Nanoparticles Target Damaged Blood Vessels

Posted on May 1st, 2014 by Dr. Francis Collins

Cardiovascular disease (CVD) is the number one killer of Americans. There are, in fact, many types of CVD—but common to most of them is damaged blood vessels. Stents can be inserted to prop open collapsed or narrowed arteries, and deliver drugs inside vessels. But, so far, we haven’t been able to repair the damaged vessels themselves. Researchers in an NIH-funded team of bioengineers at Clemson University, in South Carolina, are among those who believe that delivering drugs directly to the site of damage to mend the vessel might boost our ability to treat CVDs. And they’ve devised a way to deliver such drugs right where they want them: using specially-crafted nanoparticles.

These nanoparticles work by exploiting a common feature of CVD-damaged vessels. The middle layer of healthy blood vessels includes smooth muscle cells and the elastic lamina, rubber band-like fibers that enable vessels to dilate and constrict. In damaged vessels, fibers are fragmented, and the sugar-protein molecules that typically coat healthy elastin fibers are degraded—leaving the fibers naked. The Clemson team identified an antibody protein that recognizes the naked elastin fibers, but not the healthy, coated ones. They tethered the antibody to a biodegradable nanoparticle—just 200 nanometers in diameter (about the size of a very small microbe). The antibody, with nanoparticle attached, then sought out the damaged regions of blood vessels, found them, and stuck to them: a targeted, special-delivery system, for use with drugs or imaging agents.

The researchers tested the antibody-guided nanoparticles in rat models of atherosclerosis, calcified arteries, and aortic aneurysms. They injected the particles into the animals and waited. After 24 hours, fluorescent markers attached to the antibodies confirmed that the nanoparticles targeted only the damaged vessels—not the healthy ones.

This new delivery system may prove especially useful for patients with CVD. Our bodies can’t repair the damaged blood vessels without help: adults can no more generate elastic lamina than they can sprout new limbs. Using these nanoparticles to deliver drugs may enable medical treatment without requiring surgical interventions. Fixing the vessels may ultimately reverse the course of the disease.

In fact, the Clemson team is now working on loading these nanoparticles with new drugs that will directly target and repair the damaged tissue, reducing side effects to other tissues and organs. If tests in animal models are successful, these antibody-targeted nanoparticles could be bound for human trials in a few years.

Reference:

[1] Nanoparticle targeting to diseased vasculature for imaging and therapy.Sinha A, Shaporev A, Nosoudi N, Lei Y, Vertegel A, Lessner S, Vyavahare N. Nanomedicine. 2014 Feb 22.

Links:

Naren Vyavahare, Clemson University

Nanomedicine, NIH Common Fund

Nanotechnology 101, National Nanotechnology Initiative

NIH support: National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences