Medical Device Daily National Editor

The bloodstream is an inner sea, necessary for carrying all the materials and nutrients the body needs to the various tissues and cells. But moving always haphazardly, suffusing all, blood flow isn't a particularly effective way of getting a specific drug to particular cells of the body at a particular time.

So here's an idea: let's bind a drug to an iron particle, inject the drug and then use an external magnet to pull the drug to the particular organ of the body or particular group of cells.

Not easily done, however: this strategy hasn't worked - at least not yet.

So here's an alternative: use the magnetic approach with particles of smaller size, nano-particles. And take it a step further; use this technique to grow new nerve cells.

These are the methods being pursued – successfully, but still at the basic science/proof of concept level – by electrical engineering researchers at the University of Arkansas (Fayetteville). They have created magnetic nanotubes, combined them with nerve growth factor, and demonstrated that these materials encouraged specific cells to differentiate into neurons.

This is the first step, via in vitro work, on the path to an important potential clinical application: the treatment of neurodegenerative disorders such as Parkinson's and Alzheimer's disease.

The technique, they hope, will be developed into a method for delivering nerve growth factor to a particular region of the brain or spinal cord to grow new nerve cells or repair them.

Jining Xie, assistant professor at the University of Arkansas and lead author of the study, told Medical Device Daily that the nanotubes may be significantly more useful for the magnetic drug-delivery approach than the larger iron particles that have been employed as drug-loaded systems pulled about by a magnet.

The nanotubes were created – or "functionalized, using Xie's term – in the research group's lab, starting with basic iron oxide materials and then using a chemical method to reduce them to what he called an "ion-salt."

"Due to their structure and properties, magnetic nanotubes are among the most promising candidates of multifunctional nanomaterials for clinical diagnostic and therapeutic applications," he said.

In solution, the nanotubes then were applied to rat pheochromocytoma, technically known as PC12 cells.

Xie said the PC12 cells were chosen because they require nerve growth factor – a small, secreted protein that helps nerve cells survive – to differentiate into neurons.

The nervous system, of course, depends upon a network of neurons tied to each other by synapses, with these synaptic connections occurring through neurites, which are immature, developing neurons.

The nervous system fails as a result of the injury or disruption of these cells and the interferences within the neural network.

The researchers were hoping to see – and did see – nerve growth that would indicate interactions between the PC12 cells and the nanotubes.

Specifically, they observed the growth of a type of neurite known as filopodia, appearing as slender projections that extend from the leading edge of migrating cells – extruding from neurite growth cones toward the nanotubes incorporated with nerve growth factor.

"Microscopic observations," Xie said, "showed filopodia extending from the growth cones were in close proximity to the nanotubes, at times appearing to reach out toward or into them."

Xie said that development of these cells was normal, indicating that there was no toxicity.

The next step, he said, is to move forward on a proposal to work with biological faculty and researchers at the University of Arkansas to test the method in animal models. Besides being useful for delivery of nerve growth materials, the hollow architecture of the nanotubes, Xie said, enable the insertion of drugs, and then an external magnetic field could be used to control their movement within the body.

Looking to the longer term, Xie acknowledged that in order to reach clinical applications in humans, the use of nanotubes and other nanomaterials – like the use of stem cells for broad clinical use – faces a major hurdle: the scale-up of enough material, at low enough cost, to make them broadly usable.

"This is a major problem for all nanotechnology – the cost," he told MDD. "What we made in the lab is lab-scale. But for the future of commercialization, we need to produce this material at low cost." And he said that this is one of the objectives of further research.

The study by Xie appears in Nanotechnology, a journal of the Institute of Physics (London).

Xie developed the study with research partners Malathi Srivatsan, associate professor of biology at the University of Arkansas, and Linfeng Chen, senior research associate at the Center for Wireless Nano-, Bio- and Info-Tech Sensors and Systems at the university.

Last August, this center held a one day workshop at the university's Winthrop Rockefeller Center (Morrilton, Arkansas), focusing on new development for what it called the "nano-bio-infotechnologies-based sensors and systems in engineering and medicine.

The conference explored the possibilities for using technologies based on nanosensors and nanoelectronics devices with wireless communication capabilities that could have significant impact in broad range of applications in human healthcare, national security and environmental monitoring.

Engineering researchers at the university also have published a textbook titled Nanomedicine – Design and Application of Magnetic Nanomaterials, Nanosensors and Nanosystems, describing it as a comprehensive treatment of how nanotechnology may impact a variety of therapies.

(MDD Nanotechnology R&D Report 2009 reports on activity in the nanotechnology sector. For more information, call 800-688-2421 or 404-262-5476.)