Michigan University. US: By making what might be the world's smallest three-dimensional
unofficial Block "M," University of Michigan researchers have
demonstrated a nanoparticle manufacturing process capable of producing
multilayered, precise shapes. The researchers say their technique may pave the way to medications
that can target specific cells, deliver multiple drugs at different
times and rates, and even allow doctors to steer the drugs to particular
locations in the body.
They could also offer researchers better ways to
test new therapies.
The new method produces particles that can be 10 or more layers
thick—to incorporate several courses of drug treatments, metals,
plastics or virtually any other material. They can be made in precisely
controlled sizes and shapes as small as 25 nanometers across. At
115-by-160 microns and 3 microns thick, the mock Michigan logos are each
about the size of a grain of sand. A micron, or micrometer, is
one-thousandth of a millimeter.
"The Block 'M's' were a test," said Anish Tuteja, U-M assistant
professor of materials science and engineering and a developer of the
process. "This opens up all sorts of opportunities for combining
different polymers and molecules in a variety of shapes. And because
it's simple and low-cost, we can explore new possibilities much more
easily than in the past."
Researchers say one of the first applications could be in
chemotherapy, where their ability to incorporate several layers could
enable drug makers to combine different chemotherapy drugs and target
multiple types of cancer cells with a single treatment. They could also
layer in magnetic materials that enable doctors to steer the drugs
toward tumors.
Another key trait is the particles' flexible shape, size and makeup,
which may enable doctors and drug makers to optimize medications to more
effectively target cancer cells and do less damage to healthy cells.
"Different types of cancer have different cell structures, and each
type can internalize nanoparticles in a different way," said Geeta
Mehta, U-M assistant professor of materials science and engineering, who
is working on the project. "We can easily tailor the shape and drug
combinations of these new particles to each type of cancer so that
they're more effective against cancerous cells and less harmful to
healthy cells."
While any new treatment is likely five-to-10 years out, the team
hopes to have an early iteration of the medications available for
testing within one to two years.
The particles' versatility and relatively simple production process
also makes them useful in the lab for testing new treatments, and for
gaining a better understanding of exactly how medications interact with
cells.
"The University of Michigan has an extensive library of new cancer
drugs in development, and I think these particles are going to help us
understand how to use them most effectively," Mehta said. "We can easily
try new combinations of drugs and different particle shapes, and we can
include dyes and other markers to see how they behave inside a cell."
The particles may be useful for other drug delivery applications as
well, including inhalable vaccines and time-release prescription drugs
that could be taken far less frequently than current medications.
While
researchers have successfully created multilayered nanoparticles in the
past, these particles are the first to combine that capability with
precise control over the particles' shape, size and composition.
The research team began the production process with a silicon wafer
that has a liquid-repellent coating. They used ultraviolet light to etch
away the coating in the shape of the final particles. Finally, they
dipped the etched wafer into a liquid containing their polymer dissolved
in a solvent. The liquid settled only on the etched areas, and when the
solvent evaporated, the polymer remained, leaving precisely shaped
nanoparticles. To get multiple layers, researchers simply dipped the
wafer again and again, forming a new layer each time.
Tuteja said current methods for manufacturing multilayered
nanoparticles are more complex than the new approach. Most can only
produce spherical particles, and controlling particle size is difficult.
He said the team is in the process of developing automated
manufacturing methods that could eventually produce larger numbers of
particles with greater efficiency. The process could potentially be used
to manufacture particles for a variety of applications including
computer displays, diagnostic sensors and even microscopic motors.
Mehta is also an assistant professor of biomedical engineering and
macromolecular science and engineering. Tuteja is also an assistant
professor of macromolecular science and engineering.
A paper on the technique, titled "Wettability Engendered Templated
Self-Assembly (WETS) for Fabricating Multiphasic Particles," is
published in the Feb. 25 issue of ACS Applied Materials & Interfaces
magazine. Research was supported by the National Science Foundation and
the Office of Naval Research.