The thrombus will be dissolved by magnetic nanoparticles
Chemists have created a magnetically controlled drug for the treatment of blood clots
On the left: a solution of the drug together with a vascular thrombus extracted during surgery. On the right: the same system after 100 minutes. It can be seen that the thrombus is gradually dissolving. Photo: ITMO press service
ITMO University scientists together with the St. Petersburg City Mariinsky Hospital have developed a magnetically controlled drug for the treatment of thrombosis based on a magnetite matrix with an enzyme enclosed inside. The solution of nanoparticles of the drug is focused at the site of thrombus formation using a magnetic field.
In Russia, the cause of 6 out of 10 deaths is a heart attack or stroke, the two most dangerous conditions associated with vascular blockage. In order for the tissues not to die without blood flow, it is necessary to dissolve the thrombus quickly, in 3-4.5 hours, that is, to carry out thrombolysis.
To dissolve a blood clot, the patient is injected intravenously with special proteins-thrombolytics. Such drugs are administered in large doses in the expectation that a small part of them will get to the blood clot. They are quickly distributed throughout the circulatory system and provoke an immune response of the body: this worsens the patient's well-being and reduces the effectiveness of the thrombolytic.
"Now we are firing a cannon at sparrows," says Ivan Dudanov, corresponding member of the Russian Academy of Sciences, head of the regional vascular center of the City Mariinsky Hospital. – By dissolving a small blood clot that has clogged a vessel with a diameter of only 1-2 millimeters, the thrombolytic negatively affects the entire network of human blood vessels. Therefore, we decided to develop a method of local drug delivery that allows us to repeatedly reduce the dose of the enzyme, provided that the entire therapeutic effect will only be on a blood clot."
The new material consists of a porous shell based on magnetic ironstone, or magnetite, and a thrombolytic protein, urokinase, enclosed in it. Solutions of nanoparticles of such composites are injected intravenously, and then, with the help of a magnetic field, they are directed to the site of thrombus formation.
Schematic representation of a composite nanoparticle. An enzyme surrounded by a magnetite framework (brown). Image: ITMO Press Service
Such a thrombolytic, according to scientists, is suitable not only for the treatment of thrombosis, but also for prevention: artificial vessels can be covered with a composite so that they do not clog. To clear the vessels even before the formation of blood clots, the drug can be administered in small doses – the magnetite frame protects the protein inside the composite from deactivating substances and the protein works for a long time.
"Usually, when developing such materials, in order to achieve a prolonged effect, the protein is placed in a polymer matrix, from which it is gradually released, and after a while the drug turns into a dummy," says Andrey Drozdov, the first author of the work and an employee of the ITMO International Laboratory of Solution Chemistry of Advanced Materials and Technologies. – We have experimentally shown that the enzyme in the composite does not lose its therapeutic properties even with repeated use and works for a very long time. The new composite also exceeds unprotected enzymes by more than 4,000 times in terms of the rate of thrombus dissolution." An article with the results of the study was published in the journal Scientific Reports (Drozdov et al., Leach-proof magnetic thrombolytic nanoparticles and coatings of enhanced activity).
In the same laboratory, other materials are being developed for the prevention of thrombosis. So, in 2015, St. Petersburg scientists created a composite based on aluminum oxide nanorods, in the shell of which urokinase was also enclosed. This tool is proposed to be used to cover artificial vascular implants.
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21.06.2016