Nanoparticles: size and charge matter

It’s not so much what the tiny particles are made of, but how they interact with proteins in the blood, that can determine the particles’ fates as couriers of specific treatments for disease

Normal 0 false false false MicrosoftInternetExplorer4 Before you trust a medical nanoparticle, you should know what kind of riffraff it hangs out with.

Larger than a protein but much smaller than a bacterium, medical nanoparticles are tiny, synthetic vessels that scientists design to carry drugs, genes or other therapeutic compounds into the body. As these particles travel in the bloodstream, proteins that glom on can dramatically affect whether the particles will be healing or toxic.

New research reveals how the size and electric charge of nanoparticles determine which proteins will latch on — knowledge of a little-studied phenomenon that could help scientists design nanoparticles to treat diseases such as cancer.

“It has often been thought that we should think of nanoparticles in terms of the materials they’re made from,” says Kenneth Dawson, director of the Centre for BioNano Interactions at University College Dublin in Ireland. But the size and charge of the particles, and how those factors influence the kinds of proteins that bind to them, is just as crucial. “When they go into living environments, the nanoparticles pick up a small number of molecules, mainly proteins, that stick pretty strongly.”

“For many practical purposes [nanoparticles are] probably seen by your body not as the original material but as what they picked up,” says Dawson, coauthor of the new study published online September 23 in the Proceedings of the National Academy of Sciences.

Over the last 10 or so years, researchers have made nanoparticles from a wide variety of materials, such as fat molecules, silicon or carbon nanotubes. By dotting the surfaces of these nanoparticles with molecules that bind to, say, cancer cells, scientists hope that these tiny vessels will deliver a disease-fighting drug only to cells that need it. For cancer patients, such focused treatment could alleviate many of the unpleasant side effects of chemotherapy.

While these therapies have seen some preliminary success in lab animals, results in humans have been mixed. Dawson says part of the problem could be that scientists don’t yet understand which blood proteins will coat a given nanoparticle and why.

The proteins coating nanoparticles “would affect what tissues they’re going to stick to and how they’re going to get eliminated from the body,” comments Leigh Anderson, an expert in plasma proteomics, the study of the suite of proteins that float freely in the blood. He is also CEO of the Plasma Proteome Institute, a nonprofit research institute in Washington, D.C. “That’s always been treated as a black art, and this research is subjecting the question to a rigorous analysis.”

Dawson’s team suspended polystyrene spheres of two sizes — 50 nanometers and 100 nanometers — in human blood plasma. For each size, the particles’ surfaces had a positive, negative or neutral electric charge.

Despite being made from the same material, the smaller and uncharged spheres each attracted more proteins from the immune system, and the larger and charged spheres each attracted more fat-transporting proteins.

“I think it shocks the socks off me” that particle size makes such a big difference, Dawson says.

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