nanodrugs.
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