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Rapid Nano Molding

Researchers are using a new all-purpose nano synthesis method to design cancer-fighting nanoparticles.
March 29, 2006

A highly versatile method for making nanoparticles has now been used to make multipurpose cancer treatment particles. According to Joseph DeSimone, chemistry and chemical engineering professor at the University of North Carolina at Chapel Hill and North Carolina State University, who presented the work at the American Chemical Society conference this week in Atlanta, the new synthesis method has potential applications in fuel cells, microfluidics, and vaccines as well.

[For images of the nano-molding method, click here.] 

The process has the “ability to create nanoparticles of nearly any shape or chemical composition. It is very, very promising,” says Shelton Earp, director of the Lineberger Comprehensive Cancer Center at UNC. Experts at the cancer center are now starting live animal tests of nanoparticles that were made using the method. The particles are designed to slip out of the bloodstream and deliver both drugs and imaging agents directly to cancer cells, sparing healthy cells. Such targeted delivery could significantly improve both the safety and effectiveness of cancer drugs. Earp says that within a year, separate studies will show whether particles made this way can safely and effectively combat skin and breast cancer in mice.

Researchers led by DeSimone created the nanoparticles out of a polymer and a cancer drug such as doxorubicin, forming 200 nanometer-sized particles – about the size of some viruses. Then they attached monoclonal antibodies that link to proteins prevalent in cancer cells, enabling targeted drug delivery. Imaging agents can also be attached to the outside of the particle, potentially allowing doctors to monitor where the drug is going. The polymer, which is the same material used in bio-absorbable sutures, should eventually break down and leave the body.

Several other research groups are now developing and testing nanoparticles for drug delivery. What sets this effort apart is the versatile molding method used to make the particles, which Robert Langer, chemical engineering professor at MIT, says is “quite impressive.” The method allows researchers to make very small and precisely controlled shapes out of organic materials, including ones known to be safe in the body.

As with any molding processes, DeSimone’s method begins with an original shape, called the “master,” that someone wants to copy. A material is then formed around this shape – this becomes the mold. The master is removed, and another material introduced, which is formed by the mold into a replica of the original shape. At the heart of this new nano method is a material for making molds called perfluoropolyether (PFPE), which starts as a liquid with the extraordinary ability to slip into every nook and cranny of the master without sticking to it. The researchers then convert the polymer into a flexible solid by exposing it to light, and remove the master – an easy step because the mold does not stick to the original and is flexible.

The researchers have used nanotubes and virus particles as masters, for example, and made copies of them with a resolution down to half a nanometer. For the drug-delivery particles, they made the master out of silicon, using lithography techniques, making a series of disc shapes on a wafer. They then poured PFPE over the disks and cured them to form a mold. To make replicas of the discs, they pressed the mold into another liquid poured onto a flat surface. This liquid filled the mold, then was cured to form solid replicas of the original disks. Using lithography brings control over the size and shape, says DeSimone, with the “precision and uniformity of the electronics industry.”

Larken Euliss, a chemist at UNC who works with DeSimone, says recent research shows that differences in size and shape matter when it comes to effectively delivering drugs to cells. Their methods could lead to more effective drug-delivery structures, which tend now to be spherical. A cigar-shaped particle, for example, could be thin enough to escape through the wall of a blood vessel, and so reach a tumor, and it’s long shape would let researcher load more drug cargo.

Drug delivery particles are just one application. Zhilian Zhou, a researcher working with DeSimone, has developed a fuel cell with significantly higher performance than current ones, in part, using the molding method to pattern a key membrane.

Ultimately, DeSimone would like to take advantage of the synthesis method’s ability to form copies of viruses to make emergency “vaccines.” He’s already been able to make copies of viruses, but these copies do not have the same chemical composition as viruses, and so won’t link to cells like viruses do. DeSimone says it should be possible to incorporate active molecules into the molding process, though, and thereby create “artificial viruses” that can bind to cells and block real viruses from doing so. And since the virus copies have no DNA, they would not be dangerous, he says.

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