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SPECIAL DELIVERY: “Smart bio-nanotubes” hold promise for drug, gene delivery
September 2005
by Jeffrey Bouley  | 


SANTA BARBARA, Calif.—With the publication of the August 9 issue of the Proceedings of the National Academy of Sciences, the scientific community got a sneak peek of a discovery at the University of California, Santa Barbara (UCSB), that led to the development of what are being referred to as smart bio-nanotubes.
Why smart? According to UCSB, that is because the bio-nanotubes could potentially be designed to "encapsulate and then open up to deliver a drug or gene in a particular location in the body."
The smarts of these nanotubes come, of course, from the smarts of the UCSB scientists, who reportedly found that by manipulating the electrical charges of lipid bilayer membranes and microtubules from cells, they could create open or closed bio-nanotubes, which are, essentially, nano-scale capsules.
Whether created with closed or open ends, these nanotubes could be used for drug and gene delivery applications, according to Uri Raviv, a fellow of the International Human Frontier Science Program Organization and a postdoctoral researcher in the laboratory of Cyrus R. Safinya. A professor of materials and physics and faculty member of the Molecular, Cellular, and Developmental Biology Department at UCSB, Safinya is collaborating on the nanotube effort with Leslie Wilson, professor of biochemistry in the Department of Molecular, Cellular and Developmental Biology and the Biomolecular Science and Engineering Program.
"We looked at the interaction between microtubules—negatively charged nanometer-scale hollow cylinders derived from cell cytoskeleton—and cationic lipid membranes," Raviv explains. "We discovered that, under the right conditions, spontaneous lipid protein nanotubules will form."
UCSB uses the analogy of water beading up or coating a car, depending on whether or not the car has been waxed. Likewise, the lipid will either bead up on the surface of the microtubule, or flatten out and coat the whole cylindrical surface of the microtubule, depending on its electric charge.
To close the nanotubes, the researchers added excess lipids, which makes a positively charged lipid-protein nanotube, Raviv says. To open the lipid-protein nanotubes, they added excess protein.
The next stage would be to develop other methods to control the opening and closing of the lipid-protein nanotubes, Raviv reports. It is hoped that this will allow the researchers to target the lipid-protein nanotubes to specific cells.
There are some potential pitfalls yet to address, though, in terms of human safety.
"At least 5 percent to 10 percent of the lipids we are using are positively charged lipids that could be toxic in large quantities," Raviv notes. "Although other lipid-based drug delivery vehicles typically use higher percentages of positively charged lipids, this may still limit the amount of drugs and gene that could be delivered."
Raviv says it could be years before the nanotubes have commercial market applications, and as yet, UCSB is not working with any companies to bring the discovery to market.
But the potential market applications are wide-ranging. Raviv says that any drug that can fit into the nanotubes—he says that most should—and which don't actually destroy the tubes' material are viable candidates for delivery via the nanotubes. Currently, the researchers are using the chemotherapy drug Taxol to stabilize the microtubules and to control the length of the nanotubes.
"Taxol binds to microtubules and therefore might be one of the first drugs that would be delivered in the future [via the nanotubes]," Raviv says. The concept would be to deliver the drug to the cancer cells only, he adds, thereby reducing the side effects of chemotherapy treatments.
Code: E090518



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