"Smart" nanoparticles: self-assembly, diagnosis and treatment of cancer
He finds and heals himself
Alexandra Borisova, "Newspaper.Ru»A unique drug based on nanoparticles, combining the diagnosis and therapy of cancer tumors, was developed by Russian scientists of the Institute of Bioorganic Chemistry.
Multifunctional medicine is able to find tumor cells in the body, selectively connect with them and ensure their destruction under the influence of an external field. While the drug has been tested in vitro, the in vivo stage is next.
The medicine of the future should be "smart" (that is, independently finding a field of activity, diagnosing the disease), directed (to act without side effects) and individual (selected for each patient with his problem and stage of development of the disease). This is especially true of oncological diseases, in which the fight against malignant cells is often accompanied by the oppression of the whole organism and its destruction. Of course, this is still a fantasy in its own way.
However, the prototype of "smart" drugs can be seen already now – in the latest developments of leading scientists.
Employees of the Laboratory of Molecular Immunology of the Institute of Bioorganic Chemistry. Academicians M. M. Shemyakin and Yu. A. Ovchinnikov of the Russian Academy of Sciences were able to create a multifunctional drug based on protein-crosslinked nanoparticles, which is able to independently identify a tumor in the body, stain it, making it visible to a doctor, and then can destroy the affected cells under the influence of an external magnetic field. Their work is published by Proceedings of the National Academy of Sciences.
The team of authors of the work under the leadership of the head of the laboratory, Corresponding member of the Russian Academy of Sciences Sergey Mikhailovich Deev, is generally very young. One of the co–authors is a young candidate of sciences, the other is a graduate student, but the first author of the work, Maxim Nikitin, is now completing the sixth year of his master's degree at MIPT in Dolgoprudny.
Department of Science "Newspapers.Ru" congratulated Maxim on such a serious achievement at the dawn of his scientific career and asked him to tell more about the work carried out.
– What is the novelty of your developments?– Nanotechnological medical preparations are now the "cutting edge" of science.
Different countries are developing different approaches to this issue, there are developments on magnetic, gold nanoparticles, quantum dots, etc. Most of the research is devoted either to the creation of drugs themselves, or technologies for their targeted drug delivery, which will ensure the delivery of the drug directly to the part of the body that needs it.
In principle, quite a lot of drugs based on nanoparticles have been created, all of them have their advantages and disadvantages. In particular, nanoparticles conjugated with antibodies are able to find cancer cells in the body and selectively attach to them. If the particles are fluorescent, then they can be used to diagnose malignant tumors – they specifically stain them. If the particles are magnetic, then they can be used to destroy tumors or metastases – under the influence of an external field, they heat up and kill cancer cells.
The importance and novelty of our work is that we have developed an approach for creating multifunctional agents that combine both magnetic and fluorescent particles and antibodies that "target" the drug to a cancerous tumor. Moreover, this approach is universal, due to it, other functions can be given to this structure, for example, to attach a toxin, virus or bacterium that will kill the target cell.
Thus, the combination of valuable properties of nanoparticles makes it possible to obtain a drug that works sequentially for the diagnosis and then for the treatment of a tumor.
At the first stage, such multifunctional structures could recognize cancer cells due to antibodies, and at the expense of fluorescent quantum dots or polymer particles, color the tumor so that the surgeon could see which area needed to be removed. At the second stage, metastases can be destroyed – the most dangerous manifestation of cancer. To do this, magnetic nanoparticles are used, which are part of the same structures. They destroy the remaining cancer cells under the influence of an external magnetic field.
In fact, the multifunctionality of the drug is achieved by combining different particles in one structure. As in a children's designer, we can combine completely different particles in one medicine.
How do these particles combine? To do this, we use two special bacterial proteins that interact strongly with each other – barnase and barstar. One type of particle is conjugated with one protein, another type with another. After mixing such bioconjugates, they bind firmly, due to which agents completely different in size and chemical nature can be combined in one structure.
Our work, like most of the promising research today, is conducted at the intersection of sciences – in fact, it is both physics and biology.
– How was the drug tested?– At the first stage of the study, we developed a mechanism for self-assembly of particles, and ensuring successful assembly was our intermediate goal.
At this stage, we were not talking about therapy yet, but only about the successful development of a mechanism, a matrix for the combination of different particles in one drug.
At the second stage, in vitro tests of our particles on cell cultures began. It turned out that our mechanism works very successfully.
Three functional structures were added to cancer cells: magnetic, fluorescent and antitumor (directed at cancer cells by antibodies). At the first stage, the particles successfully joined the receptors, specifically distinguishing the target cells from other cells.
Then we applied a tricky magnetic field to the suspension of such "labeled" cells so that the cells linked to the nanoparticles formed the letters MF (English – multifunctional, multifunctional). As can be seen in the illustration, the cells have successfully positioned themselves along this contour (the scale size is 0.5 mm). This elegant example shows how we can control the movement of cells linked to nanoparticles. Thus, for example, it is possible to remove cancer cells from the blood of a leukemia patient with a magnetic field. After we examined the sample with a fluorescent microscope, the letters "lined" with cells glowed. This means that the fluorescent component of the trifunctional structures also works, successfully "coloring" cancer cells.
This is a very convenient technique for the development of individual drugs – we see it as a kind of "medicine of the future".
– How will the work of such a drug be practically implemented?– In the future, it will be possible to choose a separate treatment and its own medicine for each patient with the necessary ratio of structural units in it.
Depending on the specific situation, the doctor can decide what should be given more attention, for example, diagnosis or therapy, in the case of this particular patient. Accordingly, in a matter of minutes, the doctor will be able to combine the necessary modules into multifunctional structures, using preparations from 20 jars standing on the table.
The practical use of such drugs for treatment is still a distant plan. However, studies of the obtained multifunctional drugs in vivo are already underway – we check whether they are suitable for the diagnosis and treatment of tumors in mice and rats, and also look at what happens to nanoparticles in living organisms.
– How was the preparation for the publication of the received data conducted?– Our publication was preceded by a lot of work.
Suffice it to say that during the discussion there were 27 variants of the manuscript, in total more than 180 variants of drawings were prepared. Only five were included in the article (five more in the extended application of the work). The work was supported by the RAS programs "Molecular and Cellular Biology", "Nanotechnology and Nanomaterials", as well as the Russian Foundation for Basic Research.
Portal "Eternal youth" http://vechnayamolodost.ru16.03.2010