Tuesday, September 23, 2008

Nanoparticle method may be able to inject drugs deep into the brain

Last Updated:10:01pm BST 22/09/2008

A new way to fight Alzheimer's and other neurological diseases aims to deliver a drug deep into the brain using nanoparticles

Alzheimer's is linked with the build up of damaging protein deposits in the brain and now a novel way to hinder this process is under development by a team at University College Dublin.

The team has a fundamental discovery in predicting how particles of the order of a billionth of a metre - nanoparticles - move around the body.

They report in the Proceedings of the National Academy of Sciences today that the size and the electrical charge of the nanoparticle matters, not just what it is made of.

The team found that a coating of proteins, called a corona, built up around the particles and this response mainly depends on the size and the charge of the nanoparticle.

This discovery, which shows that different sizes of the same materials pick up different proteins from the body, has a number of fundamental implications. "The find knocked my socks off," said Prof Kenneth Dawson, who led the work.

This find can be exploited to guide nanoparticles around the body.

The Dublin team is investigating how to exploit this to design nanoparticles to take an Alzheimer's drug to the brain.

Work by Prof G√ľnter Oberd√∂rster at the University of Rochester and Wolfgang Kreyling in Germany shows that nanoparticles can move into the brains of animals.

"It could change the face of health care if we learn how to exploit this potential to guide particles to important destinations in the body, such as the brain" said Prof Dawson.

"We have also now just found that certain nanoparticles are able to reverse the growth of Alzheimer plaques (the deposits of protein linked with the disease)," he said, explaining how they particles disrupt the smaller protein deposits that are thought to be the most toxic.

These experiments are only at the test tube stage, "but if we can combine the capacity of nanoparticles to get into the brain with this effect of reversing the growth of plaques that would point a way forward in these diseases."

By the same token of course, there should be caution and, as with any new technology, it must be "tested very carefully first," said Prof Dawson.

Thus, when people are exposed to nanoparticles they may penetrate into different parts of the body, with unknown health effects. So it is important to study the problems carefully, and not jump to conclusions, one way or the other, too quickly, he said.

Nanoparticles are as much as a million times smaller than the head of a pin, and have unusual properties compared with larger objects made from the same material.

The potential interactions of nanomaterials with the body and the environment have attracted increasing attention from the public as well as manufacturers of nanomaterial based products, academic researchers, and policy makers.

Nanoparticles can in principle make faster computers, and smaller mobile phones, as well as address some of the most intractable diseases. Nanotechnology is expected to become a $1 trillion industry within the next decade.

However, it is important that the be introduced safely and a new international research alliance to establish protocols for reproducible toxicological testing of nanomaterials in both cultured cells and animals was unveiled a few days ago at Nanotox 2008, a major research meeting.

This Alliance will be able to check each others work around the world, and build confidence in science, and further afield.

"When this team of scientists from Europe, the US and Japan are able to get the same results for interactions of nanomaterials with biological organisms, then science and society can have higher confidence in the safety of these materials," said Prof Dawson.

"This will open the doors to many potential benefits for society at large."


Also see The Scientist: A new twist on nanoparticle behavior

Posted by Bob Grant
[Entry posted at 23rd September 2008 04:02 PM GMT]

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.