Nanomedicine: Hurdling
"Our task is to cross the barrier between the laboratory and the production technology"
Andrey Nikiforov, Post-science
In our project "Where is high-tech business born?" scientists in their laboratories talk about promising research, development and their technological application in various business areas. In this issue, we talked with Natalia Klyachko, Doctor of Chemical Sciences, Professor of the Chemical Faculty of Lomonosov Moscow State University.
The laboratory "Chemical Design of Bionanomaterials" was established in November 2010. The tasks of the laboratory and the directions of its work are united by one – it is molecular modeling and molecular design of bionanomaterials for medical applications.
About nanozymesMaterials and their applications are different, so there are many directions in the work.
Some of these areas existed before the creation of the laboratory, but developed somewhat in other directions. When Alexander Kabanov, the head of the laboratory, came, he combined our research with nanosim – a unique container for biomolecules, with which they can be delivered to various organs, in particular, for medical applications.
The directions of the laboratory's work are connected, on the one hand, with specific diseases, and, on the other, with various design developments. One of the directions is associated with specific enzymes that are capable of destroying very strong poisons – organophosphorus compounds, including military poisons. (An enzyme is a protein that catalyzes, accelerates any reactions in our body.)
This is just the development of our Department of Chemical Enzymology, which deals with enzymes (biological catalysts) in various fields. And one of them is an enzyme catalyst–an antidote, or a preventive agent for poisoning with organophosphorus compounds.
Since the enzyme is isolated from bacteria, it was impossible to use it on humans. He worked wonderfully, destroyed organophosphorus compounds, including such as Vi-Ex, sarin, soman and pesticides. And it turned out that in addition to this enzyme, the technology of creating nanosime developed in the laboratory is very convenient, when it is possible to make such a complex or such a container for the enzyme in a simple way, using multicharged polymers, and actually hide it from the body. And now this enzyme can be used in animals and humans, it becomes non-toxic, non-immunogenic, and, moreover, it is still very active.
Experiments here have already progressed very far. In fact, we have a ready-made product that can be put into practice. Experiments have already been conducted on animals. For example, on rats. In the presence of this enzyme catalyst, the lethal dose, which led to the death of animals, shifted almost three times, that is, three LD100, not even LD50, this is a very big difference.
This means that small concentrations can be injected into the body, which will not be dangerous for humans, and since this enzyme is in the shell, due to this it can function for quite a long time. It turns out that you can use it as a preventive agent before getting into an environment where there are pesticides.
About the delivery of drugs to the bodyThe second area of work is also related to technology ready for use.
There are two branches here. The first is the technology of creating nanoparticles of the antioxidant enzyme superoxide dismutase, which is able to fight oxygen radicals that occur in various inflammatory diseases in our body. Creating a shell for this enzyme allows it to work much better and longer in the body and effectively fight oxygen radicals that occur in inflammatory diseases.
We tested this in ophthalmology on rabbits, to which the enzyme was injected drip. Good results were obtained in immunogenic uveitis, a disease that causes quite significant complications, and in many cases blindness. Using our technology, it was possible to significantly improve the course of the disease and achieve the recovery of animals.
The second branch is associated with the appearance of radical particles as a result of spinal cord injury. We are conducting these studies together with the Serbian Institute. We have developed a model of spinal cord injury so that we can reliably monitor the course of the process. And here we injected the nanocontainer with the enzyme already intravenously. This enzyme significantly facilitates the course of the disease and makes it possible to improve the functional characteristics of animals if they stop moving during injury. Due to the added nanosime, recovery is much faster.
Another area of research in which we have just started is related to metal nanoparticles and the influence of external influences, namely the magnetic field, on various biochemical reactions and various biomolecules. Now these are more fundamental developments, but they also have a practical application. This is the possibility of external influence or purposeful actualization of various processes occurring in the body associated with the targeted delivery of drugs to the body.
If we consider the well-known liposomes that deliver drugs to the body, it often turns out that the medicine is sitting in them and does not go where it is needed. Therefore, the question arises: how to open the lid, how to release the medicine?
