Editorial Feature

“Smart” Bio-Nanotubes Could Improve Drug and Gene Delivery Systems

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At the University of California, Santa Barbara, materials scientists along with biologists have created “smart” bio-nanotubes having open or closed ends, which could be further developed for gene or drug delivery applications.

In the future, nanotubes could be built to incorporate a gene or drug, and deliver them to specific locations in the body, making nanotubes “smart.” The researchers have discovered that open or closed bio-nanotubes, or nanoscale capsules, could be developed by controlling the electrical charges of lipid bilayer membranes and microtubules from cells.

The finding has been reported in one of the articles in the Proceedings of the National Academy of Sciences, in its August 9th 2011, issue. The article can be accessed online from the PNAS Early Edition.

The finding is the result of collaboration between two laboratories. One is of Cyrus R. Safinya, professor of materials and physics, and faculty member of the Molecular, Cellular, and Developmental Biology Department. The other is of Leslie Wilson, professor of biochemistry in the Department of Molecular, Cellular, and Developmental Biology, and the Biomolecular Science and Engineering Program.

Uri Raviv, a post-doctoral researcher in Safinya’s lab and a fellow of the International Human Frontier Science Program Organization, is the first author of this article. Daniel J. Needleman, formerly Safinya’s graduate student who is now a postdoctoral fellow at Harvard Medical School; Youli Li, a researcher in the Materials Research Laboratory; and Herbert P. Miller, a staff research associate in the Department of Molecular, Cellular, and Developmental Biology, are the other co-authors.

The microtubules used by the scientists for their experiments were purified from the brain tissue of a cow. These microtubules are nano-scale hollow cylinders obtained from the cell cytoskeleton. Microtubules and their assembled structures in an organism are critical components in performing cell functions that broadly range from providing tracks for the transport of cargo to forming the spindle structure in cell division. In addition, they perform the function of transporting neurotransmitter precursors in neurons.

In our paper, we report on a new paradigm for lipid self-assembly leading to nanotubule formation in mixed charged systems,” stated Safinya.

We looked at the interaction between microtubules—negatively charged nanometer-scale hollow cylinders derived from cell cytoskeleton—and cationic (positively charged) lipid membranes. We discovered that, under the right conditions, spontaneous lipid-protein nanotubules will form,” explained Raviv.

The scientists cited the example of water beading up or coating a car, based on whether the car was waxed or not. Similarly, based on the charge, the lipid will either bead up on the microtubule’s surface or level off and coat its entire cylindrical surface.

Raviv explained that the new type of self-assembly is due to an extreme mismatch between the charge densities of cationic lipid and the microtubules. “This is a novel finding in equilibrium self-assembly,” he added.

According to the authors, the nanotubule including a three-layer wall seems to be the means by which the system compensates for the mismatch in charge density.

Very interestingly, we have found that controlling the degree of overcharging of the lipid-protein nanotube enables us to switch between two states of nanotubes,” stated Safinya. “With either open ends (negative overcharged), or closed ends (positive overcharged with lipid caps), these nanotubes could form the basis for controlled chemical and drug encapsulation and release.”

In the experiments, the diameter of the inside area of the nanotube is around 16 nm (a nanometer is a billionth of a meter). The diameter of the entire capsule is around 40 nm.

According to Raviv, the drug Taxol is a chemotherapy drug that could be delivered using these nanotubes. Taxol is already being used by the researchers to lengthen and stabilize the lipid-protein nanotubes.

The study was carried out using the combination of sophisticated synchrotron X-ray scattering methods at the Stanford Synchrotron Radiation Laboratory (SSRL) and advanced electron microscopy at UCSB.

The National Institutes of Health and the National Science Foundation (NSF) provided the funds for this research. US Department of Energy (DoE) supports the SSRL. The International Human Frontier Science Program and the European Molecular Biology Organization also supported Raviv.

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