Researchers hoping to develop nanoparticles as medicines or carriers of therapeutic molecules have much more to worry about than the type of material they plan on miniaturizing, according to a study in this week's issue of the Proceedings of the National Academy of Science.

Researchers in Ireland found that the corona, or cloud of proteins and other biomolecules that adheres to a nanoparticle immersed in biological media (in this study human blood plasma), changes depending on the size of the nanoparticle and the charge on its surface. That, in turn, can affect the particles' therapeutic action in the body.

Nanotechnology is "an enormously powerful tool, but we need to know how to control it," Kenneth Dawson, a University College Dublin physical chemist and the study's senior author, told The Scientist. "We have to look at what's happening at the surface of these materials rather than just the materials themselves. It's a new science really."

According to Dawson, the study represents a "paradigm shift" in how chemists typically think about the interaction of nanoparticles in biological settings. Traditionally the composition of the nanoparticle itself was thought to be the most important safety and functionality consideration. With Dawson's paper, the importance of the corona, and the physical factors which shape it, comes to the fore.

"The biological identity of a particle depends not only on its own material, but also what it picks up in the surroundings," Dawson said.

Dawson and his group last year coined the term "corona" for the conglomeration of proteins adhering to nanoparticles in biological media. Since then, the group has been exploring the properties of coronas. In the present study, the researchers found that nanoparticles introduced, in vitro, to human plasma accumulated markedly different coronas depending on their size and charge.

For example, his team found that uncharged particles attracted more immunoglobulins while charged particles pulled in more fat-shuttling proteins. "They pulled on quite different proteins," Dawson explained.

This, Dawson said, could have major implications for nanoparticles used as human therapeutics. For example, a particle of one size and surface charge might be trafficked to the brain of a patient, while another particle of a different size and charge, even though it's made of the same material, might be shuttled to the liver. "[A nanoparticle] can go places you didn't want it to go, and when it gets there it might pick up different signals that can be confusing," he said.

Drug makers and regulators should consider the effects of nanoparticle size and surface when developing and monitoring therapies that use nanotechnology, he added.

University of Rochester professor of environmental medicine and toxicology Gunter Oberdorster, who was not involved in the study, noted that drug makers may be able to make use of the differing physiological effects different coronas have on a nanoparticle's fate in the body. "Nanomedicine may take advantage of this and target a specific organ." While he called Dawson's study "an important step," he cautioned that in vivo studies must confirm the effects of nanoparticle size and surface character in living organisms.

According to Dawson, other researchers are conducting preliminary in vivo studies in mice to explore how nanoparticle sizes and surface properties affect the physiological activity of the tiny particles in living systems.

Although no treatments or therapeutics that use nanoparticles are currently on the market, experimental cancer treatments and other nanotechnology-based therapies are nearing FDA approval, according to Rice University chemist and Director of the International Council on Nanotechnology, Kristen Kulinowski. "This [study] bolsters the argument about the vital need for good, quality characterization [of nanomedicines], the actual species the body will experience," she told The Scientist.