Bio-nanotubes Developed; May Help in Drug Delivery

Source: University of California, Santa Barbara
http://www.ia.ucsb.edu/pa/display.aspx?pkey=1325

'Smart' Bio-nanotubes Developed; May Help in Drug Delivery

August 2, 2005

(Santa Barbara, Calif.) – Materials scientists working with biologists at
the University of California, Santa Barbara have developed "smart"
bio-nanotubes — with open or closed ends — that could be developed for drug
or gene delivery applications.

The nanotubes are "smart" because in the future they could be designed to
encapsulate and then open up to deliver a drug or gene in a particular
location in the body. The scientists found that by manipulating the
electrical charges of lipid bilayer membranes and microtubules from cells,
they could create open or closed bio-nanotubes, or nanoscale capsules. The
news is reported in an article to be published in the August 9 issue of the
Proceedings of the National Academy of Sciences. It is currently available
on-line in the PNAS Early Edition. See:
http://www.pnas.org/cgi/content/abstract/0502183102v1

The findings resulted from a collaboration between the laboratories of
Cyrus R. Safinya, professor of materials and physics and faculty member of
the Molecular, Cellular, and Developmental Biology Department, and Leslie
Wilson, professor of biochemistry in the Department of Molecular, Cellular
and Developmental Biology and the Biomolecular Science and Engineering
Program. The first author of the article is Uri Raviv, a post-doctoral
researcher in Safinya's lab and a fellow of the International Human
Frontier Science Program Organization. The other co-authors are Daniel J.
Needleman, formerly Safinya's graduate student who is now a postdoctoral
fellow at Harvard Medical School; Youli Li, researcher in the Materials
Research Laboratory; and Herbert P. Miller, staff research associate in the
Department of Molecular, Cellular and Developmental Biology.

The scientists used microtubules purified from the brain tissue of a cow
for their experiments. Microtubules are nanometer-scale hollow cylinders
derived from the cell cytoskeleton. In an organism, microtubules and their
assembled structures are critical components in a broad range of cell
functions –– from providing tracks for the transport of cargo to forming
the spindle structure in cell division. Their functions include the
transport of 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," said Safinya.

Raviv explained, "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."

They used the example 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 the charge.

The new type of self-assembly arises because of an extreme mismatch between
the charge densities of microtubules and cationic lipid, explained Raviv.
"This is a novel finding in equilibrium self-assembly," he said.

The nanotubule consisting of a three-layer wall appears to be the way the
system compensates for this charge density mismatch, according to the authors.

"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," said 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."

The inner space of the nanotube in these experiments measures about 16
nanometers in diameter. (A nanometer is a billionth of a meter.) The whole
capsule is about 40 nanometers in diameter.

Raviv explained that the chemotherapy drug Taxol is one type of drug that
could be delivered with these nanotubes. The scientists are already using
Taxol in their experiments to stabilize and lengthen the lipid-protein
nanotubes.

The work was performed using state-of-the-art synchrotron x-ray scattering
techniques at the Stanford Synchrotron Radiation Laboratory (SSRL),
combined with sophisticated electron microscopy at UCSB. The work was
funded by the National Institutes of Health and the National Science
Foundation. SSRL is supported by the U.S. Department of Energy. Raviv was
also supported by the International Human Frontier Science Program and the
European Molecular Biology Organization.

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† About the Illustration

"Smart" bionanotubes. Lipid protein nanotubes made of microtuble protein
(made of tubulin protein subunits shown as red-blue-yellow-green objects)
that is coated by a lipid bilayer (drawn with yellow tails and green and
white spherical heads) which in turn is coated by tubulin protein rings or
spirals. By controlling the relative amount of lipid and protein it is
possible to switch between two states of nanotubes with either open ends
(shown in the center) or closed ends with lipid caps (shown on the left), a
process which forms the basis for controlled chemical and drug
encapsulation and release. A top view of the nanotubes and a magnified
region is shown on the right. The image was created by Peter Allen.

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