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Tuesday, January 22, 2008

Nanomaterials used to localize and control drug delivery

Nanoscale polymer films, about four nanometers per layer, were used to build a sort of matrix or platform to hold and slowly release an anti-inflammatory drug. The films are orders of magnitude thinner than conventional drug deliver coatings, said Genhong Cheng, a researcher at UCLA’s Jonsson Comprehensive Cancer Center and one of the study’s authors. A nanometer is one billionth of a meter.

“Using this system, drugs could be released slowly and under control for weeks or longer,” said Cheng, a professor of microbiology, immunology and molecular genetics. “A drug that is given orally or through the bloodstream travels throughout the system and dissipates from the body much more quickly. Using a more localized and controlled approach could limit side effects, particularly with chemotherapy drugs.”

Researchers coated tiny chips with layers of the nanoscale polymer films, which are inert and helped provide a Harry Potter-like invisibility cloak for the chips, hiding them from the body’s natural defenses. They then added Dexamethasone, an anti-inflammatory drug, between the layers. The chips were implanted in mice, and researchers found that the Dexamethasone-coated films suppressed the expression of cytokines, proteins released by the cells of the immune system to initiate a response to a foreign invader. Mice without implants and those with uncoated implants were studied to compare immune response.

The uncoated implants generated an inflammatory response from the surrounding tissue, which ultimately would have led to the body’s rejection of the implant and the breakdown of its functionality. However, tissue from the mice without implants and the mice with the nano-cloaked implants were virtually identical, proving that the film-coated implants were effectively shielded from the body’s defense system, said Edward Chow, a former UCLA graduate student who participated in the study and is one of its authors.

The nanomaterial technology serves as a non-invasive and biocompatible platform for the delivery of a broad range of therapeutics, said Dean Ho, an assistant professor of biomedical and mechanical engineering with the McCormick School of Engineering and Applied Science, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the study’s senior author.

The technology also may prove to be an effective approach for delivering multiple drugs, controlling the sequence of multi-drug delivery strategies and enhancing the life spans of commonly implanted devises such as cardiac stents, pacemakers and continuous glucose monitors

Friday, January 18, 2008

Magnetic Nanoparticles could be used to control uptake of drugs by cell receptors

For the first time, researchers have demonstrated a means of controlling cell functions with a physical, rather than chemical, signal. Immune cells coated with nanoparticles take up calcium in the presence of a magnetic field. Each nanoparticle measures approximately 30 nanometers in diameter.

In this image, yellow cells are taking up calcium in response to a localized magnetic field. Cells that are farther away from the field are shown in purple and do not take up calcium. Credit: Donald Ingber, Harvard Medical School

Using a magnetic field to pull together tiny beads targeted to particular cell receptors, Harvard researchers made cells take up calcium, and then stop, then take it up again.

This is another important step to cellular and molecular control to enable nanomedicine

Ingber's group demonstrated its method for biomagnetic control using a type of immune-system cell that mediates allergic reactions.
Targeted nanoparticles with iron oxide cores were used to mimic antigens in vitro. Each is attached to a molecule that in turn can attach to a single receptor on an immune cell. When Ingber exposes cells bound with these particles to a weak magnetic field, the nanoparticles become magnetic and draw together, pulling the attached cell receptors into clusters. This causes the cells to take in calcium. (In the body, this would initiate a chain of events that leads the cells to release histamine.) When the magnetic field is turned off, the particles are no longer attracted to each other, the receptors move apart, and the influx of calcium stops.

"It's not the chemistry; it's the proximity" that activates such receptors, says Ingber.

The approach could have a far-reaching impact, as many important cell receptors are activated in a similar way and might be controlled using Ingber's method.

"In recent years, there has been a realization that physical events, not just chemical events, are important" to cell function, says Shu Chien, a bioengineer at the University of California, San Diego. Researchers have probed the effects of physical forces on cells by, for example, squishing them between plates or pulling probes across their surfaces. But none of these techniques work at as fine a level of control as Ingber's magnetic beads, which act on single biomolecules.

Many drugs, from anticancer antibodies to hormones, work by activating cell receptors. Once a hormone is in the blood, however, there's no turning it on or off. "This shows that you can turn on and off the signal, and that you can do it instantly," says Christopher Chen, a bioengineer at the University of Pennsylvania. "That's something that's hard to do, for example, with an antibody."

Ingber has many ideas for devices that might integrate his method of cellular control. Magnetic pacemakers could use cells instead of electrodes to send electrical pulses to the heart. Implantable drug factories might contain many groups of cells, each of which makes a different drug when activated by a magnetic signal. Biomagnetic control might lead to computers that can take advantage of cells' processing power. "Cells do complex things like image processing so much better than computers," says Ingber. Ingber, who began the project in response to a call by the Defense Advanced Research Projects Agency for new cell-machine interfaces, acknowledges that his work is in its early stages. In fifty years, however, he expects that there will be devices that "seamlessly interface between living cells and machines."

Harvard Institute for Biologically Inspired Engineering.