And here the idea came up to use a magnetic field, and a low-frequency or ultra-low-frequency, non-warming one. And all the effects are associated precisely with the nanomechanical effect on protein molecules or particles with ligands and the drug.
About Cancer treatmentWe set new goals all the time.
Now we have joined the work on the Skolkovo – Skoltech project, where completely new drugs based not on proteins, but on RNA are being developed. This is the delivery of drugs to tumor cells. Here, developments are being carried out almost from scratch. We have two targeted areas – liver cancer and prostate cancer. But it is quite possible that we will develop further. We are thinking about the lungs and some other organs.
In addition, in the laboratory, individual groups are still working with other grants and projects. For example, with Natalia Nukolova's group. She studied PhD with Alexander Kabanov in the United States, and now works at the Serbian Institute. She deals with containers-nanogels, with the help of which delivery to the brain is carried out. This is a very difficult task. A brain tumor is a huge problem because it develops very quickly and it is almost impossible to remove it. Therefore, the creation of such a drug is a serious challenge.
Such drugs have not yet reached mass production, but we already have two drugs that are almost ready for use. We will now conduct preclinical tests on one of them, an application has already been submitted to the Ministry of Industry and Trade, and we are trying to test the other in a slightly different format. That is, the drug is ready, but there is no commercial use yet.
A small amount of funding comes to us from the university. But since the mega-grant has already ended, this year we did not have all the funding from the ministry. There are a few more grants from the RNF and a number of other organizations that we are still using. Cooperation with commercial companies is a matter of the near future.
Commercial prospects are connected with the fact that many of our drugs are intended for socially significant diseases. They are important precisely from the point of view of commercialization. And I hope that we will have partners who will be able to promote this together with us in the future.
About socially significant drugsAt the moment we have an antidote and a preventive agent against organophosphates and pesticides.
This is very important for agriculture, for people working in agriculture, and for people who accidentally get into the subway, for example, where a leak or deliberate spraying of some substance may occur.
The second drug is an antioxidant nanozyme, which can be used for a very wide range of diseases as an anti–inflammatory agent.
We also have socially significant antisalmonel and antistaphylococcal drugs on our hands. Staphylococcal infection, for example, is dangerous for maternity hospitals and hospitals.
We see a great future in magnetic developments – both in terms of creating an instrument base, and in terms of actual developments. For these purposes, a company was created not so long ago, to which we all belong – Professor Golovin, myself, Alexander Viktorovich Kabanov, and Marina Sokolskaya.
There are many tasks here. These are drugs remotely controlled by external influence, when we load the medicine into a particle, and send the particle into the body and then act with a magnetic field from above. As a result, this particle does what we need. In fact, with the help of a magnetic field, we can either disorder the membrane and allow the enzyme to penetrate into the necessary areas, or help the drug get out of the container, from which it cannot get out on its own. If we need to stop some kind of reaction, then we can start this enzyme and destroy the bonds that it has inside with a field, and the reaction will stop. There are many variants of exposure, and all of them are associated with mechanical action on protein macromolecules through magnetic particles.
The results related to the reactions of the enzyme to the start of the magnetic field are obtained, as a result of which it is possible to control its activity: to make it less or more. The results on the release of the enzyme from the particle were also obtained. This is the same as the drug leaving the particle, when under the action of the field, the particle shakes off the enzyme, if it is not sewn covalently, into the solution. And in this way we can separate from it when it is necessary.
In addition, we synthesized a large number of particles of various sizes and morphologies. These are balls of 8 nm, 20 nm and 50 nm in size, these are cubes of 40 nm in size, various sticks. And all these materials can respond differently to the action of the field, which is what we are using now. For example, sticks on the membrane of gram-negative cells under the influence of a magnetic field, this membrane is disordered. Also, these materials help the antibacterial enzyme, which is difficult to get through the surface membrane to the bacterial cell, which it must break down.
Now we have a task to get to a specific medicine, to production. This is no longer just the development of fundamental research, although it is important and we are doing it. But it is necessary to reach the production, to go through this terrible barrier between the laboratory and the production technology. Unfortunately, a lot of money is needed for this.
Portal "Eternal youth" http://vechnayamolodost.ru09.10.2014