24 February 2015

Magnetic nanoparticles cope with blood clots in record time

Researchers at the Houston Methodist Clinic claim that the magnetic nanoparticles they developed, loaded with drugs and disguised with biochemical "camouflage", destroy blood clots 100-1,000 times faster than the approaches traditionally used for this.

These results were obtained in experiments on human blood and mouse models. Subsequent confirmation of the effectiveness of the approach in clinical trials may mean a breakthrough in the prevention of strokes, myocardial infarctions, pulmonary embolism and other life-threatening situations in which blood clots can lead to severe tissue damage and death of patients.

Each nanoparticle is a core of iron oxide (red squares), on the surface of which albumin (gray) and the anticoagulant drug tPA (tissue plasminogen activator, tissue plasminogen activator) are applied, green. The size of the side of the iron oxide cube is approximately 20 nm.

The developers applied the blood protein albumin to the surface of iron oxide nanoparticles as a kind of disguise, giving the nanoparticles time to find their target – a blood clot – before the immune system recognizes them as foreign objects. Iron oxide was chosen as the core material for a number of reasons: the possibility of application in combination with magnetic resonance imaging, remote control using external magnetic fields and additional acceleration of the destruction of blood clots due to local heating when exposed to a magnetic field.

Tissue plasminogen activator is an enzyme normally found in human blood in low concentrations. Usually, a small dose of tissue plasminogen activator is injected into the blood vessel of a stroke patient "upstream" of a suspected or confirmed blood clot. As a result, only a part of the drug reaches its target, while a significant proportion of it can move further with the blood flow, bypassing the thrombus. tPA is usually used only in critical situations, since its administration is very dangerous for patients predisposed to bleeding.

The use of tPA in combination with nanoparticles not only provides the drug with a sufficient amount of time to exert its effect, but at the same time allows you to reduce its dosage, significantly reducing the likelihood of bleeding.

First, the developers tested the ability of their nanoparticles to find a blood clot and destroy it in human blood cell cultures. After that, they conducted a series of experiments on mouse models. tPA-loaded nanoparticles were injected into the bloodstream of mice in whose vessels thrombosis was previously induced. The process of dissolution of blood clots started by them was observed using optical microscopy. According to the results obtained, nanoparticles accelerated this process by 100 times compared to what is happening in the vessels of animals of the control group.

Despite the fact that tPA is usually administered at room temperature, there is evidence that its effectiveness increases significantly when the temperature rises to 40 ° C. The researchers decided to use this phenomenon and affected the nanoparticles with external alternating magnetic fields. As a result of heating up to 42 ° C, a faster release of tPA occurred, which increased the rate of dissolution of blood clots by another 10 times (1,000 times higher than in the control group).

In the near future, the authors plan to test the safety and effectiveness of blood clot-destroying nanoparticles on other animal models and eventually conduct clinical studies of their method. They also plan to work out various options for using magnetic fields to direct the movement and heating of nanoparticles.

In general, the researchers are very optimistic about the approach they have developed, since the US Food and Drug Administration (FDA) has already approved the use of iron oxide as a contrast agent during magnetic resonance imaging. The remaining components of the nanopreparation do not need approval, since they are natural compounds included in the blood.

Article by Eszter Voros et al. TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis is published in the journal Advanced Functional Materials.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Houston Methodist via Newswise:
Magnetic Nanoparticles Could Stop Blood Clot-Caused Strokes.

24.02.2015

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