Trojan Pill: Continued
A pill for the cellSoon the treatment will become targeted – ultrasound will help deliver the drug to the diseased organ with filigree accuracy
Alla Astakhova, "Results" No. 42-2010
This was the age-old dream of pharmacists: to create an ideal pill that would begin to act in the patient's body not immediately, but at the moment when the medicine reaches the diseased organ. Recent experiments on gene therapy require an even more targeted hit – to cure the disease at the root, you need to deliver the medicine directly to the affected cell. Help came to the doctors from where they did not expect: from specialists in tomography and ultrasound.
It all started some time ago, when experts were hearing experiments with the production of graphene – the thinnest layer of graphite. Attempts by Andrey Geim and Konstantin Novoselov later ended in success. Gleb Sukhorukov, a graduate of the Physics faculty of Moscow State University, also caught fire with the idea of creating the thinnest films, this time polymer. They were supposed to be like puff pastry – with layers of either positively or negatively charged polymer actually one molecule thick. At first, the idea seemed incredible: from the point of view of strict theory, it is still believed that such films cannot be assembled ("Results" No. 17-2010, "Trojan Pill"). However, it still happened – the discovery of Gleb Sukhorukov, now the head of the biopolymer group at the Faculty of Materials Science at Queen Mary College of the University of London, turned the ideas of many. Of course: it turned out that the state of the materials collected in this way can be programmed depending on which polymers are included in their composition. For example, some polymers contract or expand under the influence of certain temperatures or radiation. Others may disintegrate depending on different conditions. It turns out that their behavior can be controlled. When tiny balls were first assembled from new materials, the idea of a completely new "Trojan pill" gradually began to emerge. It could begin its work in the body not immediately, but "by order" – having reached the desired organ.
At the same time, a unique filling for the magic pill arrived. Of course, the possibility of targeted drug delivery to a certain organ is in itself a revolution in medicine, because it allows you to reduce doses many times and remove side effects. However, there are drugs that can get into the body this way and only this way. We are talking about gene therapy. The most promising developments in this field are based on the discovery of 2006 Nobel laureates Andrew Fire and Craig Mellow, who established a universal mechanism for regulating gene activity in living beings based on RNA interference. It's no secret that many diseases are associated with the fact that certain genes are too active: too much protein encoded by one or another gene appears in the body, which causes harm. It is here that the cause of many heart and vascular diseases, oncological diseases, metabolic disorders lies. By removing the activity of genes or, as experts say, by reducing their expression, you can cure the disease at the root. To do this, scientists have proposed introducing so-called micro-RNA into the affected organ. Each organism produces hundreds of types of such RNAs. Their main purpose is to silence genes: that is why, although the nucleus of every cell in our body contains the entire composition of genes, they do not work everywhere and in different ways. The idea was as follows: if there is not enough micro-RNA in the human body and this causes the disease, then the necessary RNA can be synthesized and injected into the body. Scientists went further and learned how to change the resulting RNA by chemical means. Recently, the American biopharmaceutical company RXi Pharmaceuticals has patented such RNA molecules that can become a medicine - they practically do not change their properties in biological fluids, do not affect the human immune system.
However, this does not solve all the problems associated with treatment. In fact: overexpression of genes leading to the disease is observed only in certain organs and tissues of a person. In other parts of the body, the same micro-RNAs may not be needed, and possibly harmful. Similar problems have been observed in other studies related to gene therapy. Another American biotech company, GlyGenix Therapeutics, has begun experiments to treat the "breakdown" of the G6Pase gene associated with the regulation of glucose levels in the body. To do this, it was necessary to deliver the "correct" DNA to the patient's liver. How will the medicine hit exactly the target, where it is needed, and even into human cells? Scientists have been struggling with this question for a long time. First, the genetic material was tried to be delivered to the body by "sewing" it into some safe virus that infected the patient's cells. However, in this case, it was impossible to think about the exact delivery to a certain body. But a solution was found. It seemed paradoxical, but the more researchers looked at it, the more advantages they found.
It was about tiny "Trojan" capsules containing gas. The Dutch company Philips has already used such for diagnostic purposes. Under the influence of focused ultrasound radiation, the capsules were able to "explode", releasing a gas that could serve as a contrast agent for ultrasound diagnostics. Philips Research researchers realized that they could use these properties to improve drug delivery to the body. How? The results of the experiments revealed one curious circumstance that has not yet been fully explained. "Exploding" and being released from the capsules, the gas disintegrated into many tiny bubbles. The bubbles hit the walls of the cells of the body, at some point making them more permeable - and the drug could penetrate inside. "The development of ultrasound technologies capable of noninvasively delivering new drugs to the right organ opens up amazing opportunities for the development of medicine focused on individual patient needs," says Henk van Houten, Senior Vice President of Philips Research and head of the Philips Healthcare Research program.
Scientists have created a whole technique of "targeted" drug administration under the influence of ultrasonic waves, which is called sonophoresis. To do this, they used two types of "Trojan pills". The first ones, very tiny, ranging in size from 100 to 2000 nanometers, are filled with medicine. They are so small that they can easily travel through the body with the flow of blood, penetrating even the thinnest capillaries. The capsule shell can be assembled from substances capable of heating up under the influence of electromagnetic radiation. Therefore, the doctor tracks their movement through the body in real time using a tomograph that records changes in the temperature of body tissues. As soon as the capsules get into the right organ, they can be "opened" using the directional action of ultrasound. In this case, the medicine will come out of the capsules and begin to act. But that's not all. To inject the drug directly into human cells, Philips Research specialists use other capsules, larger in size – 4 micrometers. They do not contain medicine, but gas. At the moment when the capsules "explode" under the influence of ultrasound, the cell walls change, and the drug penetrates inside.
Fiction? Several drugs whose action is based on this principle have already passed preclinical tests. Quite a bit, and healthy volunteers will try a new technique in the interests of humanity. This means that victory over previously incurable diseases is not far off. This will definitely happen if ultrasound helps gene therapy.
Portal "Eternal youth" http://vechnayamolodost.ru18.10.2010