Nanoparticles that clear blood clot — Shear-activated nanotherapeutics
Blood-vessel blockages are one of the leading causes of death worldwide and often lead to long-term adult disability, if not death. The major threats are the obstructions in the blood vessels of the brain (ischemic stroke), heart (coronary infarction), and lungs (pulmonary embolism).
Fortunately, there is treatment available for these conditions, although it can be problematic. The treatment for blood vessel clots involves the administration of thrombolytic drugs. These drugs break down blood clots – an action referred as “clot busting.” The caveat is the risk of bleeding since thrombolytic drugs are distributed throughout the body, breaking down even the good blood clots that prevent us from bleeding to death and promote injury repairs. Another issue is that the drugs typically need to be applied within few hours of the onset of symptoms, but the drugs are usually administered in hospital settings, making immediate treatment difficult.
To circumvent these issues with the current treatment option, a team of scientists in Boston has developed a potentially more efficient treatment, which they call shear-activated nanotherapeutics.
The researchers sought after a targeting mechanism that will deliver drugs to blocked blood vessels. Shear-activated nanotherapeutics consist of aggregates of nanoparticles (NPs) that break up into smaller components when they are exposed to high fluid-shear stress (see the next paragraph for more details). In authors’ own words, the NPs are “much like a wet ball of sand disperses into individual grains when rubbed in one’s hands.” Upon breakage, the NPs adhere to the site of clot. The NPs are coated with tissue plasminogen activator (tPA) which is an FDA-approved thrombolytic drug (meaning that tPA is already being used for treatment of blood vessel clots). Because the NPs specifically adhere to the sites where blood vessels are constricted, in theory, they can deliver tPA more efficiently than just tPA on its own.
The new approach was inspired by a natural mechanism in the body, in which platelets (specialized blood cells) gather and attach to the regions of blood vessels that are constricted. (This is one of the first steps in the formation of blood clots.) The regions of narrowed blood vessels experience high fluid-shear stress. In this case, fluid-shear stress is caused when blood passing through in the vessels applies stress (or force) along the surfaces of the vessels. It’s the same concept when we clean a dirty pipe by making the water run through really fast; the water rushing through the inside of the pipe scrapes off the surface clean. High fluid-shear stress is a unique trait of clotted blood vessels that set them apart from healthy, normal blood vessels. In constricted vessels, local fluid-shear stress can be 10-100 times higher than normal.
To prove the efficiency of their new approach, the scientists injected mice having pulmonary embolism (clotted blood vessels in the lung) with shear-activated nanotherapeautics. The clot was rapidly dissolved, and the blood flow returned to normal. Whereas none of the mice without the treatment survived more than 1 hour, 80% of the treated mice survived. In addition, the treatment with shear-activated nanotherapeautics was much more effective than treatment with tPA alone. In fact, tPA alone had negligible effects at the concentration used in shear-activated therapeautics.
The researchers are hoping that this approach will serve as a new treatment method for blood vessel blockages. The main advantage of this method is that, by targeting the drugs specifically to the site of blood flow obstructions, only a fraction of the regular tPA dosage is required. Also, because the aggregated NPs are so much bigger in size than tPA alone, they should remain in the blood rather than diffusing into other tissues and causing problems. In addition, NPs are rapidly cleared from the circulation: 80% clearance in 5min. All in all, these traits would minimize unwanted bleeding caused by thrombolytic drugs.
Of course, this is still a preliminary report, and more future studies are needed before the new treatment can be applied to patients. But the new method seems promising in that it has broad applications, targeting regions of constricted blood vessels regardless of the causes or locations. The authors of the study anticipates that the treatment can be used not only for patients with pre-existing clots (such as stroke or heart diseases), but can also be applied as an immediate “first aid” administration to patients suspected of life-threatening blood clots even before they arrive to hospitals.
Thank you for reading the post, and see you next week! 🙂