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  • What allows particles to enter cells may surprise you

Aug 2008
David L. Shenkenberg

For years, scientists have been coming up with ways to make drugs, particularly highly toxic chemotherapy treatments, safer for patients. It would revolutionize medicine if the drugs could be packaged such that they keep the healthy parts of the body safe and enter only the cells of the tumor or other locations of the disease.

But getting drugs into cells is not easy. Sometimes researchers have used heat or mild electricity to induce transient pores in the cell membrane so that the drug can pass through, but this strategy damages cells. At other times, the cell takes in the drug but expels it as waste, so it does no good.

Many biological molecules enter cells readily, so to help the particles enter cells, most scientists have appended biological molecules onto synthetic drug coatings. Nobody fully understands how these biological materials enter cells, and no one has developed a totally synthetic material that can do the same … until now.

Researchers at MIT in Cambridge, Mass., have created the first fully synthetic material that can do it. They coated gold nanoparticles with alternating bands, or stripes, of two types of molecules: sulfonate and methyl groups. The choice of nanoparticles of gold was apt because they have been used to ameliorate arthritis and are being explored for treating cancer. The scientists carried out confocal fluorescence microscopy to see whether these stripes help particles enter cells. To do that, they attached a few molecules of highly fluorescent “bodipy” dye to the surface of the particles.

Researchers created the first totally synthetic particles to enter cells seamlessly. They were labeled with a red fluorescent dye and tracked microscopically. Courtesy of Francesco Stellacci, Darrell J. Irvine and others.

They found that the striped particles could enter cells without even creating transient holes in the cell membrane — much less rupturing the cells — because the particles are coated with material similar to that of the cell membrane. Team member Darrell J. Irvine likened the effect to a science experiment a kid can do. He explained that, if a child pokes a soap bubble with a wand, the bubble will pop. But if the wand is coated with soap, it will pass through the bubble without breaking it.

Additionally, the striped particles did not bind to random proteins in the cell, did not agglomerate and were not expelled as waste, all of which are favorable results. The scientists hope to continue investigating cell penetration and using the results to develop new coatings that make drugs safer for the body.

It’s also notable that Irvine has recently earned an extremely prestigious Howard Hughes Medical Institute investigator fellowship, which carries with it a substantial monetary award.

Nature Materials, July 2008, pp. 588-595.

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