Tuesday, November 6, 2012

Shear-activated nanotherapeutic particles (SA-NTs)

...speaking of shear stress (11/5/12). The NEJM recently put out an article highlighting research in "Shear Activated Nanotherapeutic Particles" (SA-NTs).

To condense the article... the idea is that since flow dynamics are often altered in areas of vascular pathology (see the idea of "flow separation" in yesterday's post), this microenvironment could be a way to target drug therapy.  If nanoparticles could be engineered to release fibrinolytics in areas of high shear stress (e.g. areas of stenosis), then this highly targeted t-PA drug delivery could avoid the risks of systemic t-PA. According to the article, SA-NT bound with t-PA offers the same therapeutic effect as systemic t-PA at 1/100 the dose.

An image from the article demonstrates the principle (below)

(from Ref 1)

... but since at a bifurcation of blood vessels, there are natural, nonpathologic regions of high shear stress, this raises the question why SA-NTs don't dissociate on their way to the stenosis.  According to the article, the SA-NTs are only released by "pathologically high" shear stress.

Although a promising idea, the article stresses that there is still much research to be done before SA-NTs could be used clinically.

1. Wootton DM and Alevriadou BR. "The Shear Stress of Busting Blood Clots" N Engl J Med 2012; 367:1361-136