Nanotherapeutics: tiny particles reach places other drugs can't access

05 July 2012
Posted by Chris Smith.

A nanoscale solution to unclogging blocked blood vessels has been revealed by scientists this week.

Dubbed SANTS - shear activated nanotherapeutics - these particles, which are roughly a thousandth of a millimetre across or about same size as a blood platelet, are made by Embolus to the superior mesenteric arterydrying a fine spray of the chemical polylactic co glycolic acid (PLGA). This results in loosely-bound aggregates of much tinier particles that attract and bind one another hydrophobically.

Critically, these aggregates remain bound together when flowing around the bloodstream under normal conditions. But when they pass through areas of high shear stress or turbulence, caused for instance by a blood clot that has narrowed a blood vessel, the particles break up, dispensing as they do so any chemical cargo that has been coupled to them.

In initial tests using an artificial blood vessel containing a narrowed region simulating a 90% obstruction, Donald Ingber and his team at Harvard showed that, in the region of the blockage where the shear forces on fluid flowing past were more than 10 times normal, this provoked infused SANTs to disaggregate in the region of the obstruction.

Next the team prepared SANT particles that were each loaded with 500,000 molecules of a clot-dissolving protein called tPA (tissue plasminogen activator). These SANTs were able to clear blood clots from abdominal vessels and even dissolve clots obstructing the arteries of the lungs (known as pulmonary emboli) in experimental mice.

Critically, none of the treated animals developed bleeding from any other sites in the body, proving that deployment of the clot-busting treatment was being selectively restricted to those regions where the agent was needed.

This is a significant improvement on current anti-thrombolytic therapies for heart attacks and strokes where clot-dissolving drugs are injected intravenously and can hence affect every tissue, potentially precipitating haemorrhages at other sites including in the brain or intestines.

The next step will be to test the technique on humans. But, as the team point out in their paper in Science this week, before this can occur, a safer way to couple the anti-clot chemicals to the nanoparticles will need to be found. The system they have tested uses a form of molecular velcro called streptavidin-biotin, but this can trigger an immune response, potentially limiting the use of the therapy.

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