Scientists have developed a nanoparticle that was able to specifically inhibit neutrophils – a type of white blood cell that plays important roles in infection and inflammation – from exiting out of blood vessels and into tissues to cause inflammatory damage. In animals with an experimentally induced version of sepsis, they found that treatment with the particles reduced injury to the lungs.

The findings, Asrar Malik told BioWorld Today, were “based on our longstanding interest in albumin as a carrier molecule.” Albumin’s role in the body is to function as a delivery vehicle, getting hormones, lipids and other biological molecules to where they are needed.

Malik is at the University of Illinois at Chicago and the senior author of the findings, which appeared in the Feb. 23, 2014, online issue of Nature Nanotechnology.

Malik and his team were trying to use albumin nanoparticles to deliver materials into endothelial cells, which make up the lining of blood vessels, in the hopes of being able to transport materials across the vascular barrier.

But instead, they made the serendipitous discovery that the nanoparticles specifically attached to neutrophils that were themselves attached to blood vessel walls. And that opened up the possibility of specifically targeting such cells.

Neutrophils patrol the bloodstream and aggregate at the sites of tissue injury, where they take care of bacterial debris. The problem comes when the inflammation that attracts the neutrophils is either chronic or excessive. The latter is the case in sepsis, which is an out-of-control inflammatory response that can be set off by a multitude of factors, though it is most often due to infection. Sepsis is a major cause of death in intensive care units; the National Institute of General Medical Sciences estimated that the condition kills several hundreds of thousands of Americans annually.

Part of the reason sepsis is such a problem is that since the market withdrawal of activated protein C, no specific treatments exist for the condition. Treatments focus on eliminating the underlying infection, and on preventing the dangerous blood pressure drops that can kill sepsis patients. But dozens of clinical trials have failed to yield an FDA-approved medication for sepsis itself.

One of the frequent, and more dangerous, symptoms of sepsis is acute lung injury. When neutrophils attach to the blood vessels in large numbers, they can make it difficult to breathe by impairing the transfer of gases between the lungs and the blood.

When neutrophils attach to the blood vessels, however, they become activated. Part of that activation is that they start expressing certain receptors that are not found on circulating neutrophils.

Malik and his team first showed that their nanoparticles bound specifically to such activated neutrophils. They then went on to use the nanoparticles to deliver a drug that could pry the cells back off of the blood vessels, in what Malik described as a “Trojan horse mechanism.”

That drug was the resveratrol analog Zeptol (piceatannol), which blocks a kinase that neutrophils use to get into tissues. Blocking the kinase had the neutrophils returning into the circulation instead. The drug did not affect neutrophils that were not attached to vessel walls, which suggests it would allow those cells to keep up immunosurveillance in the bloodstream.

Malik said that besides sepsis, the team hopes to apply their nanoparticles to another type of wandering cells: cancer cells that have broken off from a primary tumor and are in the process of establishing metastases.

The process of metastasis has cells leaving the primary tumor, traveling through the bloodstream as circulating tumor cells for a time, and ultimately crossing back out of the bloodstream and into distant tissues to start metastases.

Such circulating tumor cells, too, start expressing FC-gamma receptors – the receptors that are important for making cells take up the albumin nanoparticles – when they are getting ready to leave the bloodstream. If such nanoparticles could deliver toxins to cells that are in the process of leaving the bloodstream, they could nip metastases in the bud before they have a chance to become established.

His team has used the particles to deliver dye as well as Zeptol, and he said that they would likely be able to deliver a wide variety of drugs. “We think this is a generally applicable principle.”