Zapping Deadly Blood Clots Just Got a Thousand Times Faster

​Once the s​ymptoms of a stroke begin—your face begins to droop, an arm feels suddenly weak, you find yourself struggling to speak—you have less than six hours to get to a medical center for treatment. That six hour window is the magic number: Patients treated soon after the onset of a stroke are more likely to survive and less likely to suffer disabilities after three months.

Fortunately, researchers at the Houston Methodist Research Institute have developed a new system that delivers brain-saving drugs up to 1,000 times faster using nanoparticles,miniscule magnetic objects that can ferry medication safely through our blood.

It is a long way from use in emergency rooms, but in a scenario where every minute that passes translates to lost brain cells, this is an exciting addition to the possible applications of nanotechnology in health care.

The majority of strokes are caused when a blood clot develops in an artery and blocks blood flow to the brain. The current standard treatment is rapid administration of tissue plasminogen activator (tPA), a key protein in the body's natural process of breaking down blood clots.

The tPA is injected directly into the bloodstream, quickly dissolving the clot, clearing the vessel, and restoring blood flow. The free floating tPA affects the entire circulatory system though, so it is not without side effects—administration of the drug can cause excessive bleeding.

The new resea​rch, published in the journal Advanced Functional Materials, introduces a method of tPA delivery that uses biodegradable nanoparticles (tPA-NC) to send the clot-busting tPA directly to the site of the dangerous clot. The particle is cloaked in the protein albumin; this camouflage allows it to move stealthily through the body, evading attack by the immune system.

At 150 nanometers wide each, the nanoparticles are almost mind-bogglingly small, roughly 1/50th the size of a human red blood cell.

For this experiment, researchers created an arterial clot in a mouse to study the effect of the particles in a live model. They found that, in addition to being much faster, the new method may reduce the overall risk of bleeding.

"We have designed the nanoparticles so that they trap themselves at the site of the clot, which means they can quickly deliver a burst of the commonly used clot-busting drug tPA where it is most needed," the study's co-principal investigator, Paolo Decuzzi, explain​ed to Science Daily.

This will allows doctors to use a lower dose of the drug, decreasing the risk of hemorrhage and opening up tPA treatment to patients previously considered ineligible for use of the drug due to their risk of bleeding. Because of the iron core, researchers believe these nanoparticles can be guided directly to the site of the clot using an external magnetic field, focusing the drug onto the dangerous clot and further reducing the risk of bleeding.

The iron core has another advantage. Prior studies have shown that tPA functions most effectively at 104 degrees Fahrenheit. Researchers applied alternative magnetic fields to generate heat at the site of the clot (and, by extension, the location of the tPA-NCs). At this increased temperature, the tPA dissolved the clot ten times faster than when left at body temperature.

These findings are encouraging, not just for patients suffering from stroke but also for those with a host of other conditions involving blood clots including heart attacks, pulmonary emboli, and deep vein thromboses.

That said, human trials are a few years off and it is far too early to start fantasizing about redesigning stroke centers. A particular challenge will be visualizing the site of the blood clot in the human body. One significant scientific hurdle has already been cleared, though: All elements of the nanoparticle—iron oxide, albumin, and tPA—have a high safety index and are FDA-approved for clinical human use.

If the nanoparticles are effective in human trials, they could greatly improve our ability to prevent and reduce the tissue damage that can result from blood clots. Similar nanoparticles could be used to deliver chemotherapy directly to the site of a tumor or antibiotics to the site of infection. If human clinical trials are successful, creative researchers and health care professions could be adopting nanoparticles for novel uses for generations to come.