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 the Moscow Institute of Physics and Technology, has developed a new non-invasive method for monitoring nanoparticles in the bloodstream, which has a high temporal resolution. The method made it possible to establish the main regularities that affect the life of particles in the bloodstream and seem promising for the development of more effective nanoagents for biomedical applications.
The results are published in the Journal of Controlled Release. Clinical applications of any nanoparticles require an accurate analysis of their behavior in the body, especially the residence time of nanoparticles in the bloodstream. It is this parameter that determines whether the nanoparticles will have time to spread throughout the body, reach their therapeutic target (for example, a tumor), and contact it. In addition, an unnecessarily long 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 is studied today mainly using various methods of taking blood samples and analyzing the content of nanoagents in it. “The problem with such methods is that often particles are 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 analysis”, comments Maxim Nikitin, co-author of the article, head of the laboratory nanobiotechnology MIPT.
In addition, the very procedure of sequential blood sampling brings stress to the body and can indirectly affect the circulation of nanoparticles. New non-invasive methods of tracking the fate of nanoparticles in the body are in great demand for the development of nanomedicine.
The authors of the work – scientists from the Moscow Institute of Physics and Technology, 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, the Moscow Engineering Physics Institute and the Sirius University – applied the previously developed inductive magnetic particle quantification method (MPQ – from English magnetic particle quantification) for non-invasive measurements of particle dynamics in blood.
To do this, they placed the tail of animals, mice or rabbits, into the magnetic coil of the device, then injected particles into the blood and monitored 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 at the fingertips.
Studies have shown that the method used makes it possible to non-invasively register the kinetics of particles in the bloodstream, unique in terms of information content, and much easier than classical approaches. This allowed a detailed study of what could influence the behavior of particles in the bloodstream of animals. The researchers studied three groups of factors: the properties of the particles, the peculiarities of their introduction, and 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 with therapeutic nanoparticles, for example, liposomes with drugs. We have shown that particles can influence each other, and this can 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 introduced. 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 faster, 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 during the development of pathology. Usually, such information about the state of the body was previously ignored 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.